Trial Outcomes & Findings for PRidopidine's Outcome On Function in Huntington Disease, PROOF- HD (NCT NCT04556656)

NCT ID: NCT04556656

Last Updated: 2025-03-12

Results Overview

The primary efficacy endpoint for this study was the change from baseline to Week 65 in the TFC (defined as the sum of all TFC 5-items ratings \[domestic chores, activities of daily living, finances, care level, and occupation\]). The TFC is the standard and well-accepted clinical scale for staging and tracking the progression of HD using functional capacity. Scores range from 0 to 13, with 13 as the least affected and 0 as complete incapacity.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

499 participants

Primary outcome timeframe

From baseline to Week 65

Results posted on

2025-03-12

Participant Flow

Participant milestones

Participant milestones
Measure
Pridopidine
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Overall Study
STARTED
250
249
Overall Study
COMPLETED
222
227
Overall Study
NOT COMPLETED
28
22

Reasons for withdrawal

Reasons for withdrawal
Measure
Pridopidine
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Overall Study
Withdrawal by Subject
14
12
Overall Study
Physician Decision
1
0
Overall Study
Adverse Event
4
7
Overall Study
Death
4
0
Overall Study
Lost to Follow-up
3
2
Overall Study
Not further specified
2
1

Baseline Characteristics

PRidopidine's Outcome On Function in Huntington Disease, PROOF- HD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Pridopidine
n=250 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=249 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Total
n=499 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
207 Participants
n=5 Participants
213 Participants
n=7 Participants
420 Participants
n=5 Participants
Age, Categorical
>=65 years
43 Participants
n=5 Participants
36 Participants
n=7 Participants
79 Participants
n=5 Participants
Age, Continuous
52.2 years
STANDARD_DEVIATION 11.93 • n=5 Participants
52.7 years
STANDARD_DEVIATION 11.39 • n=7 Participants
52.5 years
STANDARD_DEVIATION 11.66 • n=5 Participants
Sex: Female, Male
Female
132 Participants
n=5 Participants
127 Participants
n=7 Participants
259 Participants
n=5 Participants
Sex: Female, Male
Male
118 Participants
n=5 Participants
122 Participants
n=7 Participants
240 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
Race (NIH/OMB)
White
242 Participants
n=5 Participants
235 Participants
n=7 Participants
477 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
5 Participants
n=5 Participants
9 Participants
n=7 Participants
14 Participants
n=5 Participants
Region of Enrollment
Canada
9 participants
n=5 Participants
17 participants
n=7 Participants
26 participants
n=5 Participants
Region of Enrollment
Austria
5 participants
n=5 Participants
6 participants
n=7 Participants
11 participants
n=5 Participants
Region of Enrollment
Netherlands
14 participants
n=5 Participants
8 participants
n=7 Participants
22 participants
n=5 Participants
Region of Enrollment
United States
108 participants
n=5 Participants
93 participants
n=7 Participants
201 participants
n=5 Participants
Region of Enrollment
Czechia
6 participants
n=5 Participants
8 participants
n=7 Participants
14 participants
n=5 Participants
Region of Enrollment
Poland
16 participants
n=5 Participants
15 participants
n=7 Participants
31 participants
n=5 Participants
Region of Enrollment
Italy
28 participants
n=5 Participants
30 participants
n=7 Participants
58 participants
n=5 Participants
Region of Enrollment
United Kingdom
5 participants
n=5 Participants
13 participants
n=7 Participants
18 participants
n=5 Participants
Region of Enrollment
France
4 participants
n=5 Participants
7 participants
n=7 Participants
11 participants
n=5 Participants
Region of Enrollment
Germany
37 participants
n=5 Participants
41 participants
n=7 Participants
78 participants
n=5 Participants
Region of Enrollment
Spain
18 participants
n=5 Participants
11 participants
n=7 Participants
29 participants
n=5 Participants
HD stage at randomization
HD1
102 Participants
n=5 Participants
103 Participants
n=7 Participants
205 Participants
n=5 Participants
HD stage at randomization
HD2
148 Participants
n=5 Participants
146 Participants
n=7 Participants
294 Participants
n=5 Participants

PRIMARY outcome

Timeframe: From baseline to Week 65

Population: The modified intent to treat (mITT) population included all participants in the ITT population who received at least one dose of study drug and had valid in clinic TFC scores both at baseline and at least one post-baseline timepoint. The mITT population was analyzed according to the treatment to which the participant was randomized. The mITT population was the main analysis population for the primary endpoint in non-EMA regions. Note that the analysis was based on observed data.

The primary efficacy endpoint for this study was the change from baseline to Week 65 in the TFC (defined as the sum of all TFC 5-items ratings \[domestic chores, activities of daily living, finances, care level, and occupation\]). The TFC is the standard and well-accepted clinical scale for staging and tracking the progression of HD using functional capacity. Scores range from 0 to 13, with 13 as the least affected and 0 as complete incapacity.

Outcome measures

Outcome measures
Measure
Pridopidine
n=243 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=247 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline in the Unified Huntington Disease Rating Scale-Total Functional Capacity (UHDRS-TFC) Score (mITT)
-1.18 score on a scale
Standard Error 0.119
-0.95 score on a scale
Standard Error 0.119

PRIMARY outcome

Timeframe: From baseline to Week 65.

Population: The intent to treat (ITT) population included all randomized participants. The ITT population was analyzed according to the treatment to which the participant was randomized. The ITT population was the main analysis population for the primary endpoint in the EMA region.

The primary efficacy endpoint for this study was the change from baseline to Week 65 in the TFC (defined as the sum of all TFC 5-items ratings \[domestic chores, activities of daily living, finances, care level, and occupation\]). The TFC is the standard and well-accepted clinical scale for staging and tracking the progression of HD using functional capacity. Scores range from 0 to 13, with 13 as the least affected and 0 as complete incapacity.

Outcome measures

Outcome measures
Measure
Pridopidine
n=250 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=249 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline to Week 65 in the UHDRS TFC Score (ITT)
-1.17 score on a scale
Standard Error 0.120
-0.94 score on a scale
Standard Error 0.120

SECONDARY outcome

Timeframe: From baseline to Week 65

Population: The modified intent to treat (mITT) population included all participants in the ITT population who received at least one dose of study drug and had valid in-clinic TFC scores both at baseline and at least one post-baseline timepoint. The mITT population was analyzed according to the treatment to which the participant was randomized. Note that the analysis was based on as observed data only, patient numbers are therefore lower.

The composite Unified Huntington Disease Rating Scale (cUHDRS) uses 4 components: Total Motor Score (TMS) assesses motor features (oculomotor, dysarthria, chorea, dystonia, gait, postural stability). Higher score = worse outcome. Best score=0. Worst score= 124. Stroop Word Reading (SWR) measures attention and mental flexibility. Pat. reads names of colors printed in black ink. Scores reflect correct responses in 45 sec. Higher score = better outcome. Best score=100. Worst score=0. Symbol Digit Modalities Test (SDMT) tests psychomotor speed and working memory. Participant has 90 sec to match numbers with symbols. Scores = correct answers in 90 sec. Higher score = better outcome. Best score=120. Worst score=0. Total Functional Capacity (TFC) tests the capacity to maintain daily living, finances, care level, occupation. Higher score = better outcome. Best score=13. Worst score=0. Total integrated cUHDRS scale range: -7.6 to 24.8. The higher, the better.

Outcome measures

Outcome measures
Measure
Pridopidine
n=243 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=247 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline to Week 65 in Composite UHDRS (cUHDRS) Total Score (mITT)
-0.99 score on a scale
Standard Error 0.109
-0.88 score on a scale
Standard Error 0.108

OTHER_PRE_SPECIFIED outcome

Timeframe: Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78

Population: The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

The composite Unified Huntington Disease Rating Scale (cUHDRS) assesses 4 components (see secondary outcome for details): Total Motor Score (TMS) for motor features. Higher score = worse outcome. Worst = 124. Stroop Word Reading (SWR) measures attention and mental flexibility. Higher score = better outcome. Symbol Digit Modalities Test (SDMT) tests psychomotor speed and working memory. Higher score = better outcome. Total Functional Capacity (TFC) tests the capacity to maintain daily living, finances, care level, occupation. The higher, the better. Total cUHDRS scale range: -7.6 to 24.8 (assuming 150 as the max score of SWR). The higher, the better. This sensitivity analysis was performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Outcome measures

Outcome measures
Measure
Pridopidine
n=97 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=112 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline in cUHDRS Total Score - Patients Off ADMs (mITT)
Week 26
0.15 score on a scale
Standard Error 0.114
-0.31 score on a scale
Standard Error 0.108
Change From Baseline in cUHDRS Total Score - Patients Off ADMs (mITT)
Week 39
0.10 score on a scale
Standard Error 0.130
-0.34 score on a scale
Standard Error 0.125
Change From Baseline in cUHDRS Total Score - Patients Off ADMs (mITT)
Week 52
-0.07 score on a scale
Standard Error 0.140
-0.48 score on a scale
Standard Error 0.135
Change From Baseline in cUHDRS Total Score - Patients Off ADMs (mITT)
Week 65
-0.26 score on a scale
Standard Error 0.143
-0.53 score on a scale
Standard Error 0.137
Change From Baseline in cUHDRS Total Score - Patients Off ADMs (mITT)
Week 78
-0.40 score on a scale
Standard Error 0.159
-0.54 score on a scale
Standard Error 0.158

OTHER_PRE_SPECIFIED outcome

Timeframe: Time course from baseline to Week 26, Week 52, Week 65, and Week 78.

Population: The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Quantitative (Q)-motor is a clinical assessment of fine motor skills. It is based on the application of pre-calibrated and temperature-controlled force transducers and 3-dimensional position sensors. The index finger is positioned above a force transducer and is to tap as fast as possible. The start was defined as a rise of the force by 0.05 Newton above maximal baseline level. The tap ended when it dropped to 0.05 N before the maximal baseline level was reached again. The IOI refers to the time between the onset of consecutive taps (the faster, the better). In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Outcome measures

Outcome measures
Measure
Pridopidine
n=97 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=112 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline in Q-Motor Finger Tapping Inter-Onset Interval (IOI) Mean - Patients Off ADMs (mITT)
Week 26
-14.85 milliseconds (decrease = improvement)
Standard Error 6.846
6.30 milliseconds (decrease = improvement)
Standard Error 6.449
Change From Baseline in Q-Motor Finger Tapping Inter-Onset Interval (IOI) Mean - Patients Off ADMs (mITT)
Week 52
-2.37 milliseconds (decrease = improvement)
Standard Error 7.135
11.95 milliseconds (decrease = improvement)
Standard Error 6.792
Change From Baseline in Q-Motor Finger Tapping Inter-Onset Interval (IOI) Mean - Patients Off ADMs (mITT)
Week 65
-0.79 milliseconds (decrease = improvement)
Standard Error 7.365
23.93 milliseconds (decrease = improvement)
Standard Error 7.028
Change From Baseline in Q-Motor Finger Tapping Inter-Onset Interval (IOI) Mean - Patients Off ADMs (mITT)
Week 78
1.46 milliseconds (decrease = improvement)
Standard Error 7.444
24.36 milliseconds (decrease = improvement)
Standard Error 7.230

OTHER_PRE_SPECIFIED outcome

Timeframe: Time course from baseline to Week 26, Week 52, Week 65, and Week 78.

Population: The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Quantitative (Q)-motor is a clinical assessment of fine motor skills that are crucial for daily activities. It is based on the application of pre-calibrated and temperature-controlled force transducers and 3-dimensional position sensors. Pronation/Supination assesses the regularity of hand taps. The force and duration of the hand taps were recorded similarly to the speeded tapping task. One pronation/supination hand tapping measure is ITI (the faster, the better). In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Outcome measures

Outcome measures
Measure
Pridopidine
n=97 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=112 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline in Q-Motor Pronation/Supination Inter-Tap-Interval (ITI) Mean - Patients Off ADMs (mITT)
Week 26
-17.63 milliseconds
Standard Error 8.029
20.43 milliseconds
Standard Error 7.448
Change From Baseline in Q-Motor Pronation/Supination Inter-Tap-Interval (ITI) Mean - Patients Off ADMs (mITT)
Week 52
-0.15 milliseconds
Standard Error 9.124
20.07 milliseconds
Standard Error 8.555
Change From Baseline in Q-Motor Pronation/Supination Inter-Tap-Interval (ITI) Mean - Patients Off ADMs (mITT)
Week 65
4.64 milliseconds
Standard Error 8.380
28.55 milliseconds
Standard Error 7.867
Change From Baseline in Q-Motor Pronation/Supination Inter-Tap-Interval (ITI) Mean - Patients Off ADMs (mITT)
Week 78
12.73 milliseconds
Standard Error 9.740
34.97 milliseconds
Standard Error 9.412

OTHER_PRE_SPECIFIED outcome

Timeframe: Time course from baseline to Week 26, Week 52, Week 65, and Week 78.

Population: The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Quantitative (Q)-motor is a clinical assessment of fine motor skills that are crucial for daily activities. It is based on the application of pre-calibrated and temperature-controlled force transducers and 3-dimensional position sensors. Pronation/Supination assess the regularity of hand taps. The force and duration of the hand taps were recorded similarly to the speeded tapping task. One pronation/supination hand tapping measure is IOI (the faster, the better). In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Outcome measures

Outcome measures
Measure
Pridopidine
n=97 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=112 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change in Q-Motor Pronation/Supination Inter-Onset-Interval (IOI) Mean - Patients Off ADMs (mITT)
Week 26
-16.70 milliseconds
Standard Error 9.399
13.68 milliseconds
Standard Error 8.829
Change in Q-Motor Pronation/Supination Inter-Onset-Interval (IOI) Mean - Patients Off ADMs (mITT)
Week 52
7.40 milliseconds
Standard Error 10.978
24.23 milliseconds
Standard Error 10.467
Change in Q-Motor Pronation/Supination Inter-Onset-Interval (IOI) Mean - Patients Off ADMs (mITT)
Week 65
7.34 milliseconds
Standard Error 10.730
30.13 milliseconds
Standard Error 10.232
Change in Q-Motor Pronation/Supination Inter-Onset-Interval (IOI) Mean - Patients Off ADMs (mITT)
Week 78
19.21 milliseconds
Standard Error 12.702
41.93 milliseconds
Standard Error 12.435

OTHER_PRE_SPECIFIED outcome

Timeframe: Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78

Population: The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Total Functional Capacity (TFC) tests the capacity to maintain domestic chores, activities of daily living, finances, care level, and occupation. Scores from 0 - 13. Higher score = better outcome. In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Outcome measures

Outcome measures
Measure
Pridopidine
n=97 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=112 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline in the UHDRS TFC Score - Patients Off ADMs (mITT)
Week 26
-0.01 score on a scale
Standard Error 0.131
-0.23 score on a scale
Standard Error 0.124
Change From Baseline in the UHDRS TFC Score - Patients Off ADMs (mITT)
Week 39
-0.11 score on a scale
Standard Error 0.137
-0.31 score on a scale
Standard Error 0.131
Change From Baseline in the UHDRS TFC Score - Patients Off ADMs (mITT)
Week 52
-0.19 score on a scale
Standard Error 0.149
-0.45 score on a scale
Standard Error 0.143
Change From Baseline in the UHDRS TFC Score - Patients Off ADMs (mITT)
Week 65
-0.49 score on a scale
Standard Error 0.156
-0.54 score on a scale
Standard Error 0.150
Change From Baseline in the UHDRS TFC Score - Patients Off ADMs (mITT)
Week 78
-0.42 score on a scale
Standard Error 0.166
-0.54 score on a scale
Standard Error 0.163

OTHER_PRE_SPECIFIED outcome

Timeframe: Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78

Population: The mITT population was used for subgroup analyses. Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Stroop Word Reading (SWR) measures attention and mental flexibility. Pat. reads names of colors printed in black ink. Scores reflect correct responses in 45 sec. Higher score = better outcome. In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Outcome measures

Outcome measures
Measure
Pridopidine
n=97 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=112 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline in Stroop Word Reading (SWR) - Patients Off ADMs (mITT)
Week 26
2.34 score on a scale
Standard Error 0.964
-0.82 score on a scale
Standard Error 0.916
Change From Baseline in Stroop Word Reading (SWR) - Patients Off ADMs (mITT)
Week 39
2.85 score on a scale
Standard Error 1.100
-0.04 score on a scale
Standard Error 1.051
Change From Baseline in Stroop Word Reading (SWR) - Patients Off ADMs (mITT)
Week 52
2.73 score on a scale
Standard Error 1.078
-0.32 score on a scale
Standard Error 1.039
Change From Baseline in Stroop Word Reading (SWR) - Patients Off ADMs (mITT)
Week 65
1.39 score on a scale
Standard Error 1.243
-0.94 score on a scale
Standard Error 1.193
Change From Baseline in Stroop Word Reading (SWR) - Patients Off ADMs (mITT)
Week 78
0.91 score on a scale
Standard Error 1.261
-1.08 score on a scale
Standard Error 1.249

OTHER_PRE_SPECIFIED outcome

Timeframe: Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78.

Population: Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Symbol Digit Modalities Test (SDMT) tests psychomotor speed and working memory. Participant has 90 sec to write match numbers with symbols. Scoring sums correct substitutions in 90 second interval (max = 110). Higher score = better outcome. In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Outcome measures

Outcome measures
Measure
Pridopidine
n=97 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=112 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline in Symbol Digit Modalities Test (SDMT) - Patients Off ADMs (mITT)
Week 26
0.54 score on a scale
Standard Error 0.521
-0.47 score on a scale
Standard Error 0.484
Change From Baseline in Symbol Digit Modalities Test (SDMT) - Patients Off ADMs (mITT)
Week 39
0.82 score on a scale
Standard Error 0.512
-0.06 score on a scale
Standard Error 0.478
Change From Baseline in Symbol Digit Modalities Test (SDMT) - Patients Off ADMs (mITT)
Week 52
-0.42 score on a scale
Standard Error 0.578
-0.33 score on a scale
Standard Error 0.543
Change From Baseline in Symbol Digit Modalities Test (SDMT) - Patients Off ADMs (mITT)
Week 65
0.35 score on a scale
Standard Error 0.616
0.07 score on a scale
Standard Error 0.576
Change From Baseline in Symbol Digit Modalities Test (SDMT) - Patients Off ADMs (mITT)
Week 78
0.07 score on a scale
Standard Error 0.617
-0.36 score on a scale
Standard Error 0.598

OTHER_PRE_SPECIFIED outcome

Timeframe: Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78.

Population: Note: Analyses/p-values were generated on observed data. Patient numbers at individual weeks varied.

Total Motor Score (TMS) assesses motor features (oculomotor, dysarthria, chorea, dystonia, gait, postural stability). Each rated 0 (normal) - 4 (abnormal). Higher score = worse outcome. Worst = 124. In addition to the main efficacy analyses, sensitivity analyses were performed in a sub-group of patients who were off neuroleptics AND off vesicular monoamine transporter-2 (VMAT2) inhibitors (together called antidopaminergics, or ADMs) at any time during the study.

Outcome measures

Outcome measures
Measure
Pridopidine
n=97 Participants
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=112 Participants
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Change From Baseline in Total Motor Score (TMS) - Patients Off ADMs (mITT)
Week 26
-0.21 score on a scale
Standard Error 0.568
-0.03 score on a scale
Standard Error 0.530
Change From Baseline in Total Motor Score (TMS) - Patients Off ADMs (mITT)
Week 39
0.06 score on a scale
Standard Error 0.780
0.96 score on a scale
Standard Error 0.729
Change From Baseline in Total Motor Score (TMS) - Patients Off ADMs (mITT)
Week 52
0.47 score on a scale
Standard Error 0.766
0.80 score on a scale
Standard Error 0.720
Change From Baseline in Total Motor Score (TMS) - Patients Off ADMs (mITT)
Week 65
0.92 score on a scale
Standard Error 0.847
1.28 score on a scale
Standard Error 0.790
Change From Baseline in Total Motor Score (TMS) - Patients Off ADMs (mITT)
Week 78
2.19 score on a scale
Standard Error 0.954
1.63 score on a scale
Standard Error 0.916

Adverse Events

Pridopidine

Serious events: 34 serious events
Other events: 204 other events
Deaths: 4 deaths

Placebo

Serious events: 21 serious events
Other events: 212 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
Pridopidine
n=250 participants at risk
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=249 participants at risk
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Psychiatric disorders
Suicidal ideation
0.80%
2/250 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.80%
2/249 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Anxiety
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.80%
2/249 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Suicide attempt
1.2%
3/250 • Number of events 3 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Delusion
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Paranoia
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Psychotic disorder
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Anxiety disorder
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Depression
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Irritability
0.40%
1/250 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Fall
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.80%
2/249 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Accident
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Brain contusion
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Facial bones fracture
0.40%
1/250 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Fibula fracture
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Head injury
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Limb injury
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Patella fracture
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Road traffic accident
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Spinal cord injury cervical
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Subdural hematoma
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Tibia fracture
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
COVID-19
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
COVID-19 pneumonia
0.80%
2/250 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
Appendicitis perforated
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
Bronchitis
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
Pneumonia
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
Sepsis
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
0.80%
2/250 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Spinal cord neoplasm
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Gastrointestinal disorders
Dysphagia
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Gastrointestinal disorders
Gastrointestinal hemorrhage
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Gastrointestinal disorders
Gastrointestinal polyp hemorrhage
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Gastrointestinal disorders
Hematemesis
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Nervous system disorders
Syncope
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.80%
2/249 • Number of events 3 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Nervous system disorders
Ataxia
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Nervous system disorders
Chorea
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Nervous system disorders
Radiculopathy
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Cardiac disorders
Acute myocardial infarction
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
1.2%
3/249 • Number of events 3 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Cardiac disorders
Aortic valve incompetence
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Musculoskeletal and connective tissue disorders
Back pain
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Musculoskeletal and connective tissue disorders
Spinal stenosis
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
General disorders
Death
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
General disorders
Gait disturbance
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Metabolism and nutrition disorders
Hyponatremia
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Metabolism and nutrition disorders
Malnutrition
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Blood and lymphatic system disorders
Microcytic anemia
0.00%
0/250 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.40%
1/249 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Hepatobiliary disorders
Cholecystitis
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Investigations
Weight decreased
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Respiratory, thoracic and mediastinal disorders
Epistaxis
0.40%
1/250 • Number of events 1 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Vascular disorders
Hematoma
0.40%
1/250 • Number of events 2 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
0.00%
0/249 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).

Other adverse events

Other adverse events
Measure
Pridopidine
n=250 participants at risk
45 mg pridopidine twice daily (BID) Pridopidine: Pridopidine hard gelatin capsule
Placebo
n=249 participants at risk
Matching placebo Placebo: Pridopidine-matching placebo hard gelatin capsule
Investigations
Weight decreased
5.2%
13/250 • Number of events 13 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
2.8%
7/249 • Number of events 7 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Fall
22.0%
55/250 • Number of events 114 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
22.9%
57/249 • Number of events 111 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Injury, poisoning and procedural complications
Contusion
4.8%
12/250 • Number of events 20 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
5.6%
14/249 • Number of events 15 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Nervous system disorders
Headache
6.4%
16/250 • Number of events 18 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
10.0%
25/249 • Number of events 34 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Gastrointestinal disorders
Diarrhea
8.4%
21/250 • Number of events 27 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
8.8%
22/249 • Number of events 32 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Depression
10.4%
26/250 • Number of events 27 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
4.8%
12/249 • Number of events 16 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Psychiatric disorders
Anxiety
7.6%
19/250 • Number of events 22 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
6.4%
16/249 • Number of events 20 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Musculoskeletal and connective tissue disorders
Back pain
4.8%
12/250 • Number of events 13 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
5.6%
14/249 • Number of events 16 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
COVID-19
23.6%
59/250 • Number of events 62 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
22.9%
57/249 • Number of events 66 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
Nasopharyngitis
7.6%
19/250 • Number of events 22 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
7.2%
18/249 • Number of events 20 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
Infections and infestations
Urinary tract infection
4.4%
11/250 • Number of events 12 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).
6.8%
17/249 • Number of events 20 • From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).

Additional Information

Prilenia

Prilenia

Phone: +972 775558

Results disclosure agreements

  • Principal investigator is a sponsor employee PIs are not employed by the organization sponsoring the study. There is an agreement between PIs and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. Data and results are owned by the sponsor. Results can be used by the institution for (a) internal noncommercial research, education and patient care, and (b) as required under applicable laws and regulations. Other uses require prior written consent of the sponsor.
  • Publication restrictions are in place

Restriction type: OTHER