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

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Arm, Multicenter Study Evaluating the Efficacy and Safety of Pridopidine in Patients With Early Stage of Huntington Disease

This study will evaluate the efficacy and safety of pridopidine 45mg twice daily (BID) in patients with early stage manifest Huntington Disease (HD).

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: Pridopidine; Drug: Placebo

Detailed Description

This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pridopidine 45 mg BID in patients with early stage HD.

• Study Type: Interventional
• Enrollment (Actual): 499
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Prilenia Investigational site (Site 291)
• Canada
  • Halifax, Canada, NS B3S 1L8
    • Prilenia Investigational Site (Site 232)
  • Alberta
    • Calgary, Alberta, Canada, AB T2N 1N4
      • Prilenia Investigational Site (Site 030)
  • British Columbia
    • Vancouver, British Columbia, Canada, BC V6T 1Z4
      • Prilenia Investigational Site (Site 048)
  • Quebec
    • Montréal, Quebec, Canada, QC H2X 3E4
      • Prilenia Investigational Site (Site 098)
• Czechia
  • Prague, Czechia
    • Prilenia Investigational Site (Site 388)
• France
  • Lille, France
    • Prilenia Investigational Site (Site 385)
  • Marseille, France
    • Prilenia Investigational Site (Site 384)
  • Paris, France
    • Prilenia Investigational Site (Site 392)
• Germany
  • Aachen, Germany
    • Prilenia Investigational Site (Site 234)
  • Bochum, Germany
    • Prilenia Investigational Site (Site 379)
  • Lübeck, Germany
    • Prilenia Investigational Site (Site 377)
  • Münster, Germany
    • Prilenia Investigational Site (Site 376)
  • Taufkirchen, Germany
    • Prilenia Investigational site (Site 292)
  • Ulm, Germany
    • Prilenia Investigational Site (Site 175)
• Italy
  • Bari, Italy
    • Prilenia Investigational Site (Site 249)
  • Bologna, Italy
    • Prilenia Investigational Site (Site 394)
  • Milano, Italy
    • Prilenia Investigational Site (Site 239)
  • Napoli, Italy
    • Prilenia Investigational Site (Site 393)
  • Roma, Italy
    • Prilenia Investigational Site (Site 228)
• Netherlands
  • Leiden, Netherlands
    • Prilenia Investigational Site (Site 044)
  • Maastricht, Netherlands
    • Prilenia Investigational Site (Site 387)
• Poland
  • Gdańsk, Poland
    • Prilenia Investigational Site (Site 386)
  • Kraków, Poland
    • Prilenia Investigational Site (Site 244)
  • Warsaw, Poland
    • Prilenia Investigational Site (Site 246)
• Spain
  • Barcelona, Spain
    • Prilenia Investigational Site (Site 380)
  • Burgos, Spain
    • Prilenia Investigational Site (Site 381)
  • Madrid, Spain
    • Prilenia Investigational Site (Site 176)
  • Valencia, Spain
    • Prilenia Investigational Site (Site 382)
• United Kingdom
  • Aberdeen, United Kingdom
    • Prilenia Investigational Site (Site 180)
  • Cardiff, United Kingdom
    • Prilenia Investigational Site (Site 390)
  • Newcastle, United Kingdom
    • Prilenia Investigational Site (Site 378)
• United States
  • California
    • Davis, California, United States, 95616
      • Prilenia Investigational Site (Site 061)
    • San Diego, California, United States, 92093
      • Prilenia Investigational Site (Site 051)
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Prilenia Investigational Site (Site 343)
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Prilenia Investigational Site (Site 333)
  • Florida
    • Gainesville, Florida, United States, 32611
      • Prilenia Investigational Site (Site 160)
    • Tampa, Florida, United States, 33620
      • Prilenia Investigational Site (Site 019)
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Prilenia Investigational Site (Site 032)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Prilenia Investigational Site (Site 088)
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • Prilenia Investigational Site (Site 029)
    • Wichita, Kansas, United States, 67226
      • Prilenia Investigational Site (Site 083)
  • Kentucky
    • Louisville, Kentucky, United States, 40292
      • Prilenia Investigational Site (Site 087)
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Prilenia Investigational Site (Site 028)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Prilenia Investigational Site (Site 017)
    • Boston, Massachusetts, United States, 02215
      • Prilenia Investigational Site (Site 076)
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Prilenia Investigational Site (Site 027)
  • New York
    • Albany, New York, United States, 12208
      • Prilenia Investigational Site (Site 037)
    • New York, New York, United States, 10027
      • Prilenia Investigational Site (Site 002)
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Prilenia Investigational Site (Site 119)
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • Prilenia Investigational Site (Site 089)
    • Columbus, Ohio, United States, 43210
      • Prilenia Investigational Site (Site 020)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Prilenia Investigational Site (Site 006)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Prilenia Investigational Site (Site 018)
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Prilenia Investigational Site (Site 031)
  • Texas
    • Houston, Texas, United States, 77004
      • Prilenia Investigational Site (Site 199)
  • Virginia
    • Richmond, Virginia, United States, 23284
      • Prilenia Investigational Site (Site 326)
  • Washington
    • Seattle, Washington, United States, 98195
      • Prilenia Investigational Site (Site 096)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA MAIN STUDY

1. Diagnosis of HD based on clinical features and the presence of ≥36 CAG repeats in the huntingtin gene
2. Diagnostic confidence level (DCL) of 4
3. Adult-onset HD with onset of signs and symptoms ≥18 years of age
4. Stage 1 or Stage 2 HD, defined as a UHDRS-TFC score of ≥7, at screening

EXCLUSION CRITERIA

1. Use of pridopidine within 12 months before the baseline visit.
2. Gene therapy at any time
3. Any serious medical condition or clinically significant laboratory, or vital sign abnormality that precludes the patient's safe participation in and completion of the study e.g. significant heart disease within 12 weeks before baseline or history of certain cardiac arrhythmias
4. History of epilepsy or seizures within the last 5 years
5. Pregnant or breastfeeding, or intention to become pregnant during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; Pridopidine-matching placebo hard gelatin capsule
Experimental: Pridopidine; 45 mg pridopidine twice daily (BID)	Drug: Pridopidine; Pridopidine hard gelatin capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Unified Huntington Disease Rating Scale-Total Functional Capacity (UHDRS-TFC) Score (mITT)	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.	From baseline to Week 65
Change From Baseline to Week 65 in the UHDRS TFC Score (ITT)	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.	From baseline to Week 65.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 65 in Composite UHDRS (cUHDRS) Total Score (mITT)	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.	From baseline to Week 65

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in cUHDRS Total Score - Patients Off ADMs (mITT)	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.	Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78
Change From Baseline in Q-Motor Finger Tapping Inter-Onset Interval (IOI) Mean - Patients Off ADMs (mITT)	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.	Time course from baseline to Week 26, Week 52, Week 65, and Week 78.
Change From Baseline in Q-Motor Pronation/Supination Inter-Tap-Interval (ITI) Mean - Patients Off ADMs (mITT)	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.	Time course from baseline to Week 26, Week 52, Week 65, and Week 78.
Change in Q-Motor Pronation/Supination Inter-Onset-Interval (IOI) Mean - Patients Off ADMs (mITT)	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.	Time course from baseline to Week 26, Week 52, Week 65, and Week 78.
Change From Baseline in the UHDRS TFC Score - Patients Off ADMs (mITT)	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.	Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78
Change From Baseline in Stroop Word Reading (SWR) - Patients Off ADMs (mITT)	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.	Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78
Change From Baseline in Symbol Digit Modalities Test (SDMT) - Patients Off ADMs (mITT)	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.	Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78.
Change From Baseline in Total Motor Score (TMS) - Patients Off ADMs (mITT)	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.	Time course from baseline to Week 26, Week 39, Week 52, Week 65, and Week 78.

Collaborators and Investigators

• Sponsor: Prilenia
• Investigators: Study Director: Yael Cohen, Prilenia

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2020
• Primary Completion (Actual): March 14, 2023
• Study Completion (Actual): March 21, 2024

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Huntington Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Genetic Diseases, Inborn; Neurocognitive Disorders; Cognition Disorders; Dementia; Neurodegenerative Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Dyskinesias; Chorea; Huntington Disease
• Other Study ID Numbers: PL101-HD301; 2020-002822-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No