A Study of Semorinemab in Patients With Moderate Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT03828747
• Recruitment Status: Active, not recruiting
• First Posted: February 4, 2019
• Results First Posted: October 3, 2022
• Last Update Posted: October 3, 2022
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: January 29, 2019
• First Posted Date: February 4, 2019
• Results First Submitted Date: July 15, 2022
• Results First Posted Date: October 3, 2022
• Last Update Posted Date: October 3, 2022
• Actual Study Start Date: January 30, 2019
• Actual Primary Completion Date: July 20, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2022)

• Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) [ Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 ]
  The Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.
• Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) [ Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 ]
  The Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) is a scale used to quantify performance of activities of daily living (ADL). Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.

Original Primary Outcome Measures (submitted: January 31, 2019)

• Change from baseline to Week 49 in cognitive function as measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-item version (ADAS-Cog11) [ Time Frame: Baseline to Week 49 ]
  A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function.
• Change from baseline to Week 49 in functional capacities as measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) [ Time Frame: Baseline to Week 49 ]
  A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.

Current Secondary Outcome Measures (submitted: September 1, 2022)

• Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 ]
  The Clinical Dementia Rating-Sum of Boxes (CDR-SB) is a scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.
• Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE) [ Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 ]
  The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.
• Percentage of Participants With Adverse Events [ Time Frame: Baseline up to Clinical Cut Off Date (CCOD) of July 20, 2021 (approximately 2.5 years) ]
  An Adverse Event is any untoward medical occurrence in a subject 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.
• Serum Concentration of RO7105705 at Specified Timepoints [ Time Frame: Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2. ]
• Incidence of Anti-drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline [ Time Frame: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2. ]
• Relationship Between ADA Status and Percentage of Participants With Adverse Events [ Time Frame: Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2. ]
  Descriptive statistics will be used for assessment.
• Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer's Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) [ Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 ]
  Descriptive statistics will be used for assessment. A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function.
• Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL) [ Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 ]
  Descriptive statistics will be used for assessment. A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.
• Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 ]
  Descriptive statistics will be used for assessment. A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.
• Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE) [ Time Frame: Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2 ]
  Descriptive statistics will be used for assessment. The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.
• Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints [ Time Frame: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2. ]
  Descriptive statistics will be used for assessment.
• Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline [ Time Frame: Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2. ]
  Descriptive statistics will be used for assessment.

Original Secondary Outcome Measures (submitted: January 31, 2019)

• Change from baseline to Week 49 on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Baseline to Week 49 ]
  A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.
• Change from baseline to Week 49 on the Mini-Mental State Examination (MMSE) [ Time Frame: Baseline to Week 49 ]
  The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.
• Percentage of Participants with Adverse Events [ Time Frame: Up to approximately 51 months ]
• Serum concentration of MTAU9937A at specified timepoints [ Time Frame: Weeks 1, 3, 5, 9, 13, 25, 37, and 49, and at treatment discontinuation (up to week 48) ]
• Incidence of anti-drug antibodies (ADAs) during the study relative to the prevalence of ADAs at baseline [ Time Frame: Weeks 1, 13, 25, 37 and 49, and at treatment discontinuation (up to week 48) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Semorinemab in Patients With Moderate Alzheimer's Disease
• Official Title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937A in Patients With Moderate Alzheimer's Disease
• Brief Summary: This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in patients with moderate AD. The study consists of a screening period, a double-blind treatment period, an optional open-label extension (OLE) period, and a safety follow-up period. There may be up to two study cohorts.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease

Intervention

• Drug: Semorinemab
  Participants will receive semorinemab every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period.
  Other Names:

  • MTAU9937A
  • RO7105705
• Drug: Placebo
  Participants will receive placebo every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period.
• Drug: [18F]GTP1
  [18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.

Study Arms

• Experimental: Semorinemab
  Semorinemab will be administered intravenously in the double-blind treatment period, and semorinemab will be administered intravenously in the optional open-label extension period.
  Interventions:

  • Drug: Semorinemab
  • Drug: [18F]GTP1
• Placebo Comparator: Placebo
  Placebo will be administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.
  Interventions:

  • Drug: Placebo
  • Drug: [18F]GTP1

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 28, 2022): 272
• Original Estimated Enrollment (submitted: January 31, 2019): 260
• Estimated Study Completion Date: August 23, 2023
• Actual Primary Completion Date: July 20, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• National Institute on Aging/Alzheimer's Association core clinical criteria for probable AD dementia
• Evidence of the AD pathological process, by a positive amyloid assessment either on CSF Aβ1-42 as measured on Elecsys β-Amyloid(1-42) Test System OR amyloid PET scan
• AD dementia of moderate severity, as defined by a screening MMSE score of 16-21 points, inclusive, and a CDR-GS of 1 or 2
• Availability of a person with sufficient contact with the participant to be able to provide accurate information on the participant's cognitive, behavioral and functional ability

Exclusion Criteria:

• Pregnant or breastfeeding
• Inability to tolerate MRI procedures or contraindication to MRI
• Contraindication to PET imaging
• Residence in a skilled nursing facility
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study, or bias the assessment of the clinical or mental status of the participant to a significant degree
• Any evidence of a condition other than AD that may affect cognition
• Substance abuse within the past 2 years
• Use of any experimental therapy within 90 days or 5 half-lives prior to screening, whichever is greater, or any passive immunotherapy against tau
• Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was at least 1 year prior to screening or any active immunotherapy (vaccine) that is under evaluation to prevent or postpone cognitive decline
• Any other biologic therapy or previous treatment with medications specifically intended to treat Parkinsonian symptoms or any other non-AD neurodegenerative disorder within 1 year of screening
• Systemic immunosuppressive therapy within 12 months of screening through the entire study period
• Typical antipsychotic or neuroleptic medication within 6 months of screening
• Daily treatment with any of the following classes of medication (except for intermittent short-term use): opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally-acting antihistamine or anticholinergic activity
• Stimulant medications, unless the dose has been stable within the 6 months prior to screening and is expected to be stable throughout the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Poland, Spain, United States

Administrative Information

• NCT Number: NCT03828747
• Other Study ID Numbers: GN40040
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)

• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Genentech, Inc.
• Verification Date: September 2022