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A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease (Scarlet Road)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01224106
Recruitment Status : Completed
First Posted : October 19, 2010
Results First Posted : December 13, 2021
Last Update Posted : December 13, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: Gantenerumab
Drug: Placebo
Enrollment 799
Recruitment Details The study was conducted at 128 centers in 24 countries.
Pre-assignment Details A total of 799 participants were randomised in this study. Of these, a total of 797 participants were enrolled and received at least one dose of any study drug and represented the Safety population during the Double-Blind Treatment Phase (Parts 1 and 2 of the study). From the Double-Blind Treatment Phase, a total of 154 participants (at 53 sites) were enrolled into Open-Label Extension (OLE) Phase (Part 3 of the study).
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years. Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Period Title: Double-Blind Treatment Phase
Started 266 271 260 0 0
Completed 187 185 180 0 0
Not Completed 79 86 80 0 0
Reason Not Completed
Death             3             0             0             0             0
Physician Decision             6             5             4             0             0
Adverse Event             0             5             3             0             0
Other             0             0             1             0             0
Participant/legal guardian decision             7             8             8             0             0
Parts 1 and 2 Termination by Sponsor             62             68             63             0             0
Lost to Follow-up             1             0             1             0             0
Period Title: Open-Label Extension (OLE) Phase
Started 0 0 0 49 105
Completed 0 0 0 33 71
Not Completed 0 0 0 16 34
Reason Not Completed
Death             0             0             0             1             3
Adverse Event             0             0             0             2             6
Physician Decision             0             0             0             2             7
Withdrawal by Subject             0             0             0             6             15
Other             0             0             0             5             3
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) Total
Hide Arm/Group Description Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years. Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years. Total of all reporting groups
Overall Number of Baseline Participants 266 271 260 49 105 951
Hide Baseline Analysis Population Description
A total of 797 participants were enrolled into the Double-Blind Treatment phase of this study and the entire study. A subset (154) of these participants moved into the OLE phase of this study.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
69.5  (7.5) 70.3  (7.0) 71.3  (7.1) 70.4  (7.2)
[1]
Measure Description: Parts 1 and 2 of the study.
[2]
Measure Analysis Population Description: Participants in the Double-Blind Treatment Phase of this study.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 0 participants 0 participants 0 participants 49 participants 105 participants 154 participants
75.5  (5.8) 73.7  (7.3) 74.3  (6.9)
[1]
Measure Description: Part 3 of the study.
[2]
Measure Analysis Population Description: Participants in the OLE Phase of this study.
Sex: Female, Male   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
Female
149
  56.0%
152
  56.1%
152
  58.5%
 0 0
453
  56.8%
Male
117
  44.0%
119
  43.9%
108
  41.5%
 0 0
344
  43.2%
[1]
Measure Description: Parts 1 and 2 of the study.
[2]
Measure Analysis Population Description: Participants in the Double-Blind Treatment Phase of this study.
Sex: Female, Male   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 49 participants 105 participants 154 participants
Female 0 0 0
27
  55.1%
64
  61.0%
91
  59.1%
Male 0 0 0
22
  44.9%
41
  39.0%
63
  40.9%
[1]
Measure Description: Part 3 of the study.
[2]
Measure Analysis Population Description: Participants in the OLE Phase of this study.
Race/Ethnicity, Customized   [1] [2] 
Measure Type: Number
Unit of measure:  Participants
Non-Hispanic Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
217 221 210 648
Hispanic Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
41 39 47 127
American Indian or Alaska native Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
1 6 5 12
Asian Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
9 4 7 20
Black Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
1 2 2 5
White Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
239 252 239 730
Not Available Number Analyzed 266 participants 271 participants 260 participants 0 participants 0 participants 797 participants
24 18 10 52
[1]
Measure Description: Parts 1 and 2 of the study.
[2]
Measure Analysis Population Description: Participants in the Double-Blind Treatment Phase of this study.
Race/Ethnicity, Customized   [1] [2] 
Measure Type: Number
Unit of measure:  Participants
Non-Hispanic Number Analyzed 0 participants 0 participants 0 participants 49 participants 105 participants 154 participants
39 88 127
Hispanic Number Analyzed 0 participants 0 participants 0 participants 49 participants 105 participants 154 participants
10 17 27
American Indian or Alaska native Number Analyzed 0 participants 0 participants 0 participants 49 participants 105 participants 154 participants
0 3 3
Asian Number Analyzed 0 participants 0 participants 0 participants 49 participants 105 participants 154 participants
2 0 2
White Number Analyzed 0 participants 0 participants 0 participants 49 participants 105 participants 154 participants
42 101 143
Unknown Number Analyzed 0 participants 0 participants 0 participants 49 participants 105 participants 154 participants
5 1 6
[1]
Measure Description: Part 3 of the study.
[2]
Measure Analysis Population Description: Participants in the OLE Phase of this study.
1.Primary Outcome
Title Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase)
Hide Description The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 104 105 100
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
1.19  (1.68) 1.41  (2.02) 1.47  (1.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6744
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect Size
Estimated Value -0.044
Confidence Interval (2-Sided) 95%
-0.248 to 0.161
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4494
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect Size
Estimated Value -0.085
Confidence Interval (2-Sided) 95%
-0.304 to 0.135
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase)
Hide Description An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame Baseline up until a maximum of 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 49 105
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
46
  93.9%
100
  95.2%
SAEs
18
  36.7%
28
  26.7%
3.Secondary Outcome
Title Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)
Hide Description The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 105 104 100
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
3.68  (6.64) 3.52  (6.28) 3.97  (6.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7458
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect Size
Estimated Value 0.035
Confidence Interval (2-Sided) 95%
-0.179 to 0.250
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.723
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect Size
Estimated Value 0.042
Confidence Interval (2-Sided) 95%
-0.191 to 0.275
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)
Hide Description Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 91 95 91
Median (95% Confidence Interval)
Unit of Measure: Days
63.64
(56.63 to 69.82)
62.98
(56.00 to 69.16)
70.64
(63.34 to 76.75)
5.Secondary Outcome
Title Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)
Hide Description The Cambridge Neuropsychological Test Automated Battery (CANTAB) ® is a cognitive test battery that incorporates a variety of executive and memory tasks in order to assess neuropsychological function. The end outcome as reported below, is a Z-Composite Score. The score range of the Z-Composite Score is from (-) infinity to (+) infinity with a score of zero representing the population mean, lower (negative) scores representing poorer cognitive outcomes and higher (positive) scores representing better cognitive outcomes.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 90 87 80 73
Mean (Standard Deviation)
Unit of Measure: Z-Score
-1.72  (2.99) -1.37  (2.74) -1.4  (3.11) -1.93  (3.08)
6.Secondary Outcome
Title Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)
Hide Description FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words*4. The minimum score is 0 (worse).
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 100 102 97 79
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
-4.05  (8.73) -4.11  (8.57) -6.42  (8.45) -4.05  (8.68)
7.Secondary Outcome
Title Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)
Hide Description Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 105 104 99 84
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
3.59  (4.93) 4.89  (6.2) 4.03  (5.75) 3.6  (4.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0825
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect Size
Estimated Value -0.191
Confidence Interval (2-Sided) 95%
-0.407 to 0.025
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7171
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Effect Size
Estimated Value 0.043
Confidence Interval (2-Sided) 95%
-0.19 to 0.276
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)
Hide Description The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 104 105 100 83
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
0.1  (0.29) 0.18  (0.36) 0.14  (0.33) 0.1  (0.31)
9.Secondary Outcome
Title Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)
Hide Description The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 103 105 99 82
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
0.6  (3.22) 0.39  (2.57) 0.34  (2.84) 0.72  (3.35)
10.Secondary Outcome
Title Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase)
Hide Description CSF biomarker phospho-tau (p-tau) is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 72 71 66 56
Mean (Standard Deviation)
Unit of Measure: Percentage Change
p-tau (Week 104) Number Analyzed 72 participants 71 participants 66 participants 56 participants
2.77  (20.69) -4.78  (11.9) -7.34  (10.09) 2.84  (23.19)
t-tau (Week 104) Number Analyzed 72 participants 71 participants 66 participants 56 participants
3.43  (19.95) -1.36  (12.89) -2.12  (11.01) 3.46  (22.32)
Abeta (Week 104) Number Analyzed 69 participants 64 participants 65 participants 56 participants
4.87  (36.14) 2.45  (24.57) 15.2  (45.24) 4.3  (39.31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
Comments Statistical analysis of the Abeta 1-42 CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9734
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
Comments Statistical analysis of the Abeta 1-42 CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0629
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
Comments Statistical analysis of the p-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0084
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
Comments Statistical analysis of the p-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 105 mg (Parts 1 and 2)
Comments Statistical analysis of the t-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 105 mg (Parts 1 and 2)" treatment arms at Week 104.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0903
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo (Parts 1 and 2), Gantenerumab 225 mg (Parts 1 and 2)
Comments Statistical analysis of the t-tau CSF biomarker between "Placebo (Parts 1 and 2)" and "Gantenerumab 225 mg (Parts 1 and 2)" treatment arms at Week 104.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0434
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
11.Secondary Outcome
Title Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase)
Hide Description Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 131 124 119 107
Mean (Standard Deviation)
Unit of Measure: Percentage Change
HRV (Week 104) -7.61  (4.03) -7.52  (3.96) -7.34  (3.84) -7.7  (4.01)
HLV (Week 104) -7.8  (4.28) -7.76  (3.74) -7.27  (3.78) -8.12  (4.19)
12.Secondary Outcome
Title Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase)
Hide Description The different regions of the brain that were analyzed included cerebellum gray, whole cerebellum, composite white matter, subcortical white matter, pons and composite reference.
Time Frame Baseline, Week 156
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo Match Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 6 4 10 4
Mean (Standard Deviation)
Unit of Measure: Percentage Change
Cerebellum gray (Week 156) 6.26  (9.1) 2.7  (10.59) -8.36  (9.11) 5.95  (11.13)
Whole Cerebellum (Week 156) 5.41  (7.13) 2.07  (8.65) -8.44  (8.06) 5.17  (8.66)
Composite White Matter (Week 156) 2.75  (3.18) -0.87  (2.95) -4.86  (6.35) 3.07  (2.07)
Subcortical White Matter (Week 156) 4.83  (4.95) 1.69  (4.45) -0.42  (8.26) 4.59  (0.55)
Pons (Week 156) 1.72  (2.51) -2.83  (3.39) -6.99  (5.65) 2.1  (2.73)
Composite Reference (Week 156) 4.5  (3.48) 1.19  (5.63) -6.75  (6.1) 4.46  (4.49)
13.Secondary Outcome
Title Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase)
Hide Description The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Time Frame Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis and note that participants who received dose reduction were excluded from this PK analysis.
Arm/Group Title Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 239 227
Mean (Standard Deviation)
Unit of Measure: µg/ml (micrograms per milliliter)
Week 1 (Post-Dose) Number Analyzed 239 participants 227 participants
3.56  (2.36) 7.4  (4.28)
Week 8 (Pre-Dose) Number Analyzed 237 participants 225 participants
2.87  (1.84) 5.92  (3.16)
Week 20 (Pre-Dose) Number Analyzed 228 participants 220 participants
3.7  (2.15) 7.66  (4.14)
Week 44 (Pre-Dose) Number Analyzed 212 participants 199 participants
4.08  (2.44) 8.22  (4.51)
Week 53 (Post-Dose) Number Analyzed 195 participants 185 participants
6.77  (3.94) 15  (9.34)
Week 68 (Pre-Dose) Number Analyzed 165 participants 155 participants
3.95  (2.35) 8.91  (4.86)
Week 100 (Pre-Dose) Number Analyzed 98 participants 86 participants
4.35  (2.34) 9.4  (4.69)
Week 101 (Post-Dose) Number Analyzed 95 participants 77 participants
7.32  (3.53) 16.63  (7.96)
14.Secondary Outcome
Title Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)
Hide Description The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Time Frame Baseline, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 104 105 99
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
-2.31  (3.23) -2.46  (3.68) -2.25  (3.31)
15.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase)
Hide Description An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame Baseline up until a maximum of 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of study drug, regardless of whether the participant withdrew prematurely or not. All safety data was analyzed according to study drug actually received.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 266 271 260
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
250
  94.0%
241
  88.9%
240
  92.3%
SAEs
55
  20.7%
48
  17.7%
46
  17.7%
16.Secondary Outcome
Title Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase)
Hide Description Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Gantenerumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Time Frame Baseline up until a maximum of 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of study drug, regardless of whether the participant withdrew prematurely or not. All safety data was analyzed according to study drug actually received. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2)
Hide Arm/Group Description:
Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Overall Number of Participants Analyzed 259 266 256
Measure Type: Number
Unit of Measure: Percentage of Participants
Baseline ADAs Number Analyzed 259 participants 266 participants 256 participants
5.8 7.5 5.5
Treatment Emergent ADAs Number Analyzed 259 participants 258 participants 250 participants
5.0 7.0 6.4
17.Secondary Outcome
Title Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)
Hide Description The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.
Time Frame Baseline, Week 156
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 21 51
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
5.8  (7.3) 8.9  (9.7)
18.Secondary Outcome
Title Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)
Hide Description The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.
Time Frame Baseline, Week 156
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 21 52
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
3.3  (2.4) 2.8  (3.0)
19.Secondary Outcome
Title Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)
Hide Description The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. The score range for ADAS-Cog-13 is from 0 to 85 with higher scores representing severe dysfunction.
Time Frame Baseline, Week 156
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 21 51
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
8.0  (8.2) 10.4  (10.6)
20.Secondary Outcome
Title Time to Onset of Dementia at Week 156 (OLE Phase)
Hide Description Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.
Time Frame Baseline, Week 156
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 3 14
Median (95% Confidence Interval)
Unit of Measure: Days
38.18
(9.90 to 66.97)
50.82
(32.04 to 66.87)
21.Secondary Outcome
Title Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)
Hide Description FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words*4. The minimum score is 0 (worse).
Time Frame Baseline, Week 156
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Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 22 51
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
-7.7  (9.3) -4.1  (8.3)
22.Secondary Outcome
Title Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)
Hide Description Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.
Time Frame Baseline, Week 156
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Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 22 52
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
8.1  (5.3) 6.8  (6.8)
23.Secondary Outcome
Title Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)
Hide Description The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.
Time Frame Baseline, Week 156
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 21 52
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
0.6  (0.6) 0.5  (0.6)
24.Secondary Outcome
Title Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase)
Hide Description Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 152 using magnetic resonance imaging.
Time Frame Baseline, Week 152
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 18 51
Mean (Standard Deviation)
Unit of Measure: Percentage Change
HRV (Week 152) 16.7  (8.4) 16.1  (8.2)
HLV (Week 152) 16.2  (13.0) 18.0  (8.9)
25.Secondary Outcome
Title Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase)
Hide Description The regions of the brain that were analyzed included cerebellum gray and composite reference.
Time Frame Baseline, Week 156
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: Percentage Change
Cerebellum gray (Week 156) -0.2  (0.2)
Composite Reference (Week 156) -41.4  (29.9)
26.Secondary Outcome
Title Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase)
Hide Description The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.
Time Frame Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis and note that participants who received dose reduction were excluded from this PK analysis.
Arm/Group Title Gantenerumab 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at a dose of 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 99
Mean (Standard Deviation)
Unit of Measure: µg/ml (micrograms per milliliter)
Week 64 (Pre-Dose) Number Analyzed 99 participants
33.0  (21.7)
Week 100 (Pre-Dose) Number Analyzed 89 participants
39.2  (22.7)
Week 101 (Post-Dose) Number Analyzed 88 participants
80.5  (37.8)
Week 104 (Pre-Dose) Number Analyzed 91 participants
40.5  (22.5)
Week 136 (Pre-Dose) Number Analyzed 83 participants
45.2  (22.4)
Week 156 (Pre-Dose) Number Analyzed 93 participants
39.6  (28.2)
Week 208 (Pre-Dose) Number Analyzed 26 participants
37.1  (29.2)
27.Secondary Outcome
Title Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)
Hide Description The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.
Time Frame Baseline, Week 156
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 22 53
Mean (Standard Deviation)
Unit of Measure: Scores on a Scale
-4.3  (4.3) -4.7  (4.6)
28.Secondary Outcome
Title Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase)
Hide Description Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Time Frame Baseline up until a maximum of 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.
Arm/Group Title Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description:
Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Overall Number of Participants Analyzed 49 104
Measure Type: Number
Unit of Measure: Percentage of Participants
Baseline ADAs Number Analyzed 49 participants 104 participants
2.0 5.8
Treatment Emergent ADAs Number Analyzed 46 participants 102 participants
2.2 2.9
Time Frame Baseline up until a maximum of 9.5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Hide Arm/Group Description Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2. Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years. Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
All-Cause Mortality
Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/266 (2.26%)      0/271 (0.00%)      2/260 (0.77%)      1/49 (2.04%)      3/105 (2.86%)    
Hide Serious Adverse Events
Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   55/266 (20.68%)      48/271 (17.71%)      46/260 (17.69%)      18/49 (36.73%)      28/105 (26.67%)    
Blood and lymphatic system disorders           
Anaemia * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Iron deficiency anaemia * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Cardiac disorders           
Acute myocardial infarction * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Arrhythmia * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Atrial flutter * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Bradycardia * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Cardiac failure * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Mitral valve incompetence * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Myocardial infarction * 1  2/266 (0.75%)  2 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Supraventricular tachycardia * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Acute coronary syndrome * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Angina pectoris * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Angina unstable * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Arteriosclerosis coronary artery * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Atrial fibrillation * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Atrial thrombosis * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Atrioventricular block second degree * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Cardiac ventricular thrombosis * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Coronary artery disease * 1  0/266 (0.00%)  0 2/271 (0.74%)  2 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Myocardial rupture * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Sinus arrest * 1  1/266 (0.38%)  1 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Ear and labyrinth disorders           
Deafness unilateral * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Endocrine disorders           
Diabetes insipidus * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Eye disorders           
Retinal detachment * 1  0/266 (0.00%)  0 2/271 (0.74%)  2 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Visual impairment * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Gastrointestinal disorders           
Constipation * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Gastric haemorrhage * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Gastric ulcer * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Inguinal hernia * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Intestinal obstruction * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Abdominal distension * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Abdominal pain * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Diarrhoea * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Diverticulum intestinal haemorrhagic * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Gastritis * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Hiatus hernia * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Pancreatic mass * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Umbilical hernia * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
General disorders           
Asthenia * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Chest pain * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Gait disturbance * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Sudden death * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Device dislocation * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Malaise * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Pain * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Pyrexia * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Hepatobiliary disorders           
Cholecystitis * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Cholelithiasis * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Immune system disorders           
Anaphylactic reaction * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Type I hypersensitivity * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Infections and infestations           
Abdominal abscess * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Atypical pneumonia * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
COVID-19 * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Diverticulitis * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Infection * 1  0/266 (0.00%)  0 1/271 (0.37%)  2 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Lower respiratory tract infection * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Otitis media * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Pelvic abscess * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Respiratory tract infection * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Sepsis * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Urinary tract infection * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Appendicitis * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Bacterial sepsis * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Cellulitis * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Cholecystitis infective * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Cystitis * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Erysipelas * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Gastroenteritis * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Gastroenteritis viral * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Lyme disease * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Pleural infection bacterial * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Pneumonia * 1  1/266 (0.38%)  1 1/271 (0.37%)  1 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Post procedural infection * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Subcutaneous abscess * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Injury, poisoning and procedural complications           
Fall * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 2/49 (4.08%)  2 4/105 (3.81%)  4
Femoral neck fracture * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Head injury * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Hip fracture * 1  1/266 (0.38%)  1 1/271 (0.37%)  1 2/260 (0.77%)  2 1/49 (2.04%)  1 0/105 (0.00%)  0
Joint injury * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Lumbar vertebral fracture * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Muscle strain * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Pelvic fracture * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Post lumbar puncture syndrome * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Procedural pain * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Rib fracture * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Subdural haematoma * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 1/105 (0.95%)  1
Subdural haemorrhage * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Upper limb fracture * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Ankle fracture * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Femur fracture * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Humerus fracture * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Laceration * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Ligament rupture * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Lower limb fracture * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Meniscus injury * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Post procedural haematuria * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Radiation mucositis * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Radius fracture * 1  2/266 (0.75%)  2 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Road traffic accident * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Spinal fracture * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Tibia fracture * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Urinary retention postoperative * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Investigations           
Body temperature increased * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Blood pressure increased * 1  0/266 (0.00%)  0 1/271 (0.37%)  4 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
C-reactive protein increased * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Metabolism and nutrition disorders           
Dehydration * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Diabetes mellitus * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Musculoskeletal and connective tissue disorders           
Osteitis * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Osteoarthritis * 1  1/266 (0.38%)  1 1/271 (0.37%)  1 1/260 (0.38%)  1 1/49 (2.04%)  1 0/105 (0.00%)  0
Pain in extremity * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Arthritis reactive * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Rotator cuff syndrome * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Spinal column stenosis * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Adenocarcinoma of colon * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Biliary cancer metastatic * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Breast cancer * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Colon cancer * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 1/260 (0.38%)  1 1/49 (2.04%)  1 0/105 (0.00%)  0
Laryngeal squamous cell carcinoma * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Leukaemia * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Lung cancer metastatic * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Lung neoplasm malignant * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 1/105 (0.95%)  1
Metastases to bone * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Myelodysplastic syndrome * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Plasmacytoma * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Prostate cancer * 1  2/266 (0.75%)  2 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Small cell carcinoma * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Basal cell carcinoma * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Benign ovarian tumour * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Bladder cancer * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Bladder transitional cell carcinoma * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Bone sarcoma * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Breast cancer stage II * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Gastrointestinal tract adenoma * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Glioma * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Intestinal adenocarcinoma * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Intraductal proliferative breast lesion * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Pharyngeal neoplasm benign * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Rectal adenocarcinoma * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Renal cell carcinoma * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Renal oncocytoma * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Tongue neoplasm malignant stage unspecified * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Nervous system disorders           
ARIA-E * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 2/105 (1.90%)  2
Balance disorder * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Cerebellar infarction * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Cerebral haematoma * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Cerebral haemorrhage * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 1/49 (2.04%)  1 0/105 (0.00%)  0
Dementia with Lewy bodies * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Epilepsy * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 2/105 (1.90%)  2
Generalised tonic-clonic seizure * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Headache * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Neuropathy peripheral * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Partial seizures * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Retrograde amnesia * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Seizure * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Speech disorder * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Subarachnoid haemorrhage * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Thalamic infarction * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Amyotrophic lateral sclerosis * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Ischaemic stroke * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 2/260 (0.77%)  2 0/49 (0.00%)  0 0/105 (0.00%)  0
Monoparesis * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Presyncope * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Radial nerve palsy * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Syncope * 1  2/266 (0.75%)  2 1/271 (0.37%)  1 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Transient global amnesia * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Transient ischaemic attack * 1  1/266 (0.38%)  1 1/271 (0.37%)  1 2/260 (0.77%)  2 0/49 (0.00%)  0 0/105 (0.00%)  0
Dizziness * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Psychiatric disorders           
Agitation * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Confusional state * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 3/105 (2.86%)  3
Delusion * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Neuropsychiatric symptoms * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Suicidal behaviour * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 1/105 (0.95%)  1
Anxiety * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Behavioral and psychological symptoms of dementia * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Depression * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Major depression * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Suicide attempt * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Renal and urinary disorders           
Bladder obstruction * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Haematuria * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Reproductive system and breast disorders           
Prostatomegaly * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 2/260 (0.77%)  2 0/49 (0.00%)  0 0/105 (0.00%)  0
Benign prostatic hyperplasia * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Cystocele * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Ovarian cyst * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Delirium * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Haemothorax * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Pulmonary embolism * 1  1/266 (0.38%)  1 1/271 (0.37%)  1 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Surgical and medical procedures           
Rotator cuff repair * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Urethral caruncle removal * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Hip arthroplasty * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Knee arthroplasty * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Spinal decompression * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Urethral dilation procedure * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Vascular disorders           
Deep vein thrombosis * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 1/260 (0.38%)  1 0/49 (0.00%)  0 0/105 (0.00%)  0
Peripheral artery aneurysm * 1  0/266 (0.00%)  0 1/271 (0.37%)  1 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Peripheral ischaemia * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 0/105 (0.00%)  0
Hypotension * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
Malignant hypertension * 1  1/266 (0.38%)  1 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 0/105 (0.00%)  0
1
Term from vocabulary, MedDRA 23.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (Parts 1 and 2) Gantenerumab 105 mg (Parts 1 and 2) Gantenerumab 225 mg (Parts 1 and 2) Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   163/266 (61.28%)      188/271 (69.37%)      189/260 (72.69%)      40/49 (81.63%)      87/105 (82.86%)    
Eye disorders           
Cataract * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 4/49 (8.16%)  5 2/105 (1.90%)  3
Gastrointestinal disorders           
Diarrhoea * 1  13/266 (4.89%)  18 15/271 (5.54%)  22 15/260 (5.77%)  18 3/49 (6.12%)  3 11/105 (10.48%)  14
Vomiting * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 5/49 (10.20%)  5 6/105 (5.71%)  9
General disorders           
Injection site erythema * 1  3/266 (1.13%)  3 29/271 (10.70%)  133 35/260 (13.46%)  114 17/49 (34.69%)  196 36/105 (34.29%)  359
Fatigue * 1  8/266 (3.01%)  8 7/271 (2.58%)  7 15/260 (5.77%)  20 0/49 (0.00%)  0 0/105 (0.00%)  0
Infections and infestations           
Bronchitis * 1  10/266 (3.76%)  10 10/271 (3.69%)  12 14/260 (5.38%)  18 3/49 (6.12%)  3 7/105 (6.67%)  9
Herpes zoster * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 4/49 (8.16%)  4 1/105 (0.95%)  1
Influenza * 1  13/266 (4.89%)  14 13/271 (4.80%)  18 15/260 (5.77%)  17 3/49 (6.12%)  4 7/105 (6.67%)  8
Nasopharyngitis * 1  17/266 (6.39%)  34 30/271 (11.07%)  40 20/260 (7.69%)  35 7/49 (14.29%)  7 15/105 (14.29%)  23
Upper respiratory tract infection * 1  11/266 (4.14%)  14 13/271 (4.80%)  15 18/260 (6.92%)  21 5/49 (10.20%)  5 10/105 (9.52%)  19
Urinary tract infection * 1  25/266 (9.40%)  37 16/271 (5.90%)  25 22/260 (8.46%)  38 4/49 (8.16%)  6 15/105 (14.29%)  25
Injury, poisoning and procedural complications           
Contusion * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 4/49 (8.16%)  4 5/105 (4.76%)  5
Fall * 1  28/266 (10.53%)  42 23/271 (8.49%)  32 27/260 (10.38%)  38 13/49 (26.53%)  20 17/105 (16.19%)  29
Skin laceration * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 0/49 (0.00%)  0 7/105 (6.67%)  8
Investigations           
Weight decreased * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 2/49 (4.08%)  2 6/105 (5.71%)  7
Musculoskeletal and connective tissue disorders           
Arthralgia * 1  21/266 (7.89%)  29 12/271 (4.43%)  14 16/260 (6.15%)  17 2/49 (4.08%)  2 8/105 (7.62%)  8
Back pain * 1  26/266 (9.77%)  33 16/271 (5.90%)  18 26/260 (10.00%)  32 2/49 (4.08%)  2 10/105 (9.52%)  10
Osteoporosis * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 3/49 (6.12%)  3 1/105 (0.95%)  1
Musculoskeletal pain * 1  16/266 (6.02%)  18 6/271 (2.21%)  7 5/260 (1.92%)  5 0/49 (0.00%)  0 0/105 (0.00%)  0
Nervous system disorders           
Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits * 1  31/266 (11.65%)  51 58/271 (21.40%)  92 36/260 (13.85%)  64 7/49 (14.29%)  12 17/105 (16.19%)  44
Amyloid related imaging abnormality-oedema/effusion * 1  2/266 (0.75%)  2 18/271 (6.64%)  20 34/260 (13.08%)  36 12/49 (24.49%)  21 29/105 (27.62%)  45
Dizziness * 1  21/266 (7.89%)  21 21/271 (7.75%)  27 26/260 (10.00%)  35 4/49 (8.16%)  5 14/105 (13.33%)  18
Headache * 1  36/266 (13.53%)  50 34/271 (12.55%)  47 25/260 (9.62%)  36 7/49 (14.29%)  11 12/105 (11.43%)  18
Psychiatric disorders           
Agitation * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 3/49 (6.12%)  4 8/105 (7.62%)  10
Anxiety * 1  18/266 (6.77%)  23 20/271 (7.38%)  20 16/260 (6.15%)  16 2/49 (4.08%)  2 7/105 (6.67%)  8
Confusional state * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 5/49 (10.20%)  5 8/105 (7.62%)  8
Irritability * 1  0/266 (0.00%)  0 0/271 (0.00%)  0 0/260 (0.00%)  0 1/49 (2.04%)  1 6/105 (5.71%)  9
Depression * 1  13/266 (4.89%)  14 23/271 (8.49%)  23 25/260 (9.62%)  25 0/49 (0.00%)  0 0/105 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Cough * 1  13/266 (4.89%)  14 11/271 (4.06%)  13 13/260 (5.00%)  13 5/49 (10.20%)  5 8/105 (7.62%)  12
Productive cough * 1