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Phase 3 Study of Dexpramipexole in ALS (EMPOWER)

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ClinicalTrials.gov Identifier: NCT01281189
Recruitment Status : Completed
First Posted : January 21, 2011
Results First Posted : June 7, 2021
Last Update Posted : June 7, 2021
Sponsor:
Information provided by (Responsible Party):
Knopp Biosciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Amyotrophic Lateral Sclerosis
Interventions Drug: Dexpramipexole
Drug: Placebo
Enrollment 942
Recruitment Details There were 942 participants (468 received placebo and 474 received dexpramipexole) recruited from 81 investigational sites in 11 countries worldwide. One additional participant was randomized in error and was not dosed. This subject was assigned to the placebo arm, but was removed from the intent-to-treat population as a result of the unintentional randomization performed in error by the site.
Pre-assignment Details  
Arm/Group Title Placebo Dexpramipexole
Hide Arm/Group Description Matching Placebo: Oral tablet twice daily. Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day
Period Title: Overall Study
Started 468 474
Completed 321 331
Not Completed 147 143
Reason Not Completed
Adverse Event             7             9
Lost to Follow-up             6             4
Withdrawal by Subject             21             24
Physician Decision             2             3
Death             103             91
Other             8             12
Arm/Group Title Placebo Dexpramipexole Total
Hide Arm/Group Description Matching Placebo: Oral tablet twice daily. Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day Total of all reporting groups
Overall Number of Baseline Participants 468 474 942
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population is defined as subjects who were randomized and received at least 1 dose of study treatment.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Age (yrs) Number Analyzed 468 participants 474 participants 942 participants
<50
114
  24.4%
114
  24.1%
228
  24.2%
50-65
233
  49.8%
244
  51.5%
477
  50.6%
>65
121
  25.9%
116
  24.5%
237
  25.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 468 participants 474 participants 942 participants
Female
170
  36.3%
167
  35.2%
337
  35.8%
Male
298
  63.7%
307
  64.8%
605
  64.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 468 participants 474 participants 942 participants
Asian
7
   1.5%
4
   0.8%
11
   1.2%
Black or African American
10
   2.1%
3
   0.6%
13
   1.4%
White
439
  93.8%
450
  94.9%
889
  94.4%
Not reported
7
   1.5%
9
   1.9%
16
   1.7%
Other
5
   1.1%
8
   1.7%
13
   1.4%
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 465 participants 471 participants 936 participants
77.76  (16.008) 77.21  (15.027) 77.48  (15.516)
[1]
Measure Analysis Population Description: Not all subject in the safety population had valid weights collected at Baseline
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 468 participants 474 participants 942 participants
172.0  (10.22) 172.0  (9.30) 172.0  (9.77)
Body mass index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 465 participants 471 participants 936 participants
26.15  (4.330) 26.00  (4.239) 26.08  (4.283)
[1]
Measure Analysis Population Description: Not all subject in the safety population had valid weights collected at Baseline, therefore BMI could not be calculated.
ALS family history  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 468 participants 474 participants 942 participants
Yes
26
   5.6%
33
   7.0%
59
   6.3%
No
442
  94.4%
440
  92.8%
882
  93.6%
Missing
0
   0.0%
1
   0.2%
1
   0.1%
Time since ALS symptom onset  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 468 participants 474 participants 942 participants
15.53  (5.411) 14.92  (5.251) 15.22  (5.337)
Site of onset  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 468 participants 474 participants 942 participants
Bulbar
112
  23.9%
107
  22.6%
219
  23.2%
Other
356
  76.1%
367
  77.4%
723
  76.8%
Time since ALS diagnosis  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 468 participants 474 participants 942 participants
7.62  (5.015) 7.22  (4.718) 7.42  (4.869)
El Escorial Criteria for ALS  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 468 participants 474 participants 942 participants
Possible
44
   9.4%
44
   9.3%
88
   9.3%
Probable laboratory supported
94
  20.1%
98
  20.7%
192
  20.4%
Probable
174
  37.2%
185
  39.0%
359
  38.1%
Definite
156
  33.3%
147
  31.0%
303
  32.2%
Concomitant use of riluzole  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 468 participants 474 participants 942 participants
Yes
349
  74.6%
359
  75.7%
708
  75.2%
No
119
  25.4%
115
  24.3%
234
  24.8%
Baseline ALSFRS-R total scores   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 468 participants 474 participants 942 participants
37.9  (5.65) 38.4  (5.24) 38.2  (5.45)
[1]
Measure Description: Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). This validated scale stratifies severity of amyotrophic lateral sclerosis (ALS). The ALSFRS-R consists of 12 items answered across 4 functional domains (bulbar, gross motor, fine motor and respiratory) in which each item is scored between 4 and 0, for a maximum score of 48. A decline in ALSFRS-R indicates a loss of physical function.
Baseline predicted upright slow vital capacity (%)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 468 participants 474 participants 942 participants
<65%
27
   5.8%
28
   5.9%
55
   5.8%
65-75%
84
  17.9%
79
  16.7%
163
  17.3%
>75%
357
  76.3%
367
  77.4%
724
  76.9%
[1]
Measure Description: slow vital capacity
Baseline predicted upright slow vital capacity (%)   [1] 
Mean (Standard Deviation)
Unit of measure:  %
Number Analyzed 468 participants 474 participants 942 participants
89.1  (17.71) 89.0  (17.57) 89.1  (17.63)
[1]
Measure Description: slow vital capacity
1.Primary Outcome
Title Composite Assessment of Function and Survival (CAFS) at 12 Months
Hide Description The Composite Assessment of Function and Survival (CAFS) is a between-group comparison of a single ranked clinical outcome based on (1) the change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) score and (2) time to death. Each subject is ranked according to time-to-death (earlier deaths ranked lower than later deaths). Subjects who survive are ranked more favorably than subjects who died. Among the survivors, subjects are ranked according to change in ALSFRS-R (greater worsening of ALSFRS-R is ranked lower than less worsening or an improvement in ALSFRS-R). The ranked scores range from 001 to 941 (the number of subjects in the Efficacy Population) with larger rank score numbers associated with a better outcome. The ranks were analyzed using an ANCOVA model, which includes treatment as a fixed effect and adjusts for baseline ALSFRS-R score, duration of symptoms, site of onset, and use of riluzole. The least square mean rank score is presented for each treatment group.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population is defined as subjects who were randomized and received at least 1 dose of study treatment and who either had at least 1 available post-dosing efficacy evaluation (ALSFRS-R) or died during the study period. Subjects were analyzed in the treatment group to which they are randomized.
Arm/Group Title Placebo Dexpramipexole
Hide Arm/Group Description:
Matching Placebo: Oral tablet twice daily.
Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day
Overall Number of Participants Analyzed 468 473
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
438.84
(412.807 to 464.878)
441.76
(415.426 to 468.084)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dexpramipexole
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8568
Comments [Not Specified]
Method ANCOVA
Comments Includes treatment as a fixed effect and adjusts for baseline ALSFRS-R total score, duration from sx onset, site of onset, and use of riluzole.
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 2.91
Confidence Interval (2-Sided) 95%
-28.751 to 34.576
Estimation Comments [Not Specified]
2.Primary Outcome
Title Death up to 12 Months (CAFs Individual Component)
Hide Description The longest duration of follow-up for this time to the death analysis was 12 months. In the study, subjects were followed for 12-18 months.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population is defined as subjects who were randomized and received at least 1 dose of study treatment and who either had at least 1 available post-dosing efficacy evaluation (ALSFRS-R) or died during the study period. Subjects were analyzed in the treatment group to which they are randomized.
Arm/Group Title Placebo Dexpramipexole
Hide Arm/Group Description:
Matching Placebo: Oral tablet twice daily.
Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day
Overall Number of Participants Analyzed 468 473
Measure Type: Number
Unit of Measure: percentage of participants
17.2 16.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dexpramipexole
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8375
Comments [Not Specified]
Method Cox Proportional Hazards model
Comments Adjusted for baseline ALSFRS-R total score, duration from symptom onset to the first dose of study treatment, site of onset, and use of riluzole.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.750 to 1.427
Estimation Comments [Not Specified]
Other Statistical Analysis Hazard Ratio (HR) (Dex/PBO)
3.Primary Outcome
Title Change From Baseline in ALSFRS-R at 12 Months (CAFs Individual Component)
Hide Description The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48, with higher scores representing better function.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population is defined as subjects who were randomized and received at least 1 dose of study treatment and who either had at least 1 available post-dosing efficacy evaluation (ALSFRS-R) or died during the study period. Subjects will be analyzed in the treatment group to which they are randomized.
Arm/Group Title Placebo Dexpramipexole
Hide Arm/Group Description:
Matching Placebo: Oral tablet twice daily.
Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day
Overall Number of Participants Analyzed 468 473
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-13.415
(-14.275 to -12.555)
-13.339
(-14.199 to -12.480)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dexpramipexole
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9019
Comments [Not Specified]
Method mixed-effects repeated-measures model
Comments Mixed-effects repeated-measures model with treatment, visit, treatment-by visit interaction, baseline ALSFRS-R score, baseline-by-visit interaction
Method of Estimation Estimation Parameter LS Mean Difference (Net)
Estimated Value 0.076
Confidence Interval (2-Sided) 95%
-1.128 to 1.280
Estimation Comments The mixed-effects repeated-measures model also adjusted for the following covariates: duration from symptom onset, site of onset, and use of riluzole.
4.Secondary Outcome
Title Death or Respiratory Insufficiency (DRI) up to Month 18
Hide Description Time to Death or Respiratory Insufficiency (DRI) is defined as receipt of a tracheostomy or the use of non-invasive ventilation (NIV) for ≥22 hours per day for at least 10 consecutive days. If NIV is used to meet the criteria for respiratory insufficiency, no measured slow vital capacity (SVC) at any subsequent assessment may be >50%. Time to DRI is calculated from the date of the first dose to the first date of one of the following events: death, tracheostomy, or the 10th day of consecutive NIV with no measured SVC >50% at any subsequent assessment.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population is defined as subjects who were randomized and received at least 1 dose of study treatment and who either had at least 1 available post-dosing efficacy evaluation (ALSFRS-R) or died during the study period. Subjects were analyzed in the treatment group to which they are randomized.
Arm/Group Title Placebo Dexpramipexole
Hide Arm/Group Description:
Matching Placebo: Oral tablet twice daily.
Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day
Overall Number of Participants Analyzed 468 474
Measure Type: Number
Unit of Measure: percentage of participants
27.2 22.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dexpramipexole
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7715
Comments [Not Specified]
Method Cox Proportional Hazards model
Comments Adjusted for baseline ALSFRS-R total score, duration from symptom onset to the first dose of study treatment, site of onset, and use of riluzole
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.801 to 1.348
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Death up to 18 Months
Hide Description Estimated time to death up to 18 months. This includes deaths reported greater than 30 days following discontinuation from the study (the time period for reporting all-cause mortality), regardless of subject disposition, up to 18 months from first dose.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects who were randomized, received at least 1 dose of study treatment, had at least 1 available post-dosing efficacy evaluation (ALSFRS-R) or died during the study period. Subjects were analyzed in the treatment group to which they are randomized. An attempt was made to collect living status for each subject 18 months after randomization, regardless of the subject's disposition in the study (active or discontinued) or primary reasons for discontinuation.
Arm/Group Title Placebo Dexpramipexole
Hide Arm/Group Description:
Matching Placebo: Oral tablet twice daily.
Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day
Overall Number of Participants Analyzed 468 474
Measure Type: Number
Unit of Measure: percentage of participants
23.1 20.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dexpramipexole
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9033
Comments [Not Specified]
Method Cox Proportional Hazards model
Comments adjusted for baseline ALSFRS-R total score, duration from symptom onset to the first dose of study treatment, site of onset, and use of riluzole
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.745 to 1.298
Estimation Comments [Not Specified]
6.Secondary Outcome
Title ≤50% Predicted Upright Slow Vital Capacity (SVC) or Died up to 18 Months
Hide Description The date of reaching ≤50% of predicted upright slow vital capacity (SVC) is defined as the date of the first visit at which a predicted upright SVC is ≤50% and continues to remain ≤50% at the subsequent visit except for the last available observation. The time to reach ≤50% of predicted upright SVC is defined as the duration between the date of reaching ≤50% of predicted upright SVC and the date of the first dose of study medication. If the subject is alive and does not reach ≤50% of predicted upright SVC, the time to reach ≤50% of predicted upright SVC will be censored and equal to the number of days from the first dose of study medication until the visit date when the subject's last available SVC assessment is performed. The earliest time (Reaching ≤50% Predicted Upright SVC or death) is used in analysis.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population is defined as subjects who were randomized and received at least 1 dose of study treatment.
Arm/Group Title Placebo Dexpramipexole
Hide Arm/Group Description:
Matching Placebo: Oral tablet twice daily.
Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day
Overall Number of Participants Analyzed 468 474
Measure Type: Number
Unit of Measure: percentage of participants
41.9 36.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dexpramipexole
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7720
Comments [Not Specified]
Method Cox Proportional Hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.789 to 1.192
Estimation Comments Hazard ratio (Dex/PBO)
Time Frame 18 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Dexpramipexole
Hide Arm/Group Description Matching Placebo: Oral tablet twice daily. Dexpramipexole: Oral tablet 150 mg twice daily. 300 mg/day
All-Cause Mortality
Placebo Dexpramipexole
Affected / at Risk (%) Affected / at Risk (%)
Total   108/468 (23.08%)   97/474 (20.46%) 
Hide Serious Adverse Events
Placebo Dexpramipexole
Affected / at Risk (%) Affected / at Risk (%)
Total   233/468 (49.79%)   225/474 (47.47%) 
Blood and lymphatic system disorders     
NEUTROPENIA * 1  1/468 (0.21%)  9/474 (1.90%) 
ANAEMIA * 1  0/468 (0.00%)  1/474 (0.21%) 
FEBRILE NEUTROPENIA * 1  0/468 (0.00%)  1/474 (0.21%) 
COAGULOPATHY * 1  1/468 (0.21%)  0/474 (0.00%) 
Cardiac disorders     
CARDIO-RESPIRATORY ARREST * 1  3/468 (0.64%)  5/474 (1.05%) 
MYOCARDIAL INFARCTION * 1  1/468 (0.21%)  4/474 (0.84%) 
ACUTE MYOCARDIAL INFARCTION * 1  2/468 (0.43%)  3/474 (0.63%) 
ARRHYTHMIA * 1  0/468 (0.00%)  2/474 (0.42%) 
CARDIAC ARREST * 1  0/468 (0.00%)  2/474 (0.42%) 
ATRIAL FIBRILLATION * 1  3/468 (0.64%)  1/474 (0.21%) 
CARDIOGENIC SHOCK * 1  0/468 (0.00%)  1/474 (0.21%) 
CARDIOVASCULAR DISORDER * 1  0/468 (0.00%)  1/474 (0.21%) 
SINUS TACHYCARDIA * 1  1/468 (0.21%)  1/474 (0.21%) 
SUPRAVENTRICULAR EXTRASYSTOLES * 1  0/468 (0.00%)  1/474 (0.21%) 
SUPRAVENTRICULAR TACHYCARDIA * 1  2/468 (0.43%)  1/474 (0.21%) 
VENTRICULAR ARRHYTHMIA * 1  0/468 (0.00%)  1/474 (0.21%) 
CARDIOPULMONARY FAILURE * 1  2/468 (0.43%)  0/474 (0.00%) 
CORONARY ARTERY DISEASE * 1  1/468 (0.21%)  0/474 (0.00%) 
DIASTOLIC DYSFUNCTION * 1  1/468 (0.21%)  0/474 (0.00%) 
STRESS CARDIOMYOPATHY * 1  1/468 (0.21%)  0/474 (0.00%) 
TACHYCARDIA * 1  1/468 (0.21%)  0/474 (0.00%) 
Eye disorders     
CATARACT * 1  1/468 (0.21%)  0/474 (0.00%) 
Gastrointestinal disorders     
DYSPHAGIA * 1  69/468 (14.74%)  62/474 (13.08%) 
ABDOMINAL PAIN * 1  2/468 (0.43%)  2/474 (0.42%) 
APHAGIA * 1  1/468 (0.21%)  2/474 (0.42%) 
CONSTIPATION * 1  4/468 (0.85%)  2/474 (0.42%) 
FAECALOMA * 1  0/468 (0.00%)  2/474 (0.42%) 
ABDOMINAL DISTENSION * 1  0/468 (0.00%)  1/474 (0.21%) 
COLITIS * 1  0/468 (0.00%)  1/474 (0.21%) 
FLATULENCE * 1  0/468 (0.00%)  1/474 (0.21%) 
INTESTINAL OBSTRUCTION * 1  1/468 (0.21%)  1/474 (0.21%) 
STOMATITIS * 1  0/468 (0.00%)  1/474 (0.21%) 
GASTRITIS * 1  1/468 (0.21%)  0/474 (0.00%) 
ILEUS * 1  2/468 (0.43%)  0/474 (0.00%) 
OESOPHAGEAL STENOSIS * 1  1/468 (0.21%)  0/474 (0.00%) 
OESOPHAGITIS * 1  1/468 (0.21%)  0/474 (0.00%) 
RECTAL HAEMORRHAGE * 1  2/468 (0.43%)  0/474 (0.00%) 
General disorders     
EUTHANASIA * 1  1/468 (0.21%)  2/474 (0.42%) 
NON-CARDIAC CHEST PAIN * 1  0/468 (0.00%)  2/474 (0.42%) 
SUDDEN DEATH * 1  0/468 (0.00%)  2/474 (0.42%) 
ADVERSE DRUG REACTION * 1  0/468 (0.00%)  1/474 (0.21%) 
ASTHENIA * 1  0/468 (0.00%)  1/474 (0.21%) 
CATHETER SITE HAEMORRHAGE * 1  0/468 (0.00%)  1/474 (0.21%) 
CHEST PAIN * 1  0/468 (0.00%)  1/474 (0.21%) 
COMPLICATION OF DEVICE INSERTION * 1  0/468 (0.00%)  1/474 (0.21%) 
DEATH * 1  1/468 (0.21%)  1/474 (0.21%) 
DEVICE MALFUNCTION * 1  0/468 (0.00%)  1/474 (0.21%) 
MEDICAL DEVICE COMPLICATION * 1  0/468 (0.00%)  1/474 (0.21%) 
PYREXIA * 1  1/468 (0.21%)  1/474 (0.21%) 
ULCER HAEMORRHAGE * 1  0/468 (0.00%)  1/474 (0.21%) 
DEVICE LEAKAGE * 1  1/468 (0.21%)  0/474 (0.00%) 
DEVICE OCCLUSION * 1  1/468 (0.21%)  0/474 (0.00%) 
GENERAL PHYSICAL HEALTH DETERIORATION * 1  1/468 (0.21%)  0/474 (0.00%) 
OEDEMA PERIPHERAL * 1  1/468 (0.21%)  0/474 (0.00%) 
Hepatobiliary disorders     
CHOLELITHIASIS * 1  0/468 (0.00%)  1/474 (0.21%) 
CHOLECYSTITIS * 1  1/468 (0.21%)  0/474 (0.00%) 
Immune system disorders     
HYPERSENSITIVITY * 1  0/468 (0.00%)  1/474 (0.21%) 
Infections and infestations     
PNEUMONIA * 1  19/468 (4.06%)  14/474 (2.95%) 
LOWER RESPIRATORY TRACT INFECTION * 1  6/468 (1.28%)  3/474 (0.63%) 
URINARY TRACT INFECTION * 1  3/468 (0.64%)  3/474 (0.63%) 
BRONCHITIS * 1  6/468 (1.28%)  2/474 (0.42%) 
CELLULITIS * 1  0/468 (0.00%)  2/474 (0.42%) 
LUNG INFECTION * 1  0/468 (0.00%)  2/474 (0.42%) 
UPPER RESPIRATORY TRACT INFECTION * 1  0/468 (0.00%)  2/474 (0.42%) 
CATHETER SITE INFECTION * 1  1/468 (0.21%)  1/474 (0.21%) 
CLOSTRIDIUM DIFFICILE COLITIS * 1  1/468 (0.21%)  1/474 (0.21%) 
CYSTITIS ESCHERICHIA * 1  0/468 (0.00%)  1/474 (0.21%) 
GASTROENTERITIS VIRAL * 1  0/468 (0.00%)  1/474 (0.21%) 
NEUTROPENIC INFECTION * 1  0/468 (0.00%)  1/474 (0.21%) 
PILONIDAL CYST * 1  0/468 (0.00%)  1/474 (0.21%) 
PSEUDOMONAS BRONCHITIS * 1  0/468 (0.00%)  1/474 (0.21%) 
RHINITIS * 1  0/468 (0.00%)  1/474 (0.21%) 
RHINOVIRUS INFECTION * 1  1/468 (0.21%)  1/474 (0.21%) 
STAPHYLOCOCCAL INFECTION * 1  0/468 (0.00%)  1/474 (0.21%) 
VIRAL INFECTION * 1  0/468 (0.00%)  1/474 (0.21%) 
VIRAL UPPER RESPIRATORY TRACT INFECTION * 1  0/468 (0.00%)  1/474 (0.21%) 
BRONCHOPNEUMONIA * 1  1/468 (0.21%)  0/474 (0.00%) 
DEVICE RELATED INFECTION * 1  1/468 (0.21%)  0/474 (0.00%) 
GAS GANGRENE * 1  1/468 (0.21%)  0/474 (0.00%) 
GASTROENTERITIS * 1  1/468 (0.21%)  0/474 (0.00%) 
PNEUMONIA KLEBSIELLA * 1  2/468 (0.43%)  0/474 (0.00%) 
PYELONEPHRITIS * 1  1/468 (0.21%)  0/474 (0.00%) 
RESPIRATORY SYNCYTIAL VIRUS BRONCHITIS * 1  1/468 (0.21%)  0/474 (0.00%) 
RESPIRATORY TRACT INFECTION * 1  2/468 (0.43%)  0/474 (0.00%) 
SEPSIS * 1  1/468 (0.21%)  0/474 (0.00%) 
SERRATIA INFECTION * 1  1/468 (0.21%)  0/474 (0.00%) 
SINUSITIS * 1  1/468 (0.21%)  0/474 (0.00%) 
Injury, poisoning and procedural complications     
FALL * 1  11/468 (2.35%)  13/474 (2.74%) 
FACIAL BONES FRACTURE * 1  1/468 (0.21%)  2/474 (0.42%) 
LACERATION * 1  1/468 (0.21%)  2/474 (0.42%) 
SUBDURAL HAEMATOMA * 1  3/468 (0.64%)  2/474 (0.42%) 
ANKLE FRACTURE * 1  0/468 (0.00%)  1/474 (0.21%) 
CONCUSSION * 1  2/468 (0.43%)  1/474 (0.21%) 
CRANIOCEREBRAL INJURY * 1  1/468 (0.21%)  1/474 (0.21%) 
FEMUR FRACTURE * 1  1/468 (0.21%)  1/474 (0.21%) 
FOREIGN BODY * 1  0/468 (0.00%)  1/474 (0.21%) 
GASTROINTESTINAL STOMA COMPLICATION * 1  0/468 (0.00%)  1/474 (0.21%) 
HAND FRACTURE * 1  0/468 (0.00%)  1/474 (0.21%) 
HIP FRACTURE * 1  0/468 (0.00%)  1/474 (0.21%) 
HUMERUS FRACTURE * 1  0/468 (0.00%)  1/474 (0.21%) 
POST PROCEDURAL HAEMORRHAGE * 1  0/468 (0.00%)  1/474 (0.21%) 
RADIUS FRACTURE * 1  0/468 (0.00%)  1/474 (0.21%) 
SPLENIC HAEMATOMA * 1  0/468 (0.00%)  1/474 (0.21%) 
CLAVICLE FRACTURE * 1  1/468 (0.21%)  0/474 (0.00%) 
CONTUSION * 1  1/468 (0.21%)  0/474 (0.00%) 
HEAD INJURY * 1  1/468 (0.21%)  0/474 (0.00%) 
INTENTIONAL OVERDOSE * 1  1/468 (0.21%)  0/474 (0.00%) 
POST PROCEDURAL COMPLICATION * 1  1/468 (0.21%)  0/474 (0.00%) 
SKELETAL INJURY * 1  1/468 (0.21%)  0/474 (0.00%) 
SKULL FRACTURED BASE * 1  2/468 (0.43%)  0/474 (0.00%) 
TRAUMATIC INTRACRANIAL HAEMORRHAGE * 1  1/468 (0.21%)  0/474 (0.00%) 
TRENCH FOOT * 1  1/468 (0.21%)  0/474 (0.00%) 
Investigations     
VITAL CAPACITY DECREASED * 1  3/468 (0.64%)  3/474 (0.63%) 
WEIGHT DECREASED * 1  1/468 (0.21%)  2/474 (0.42%) 
INVESTIGATION * 1  0/468 (0.00%)  1/474 (0.21%) 
LIVER FUNCTION TEST ABNORMAL * 1  0/468 (0.00%)  1/474 (0.21%) 
DIAGNOSTIC PROCEDURE * 1  1/468 (0.21%)  0/474 (0.00%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED * 1  1/468 (0.21%)  0/474 (0.00%) 
OXYGEN SATURATION DECREASED * 1  2/468 (0.43%)  0/474 (0.00%) 
TOTAL LUNG CAPACITY DECREASED * 1  1/468 (0.21%)  0/474 (0.00%) 
Metabolism and nutrition disorders     
DEHYDRATION * 1  1/468 (0.21%)  2/474 (0.42%) 
ELECTROLYTE IMBALANCE * 1  0/468 (0.00%)  2/474 (0.42%) 
HYPOKALAEMIA * 1  1/468 (0.21%)  2/474 (0.42%) 
HYPONATRAEMIA * 1  0/468 (0.00%)  2/474 (0.42%) 
DECREASED APPETITE * 1  0/468 (0.00%)  1/474 (0.21%) 
FAILURE TO THRIVE * 1  0/468 (0.00%)  1/474 (0.21%) 
MALNUTRITION * 1  1/468 (0.21%)  1/474 (0.21%) 
FLUID RETENTION * 1  1/468 (0.21%)  0/474 (0.00%) 
HYPOCALCAEMIA * 1  1/468 (0.21%)  0/474 (0.00%) 
Musculoskeletal and connective tissue disorders     
MUSCULOSKELETAL CHEST PAIN * 1  1/468 (0.21%)  2/474 (0.42%) 
INTERVERTEBRAL DISC DEGENERATION * 1  0/468 (0.00%)  1/474 (0.21%) 
MOBILITY DECREASED * 1  0/468 (0.00%)  1/474 (0.21%) 
OSTEOARTHRITIS * 1  1/468 (0.21%)  1/474 (0.21%) 
POLYMYALGIA RHEUMATICA * 1  0/468 (0.00%)  1/474 (0.21%) 
INCLUSION BODY MYOSITIS * 1  1/468 (0.21%)  0/474 (0.00%) 
INTERVERTEBRAL DISC PROTRUSION * 1  1/468 (0.21%)  0/474 (0.00%) 
LUMBAR SPINAL STENOSIS * 1  1/468 (0.21%)  0/474 (0.00%) 
MUSCLE SPASMS * 1  1/468 (0.21%)  0/474 (0.00%) 
NOSE DEFORMITY * 1  1/468 (0.21%)  0/474 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
MALIGNANT MELANOMA * 1  0/468 (0.00%)  1/474 (0.21%) 
NEOPLASM MALIGNANT * 1  0/468 (0.00%)  1/474 (0.21%) 
CHRONIC LYMPHOCYTIC LEUKAEMIA * 1  1/468 (0.21%)  0/474 (0.00%) 
METASTATIC BRONCHIAL CARCINOMA * 1  1/468 (0.21%)  0/474 (0.00%) 
Nervous system disorders     
AMYOTROPHIC LATERAL SCLEROSIS * 1  16/468 (3.42%)  16/474 (3.38%) 
MOTOR NEURONE DISEASE * 1  7/468 (1.50%)  3/474 (0.63%) 
MIGRAINE * 1  0/468 (0.00%)  1/474 (0.21%) 
MUSCLE SPASTICITY * 1  0/468 (0.00%)  1/474 (0.21%) 
SOMNOLENCE * 1  0/468 (0.00%)  1/474 (0.21%) 
SYNCOPE * 1  2/468 (0.43%)  1/474 (0.21%) 
TRANSIENT ISCHAEMIC ATTACK * 1  0/468 (0.00%)  1/474 (0.21%) 
BULBAR PALSY * 1  1/468 (0.21%)  0/474 (0.00%) 
CEREBELLAR INFARCTION * 1  1/468 (0.21%)  0/474 (0.00%) 
CEREBROVASCULAR ACCIDENT * 1  1/468 (0.21%)  0/474 (0.00%) 
VERTEBRAL ARTERY DISSECTION * 1  1/468 (0.21%)  0/474 (0.00%) 
Psychiatric disorders     
SUICIDAL IDEATION * 1  1/468 (0.21%)  1/474 (0.21%) 
ALCOHOLISM * 1  1/468 (0.21%)  0/474 (0.00%) 
ANXIETY * 1  1/468 (0.21%)  0/474 (0.00%) 
COMPLETED SUICIDE * 1  1/468 (0.21%)  0/474 (0.00%) 
DEPRESSION * 1  1/468 (0.21%)  0/474 (0.00%) 
DEPRESSION SUICIDAL * 1  1/468 (0.21%)  0/474 (0.00%) 
PANIC ATTACK * 1  1/468 (0.21%)  0/474 (0.00%) 
Renal and urinary disorders     
RENAL FAILURE ACUTE * 1  0/468 (0.00%)  3/474 (0.63%) 
URINARY RETENTION * 1  1/468 (0.21%)  2/474 (0.42%) 
HAEMATURIA * 1  0/468 (0.00%)  1/474 (0.21%) 
NEPHROLITHIASIS * 1  0/468 (0.00%)  1/474 (0.21%) 
RENAL FAILURE * 1  0/468 (0.00%)  1/474 (0.21%) 
URETERIC STENOSIS * 1  1/468 (0.21%)  0/474 (0.00%) 
Reproductive system and breast disorders     
UTERINE POLYP * 1  0/468 (0.00%)  1/474 (0.21%) 
BREAST HAEMATOMA * 1  1/468 (0.21%)  0/474 (0.00%) 
VAGINAL HAEMORRHAGE * 1  1/468 (0.21%)  0/474 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
RESPIRATORY FAILURE * 1  75/468 (16.03%)  69/474 (14.56%) 
PNEUMONIA ASPIRATION * 1  13/468 (2.78%)  12/474 (2.53%) 
PULMONARY EMBOLISM * 1  9/468 (1.92%)  12/474 (2.53%) 
DYSPNOEA * 1  10/468 (2.14%)  6/474 (1.27%) 
ACUTE RESPIRATORY FAILURE * 1  5/468 (1.07%)  4/474 (0.84%) 
RESPIRATORY DISORDER * 1  6/468 (1.28%)  4/474 (0.84%) 
RESPIRATORY DISTRESS * 1  6/468 (1.28%)  3/474 (0.63%) 
RESPIRATORY ARREST * 1  6/468 (1.28%)  2/474 (0.42%) 
CHRONIC RESPIRATORY FAILURE * 1  0/468 (0.00%)  1/474 (0.21%) 
COUGH DECREASED * 1  0/468 (0.00%)  1/474 (0.21%) 
HYPERCAPNIA * 1  4/468 (0.85%)  1/474 (0.21%) 
HYPOVENTILATION * 1  0/468 (0.00%)  1/474 (0.21%) 
HYPOXIA * 1  1/468 (0.21%)  1/474 (0.21%) 
INCREASED BRONCHIAL SECRETION * 1  1/468 (0.21%)  1/474 (0.21%) 
LUNG DISORDER * 1  3/468 (0.64%)  1/474 (0.21%) 
ORTHOPNOEA * 1  0/468 (0.00%)  1/474 (0.21%) 
PULMONARY OEDEMA * 1  0/468 (0.00%)  1/474 (0.21%) 
RESPIRATORY MUSCLE WEAKNESS * 1  0/468 (0.00%)  1/474 (0.21%) 
RESPIRATORY TRACT CONGESTION * 1  0/468 (0.00%)  1/474 (0.21%) 
SLEEP APNOEA SYNDROME * 1  0/468 (0.00%)  1/474 (0.21%) 
UPPER AIRWAY OBSTRUCTION * 1  0/468 (0.00%)  1/474 (0.21%) 
ATELECTASIS * 1  2/468 (0.43%)  0/474 (0.00%) 
EPISTAXIS * 1  1/468 (0.21%)  0/474 (0.00%) 
INCREASED VISCOSITY OF BRONCHIAL SECRETION * 1  1/468 (0.21%)  0/474 (0.00%) 
LARYNGOSPASM * 1  1/468 (0.21%)  0/474 (0.00%) 
PLEURAL EFFUSION * 1  1/468 (0.21%)  0/474 (0.00%) 
RESPIRATORY ACIDOSIS * 1  1/468 (0.21%)  0/474 (0.00%) 
STRIDOR * 1  1/468 (0.21%)  0/474 (0.00%) 
VOCAL CORD DISORDER * 1  1/468 (0.21%)  0/474 (0.00%) 
Skin and subcutaneous tissue disorders     
SKIN ULCER * 1  0/468 (0.00%)  1/474 (0.21%) 
Social circumstances     
RESPITE CARE * 1  1/468 (0.21%)  0/474 (0.00%) 
SOCIAL STAY HOSPITALISATION * 1  1/468 (0.21%)  0/474 (0.00%) 
Surgical and medical procedures     
SUPPORTIVE CARE * 1  1/468 (0.21%)  0/474 (0.00%) 
Vascular disorders     
DEEP VEIN THROMBOSIS * 1  8/468 (1.71%)  8/474 (1.69%) 
ARTERIAL THROMBOSIS LIMB * 1  0/468 (0.00%)  1/474 (0.21%) 
HAEMATOMA * 1  0/468 (0.00%)  1/474 (0.21%) 
HYPERTENSION * 1  1/468 (0.21%)  0/474 (0.00%) 
ORTHOSTATIC HYPOTENSION * 1  1/468 (0.21%)  0/474 (0.00%) 
THROMBOSIS * 1  1/468 (0.21%)  0/474 (0.00%) 
1
Term from vocabulary, MedDRA 15.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Dexpramipexole
Affected / at Risk (%) Affected / at Risk (%)
Total   447/468 (95.51%)   459/474 (96.84%) 
Blood and lymphatic system disorders     
NEUTROPENIA * 1  8/468 (1.71%)  37/474 (7.81%) 
Gastrointestinal disorders     
CONSTIPATION * 1  109/468 (23.29%)  129/474 (27.22%) 
NAUSEA * 1  65/468 (13.89%)  106/474 (22.36%) 
DYSPHAGIA * 1  95/468 (20.30%)  88/474 (18.57%) 
DIARRHOEA * 1  55/468 (11.75%)  44/474 (9.28%) 
DRY MOUTH * 1  20/468 (4.27%)  41/474 (8.65%) 
SALIVARY HYPERSECRETION * 1  34/468 (7.26%)  29/474 (6.12%) 
General disorders     
OEDEMA PERIPHERAL * 1  72/468 (15.38%)  61/474 (12.87%) 
FATIGUE * 1  60/468 (12.82%)  57/474 (12.03%) 
ASTHENIA * 1  10/468 (2.14%)  23/474 (4.85%) 
PYREXIA * 1  21/468 (4.49%)  22/474 (4.64%) 
Infections and infestations     
NASOPHARYNGITIS * 1  76/468 (16.24%)  69/474 (14.56%) 
URINARY TRACT INFECTION * 1  56/468 (11.97%)  56/474 (11.81%) 
UPPER RESPIRATORY TRACT INFECTION * 1  17/468 (3.63%)  30/474 (6.33%) 
PNEUMONIA * 1  32/468 (6.84%)  24/474 (5.06%) 
BRONCHITIS * 1  28/468 (5.98%)  21/474 (4.43%) 
Injury, poisoning and procedural complications     
FALL * 1  198/468 (42.31%)  192/474 (40.51%) 
LACERATION * 1  31/468 (6.62%)  34/474 (7.17%) 
CONTUSION * 1  35/468 (7.48%)  31/474 (6.54%) 
Investigations     
WEIGHT DECREASED * 1  48/468 (10.26%)  75/474 (15.82%) 
Metabolism and nutrition disorders     
DECREASED APPETITE * 1  27/468 (5.77%)  33/474 (6.96%) 
Musculoskeletal and connective tissue disorders     
MUSCULAR WEAKNESS * 1  44/468 (9.40%)  64/474 (13.50%) 
MUSCULOSKELETAL PAIN * 1  37/468 (7.91%)  44/474 (9.28%) 
ARTHRALGIA * 1  34/468 (7.26%)  42/474 (8.86%) 
BACK PAIN * 1  36/468 (7.69%)  39/474 (8.23%) 
MUSCLE SPASMS * 1  30/468 (6.41%)  38/474 (8.02%) 
PAIN IN EXTREMITY * 1  28/468 (5.98%)  26/474 (5.49%) 
NECK PAIN * 1  9/468 (1.92%)  24/474 (5.06%) 
Nervous system disorders     
HEADACHE * 1  65/468 (13.89%)  66/474 (13.92%) 
DIZZINESS * 1  28/468 (5.98%)  42/474 (8.86%) 
AMYOTROPHIC LATERAL SCLEROSIS * 1  28/468 (5.98%)  24/474 (5.06%) 
Psychiatric disorders     
INSOMNIA * 1  60/468 (12.82%)  71/474 (14.98%) 
DEPRESSION * 1  50/468 (10.68%)  40/474 (8.44%) 
ANXIETY * 1  34/468 (7.26%)  35/474 (7.38%) 
Respiratory, thoracic and mediastinal disorders     
RESPIRATORY FAILURE * 1  81/468 (17.31%)  72/474 (15.19%) 
COUGH * 1  30/468 (6.41%)  45/474 (9.49%) 
DYSPNOEA * 1  52/468 (11.11%)  44/474 (9.28%) 
Skin and subcutaneous tissue disorders     
RASH * 1  27/468 (5.77%)  27/474 (5.70%) 
PRURITUS * 1  18/468 (3.85%)  25/474 (5.27%) 
Vascular disorders     
HYPERTENSION * 1  13/468 (2.78%)  23/474 (4.85%) 
1
Term from vocabulary, MedDRA 15.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor must be consulted
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Head of Regulatory
Organization: Knopp Biosciences
Phone: 4124881776
EMail: greg@knoppbio.com
Layout table for additonal information
Responsible Party: Knopp Biosciences
ClinicalTrials.gov Identifier: NCT01281189    
Other Study ID Numbers: 223AS302
EUDRA CT NO: 2010-022818-19
First Submitted: January 20, 2011
First Posted: January 21, 2011
Results First Submitted: December 4, 2020
Results First Posted: June 7, 2021
Last Update Posted: June 7, 2021