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Completed

NCT Number: NCT04556656

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

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

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Key information

Conditions

Huntington Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Chorea Cognition Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dementia Dyskinesias Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Mental Disorders Movement Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases

Age range

25 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Prilenia Investigational site (Site 291), Innsbruck, Austria

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

MAIN STUDY

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

Exclusion criteria

  • Use of pridopidine within 12 months before the baseline visit.
  • Gene therapy at any time
  • 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
  • History of epilepsy or seizures within the last 5 years
  • Pregnant or breastfeeding, or intention to become pregnant during the study

Treatment and study plan

pridopidine

Drug

Pridopidine hard gelatin capsule

Placebo

Drug

Pridopidine-matching placebo hard gelatin capsule

Primary outcomes

  1. Change From Baseline in the Unified Huntington Disease Rating Scale-Total Functional Capacity (UHDRS-TFC) Score (mITT)

    Time frame: From baseline to Week 65

    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.

  2. Change From Baseline to Week 65 in the UHDRS TFC Score (ITT)

    Time frame: From baseline to Week 65.

    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.

Secondary outcomes

  1. Change From Baseline to Week 65 in Composite UHDRS (cUHDRS) Total Score (mITT)

    Time frame: From baseline to Week 65

    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.

Other outcomes

  1. Change From Baseline in cUHDRS Total Score - Patients Off ADMs (mITT)

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

    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.

  2. Change From Baseline in Q-Motor Finger Tapping Inter-Onset Interval (IOI) Mean - Patients Off ADMs (mITT)

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

    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.

  3. Change From Baseline in Q-Motor Pronation/Supination Inter-Tap-Interval (ITI) Mean - Patients Off ADMs (mITT)

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

    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.

  4. Change in Q-Motor Pronation/Supination Inter-Onset-Interval (IOI) Mean - Patients Off ADMs (mITT)

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

    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.

  5. Change From Baseline in the UHDRS TFC Score - Patients Off ADMs (mITT)

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

    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.

  6. Change From Baseline in Stroop Word Reading (SWR) - Patients Off ADMs (mITT)

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

    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.

  7. Change From Baseline in Symbol Digit Modalities Test (SDMT) - Patients Off ADMs (mITT)

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

    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.

  8. Change From Baseline in Total Motor Score (TMS) - Patients Off ADMs (mITT)

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

    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.

Sponsors and collaborators

Lead sponsor

Prilenia

Industry

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2023
Study completion
2024
First posted
Sep 21, 2020
Registry last updated
Mar 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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