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

NCT04556656 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: PL101-HD3012020-002822-10
• Study Type: interventional
• Target: 499
• Locations: 11 countries
• Sites: 58

Brief Summary

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

Conditions

Huntington Disease

Keywords

Huntington Disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

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

  From baseline to Week 65

Other Outcomes (8)

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

  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)

  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)

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

Study Arms (2)

Pridopidine

EXPERIMENTAL

45 mg pridopidine twice daily (BID)

Drug: Pridopidine

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

Pridopidine DRUG

Pridopidine hard gelatin capsule

Pridopidine

Placebo DRUG

Pridopidine-matching placebo hard gelatin capsule

Placebo

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prilenia: lead

Study Sites (58)

Prilenia Investigational Site (Site 061)

Davis, California, 95616, United States

Location

Prilenia Investigational Site (Site 051)

San Diego, California, 92093, United States

Location

Prilenia Investigational Site (Site 343)

Englewood, Colorado, 80113, United States

Location

Prilenia Investigational Site (Site 333)

Washington D.C., District of Columbia, 20057, United States

Location

Prilenia Investigational Site (Site 160)

Gainesville, Florida, 32611, United States

Location

Prilenia Investigational Site (Site 019)

Tampa, Florida, 33620, United States

Location

Prilenia Investigational Site (Site 032)

Atlanta, Georgia, 30322, United States

Location

Prilenia Investigational Site (Site 088)

Chicago, Illinois, 60611, United States

Location

Prilenia Investigational Site (Site 029)

Kansas City, Kansas, 66103, United States

Location

Prilenia Investigational Site (Site 083)

Wichita, Kansas, 67226, United States

Location

Prilenia Investigational Site (Site 087)

Louisville, Kentucky, 40292, United States

Location

Prilenia Investigational Site (Site 028)

Baltimore, Maryland, 21218, United States

Location

Prilenia Investigational Site (Site 017)

Boston, Massachusetts, 02114, United States

Location

Prilenia Investigational Site (Site 076)

Boston, Massachusetts, 02215, United States

Location

Prilenia Investigational Site (Site 027)

St Louis, Missouri, 63130, United States

Location

Prilenia Investigational Site (Site 037)

Albany, New York, 12208, United States

Location

Prilenia Investigational Site (Site 002)

New York, New York, 10027, United States

Location

Prilenia Investigational Site (Site 119)

Durham, North Carolina, 27708, United States

Location

Prilenia Investigational Site (Site 089)

Cincinnati, Ohio, 45221, United States

Location

Prilenia Investigational Site (Site 020)

Columbus, Ohio, 43210, United States

Location

Prilenia Investigational Site (Site 006)

Portland, Oregon, 97239, United States

Location

Prilenia Investigational Site (Site 018)

Philadelphia, Pennsylvania, 19104, United States

Location

Prilenia Investigational Site (Site 031)

Nashville, Tennessee, 37232, United States

Location

Prilenia Investigational Site (Site 199)

Houston, Texas, 77004, United States

Location

Prilenia Investigational Site (Site 326)

Richmond, Virginia, 23284, United States

Location

Prilenia Investigational Site (Site 096)

Seattle, Washington, 98195, United States

Location

Prilenia Investigational site (Site 291)

Innsbruck, Austria

Location

Prilenia Investigational Site (Site 030)

Calgary, Alberta, AB T2N 1N4, Canada

Location

Prilenia Investigational Site (Site 048)

Vancouver, British Columbia, BC V6T 1Z4, Canada

Location

Prilenia Investigational Site (Site 098)

Montreal, Quebec, QC H2X 3E4, Canada

Location

Prilenia Investigational Site (Site 232)

Halifax, NS B3S 1L8, Canada

Location

Prilenia Investigational Site (Site 388)

Prague, Czechia

Location

Prilenia Investigational Site (Site 385)

Lille, France

Location

Prilenia Investigational Site (Site 384)

Marseille, France

Location

Prilenia Investigational Site (Site 392)

Paris, France

Location

Prilenia Investigational Site (Site 234)

Aachen, Germany

Location

Prilenia Investigational Site (Site 379)

Bochum, Germany

Location

Prilenia Investigational Site (Site 377)

Lübeck, Germany

Location

Prilenia Investigational Site (Site 376)

Münster, Germany

Location

Prilenia Investigational site (Site 292)

Taufkirchen, Germany

Location

Prilenia Investigational Site (Site 175)

Ulm, Germany

Location

Prilenia Investigational Site (Site 249)

Bari, Italy

Location

Prilenia Investigational Site (Site 394)

Bologna, Italy

Location

Prilenia Investigational Site (Site 239)

Milan, Italy

Location

Prilenia Investigational Site (Site 393)

Napoli, Italy

Location

Prilenia Investigational Site (Site 228)

Roma, Italy

Location

Prilenia Investigational Site (Site 044)

Leiden, Netherlands

Location

Prilenia Investigational Site (Site 387)

Maastricht, Netherlands

Location

Prilenia Investigational Site (Site 386)

Gdansk, Poland

Location

Prilenia Investigational Site (Site 244)

Krakow, Poland

Location

Prilenia Investigational Site (Site 246)

Warsaw, Poland

Location

Prilenia Investigational Site (Site 380)

Barcelona, Spain

Location

Prilenia Investigational Site (Site 381)

Burgos, Spain

Location

Prilenia Investigational Site (Site 176)

Madrid, Spain

Location

Prilenia Investigational Site (Site 382)

Valencia, Spain

Location

Prilenia Investigational Site (Site 180)

Aberdeen, United Kingdom

Location

Prilenia Investigational Site (Site 390)

Cardiff, United Kingdom

Location

Prilenia Investigational Site (Site 378)

Newcastle, United Kingdom

Location

Related Publications (1)

• Reilmann R, Feigin A, Rosser AE, Kostyk SK, Saft C, Cohen Y, Schuring H, Hand R, Tan AM, Chen K, Feng W, Navon-Perry L, Cruz-Herranz A, Syltevik C, Boot D, Squitieri F, Kayson E, Mehra M, Goldberg YP, Geva M, Hayden MR; PROOF-HD study investigators. Pridopidine in early-stage manifest Huntington's disease: a phase 3 trial. Nat Med. 2025 Nov;31(11):3780-3789. doi: 10.1038/s41591-025-03920-3. Epub 2025 Sep 5.

  PMID: 40913168 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

pridopidine

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Prilenia
• Organization: Prilenia

info@prilenia.com

+972 775558

Study Officials

• Yael Cohen

  Prilenia

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 21, 2020
• Study Start: October 16, 2020
• Primary Completion: March 14, 2023
• Study Completion: March 21, 2024
• Last Updated: March 12, 2025
• Results First Posted: March 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); DE (6); ES (4); AU (1); IT (5); CZ (1); NL (2); FR (3); US (26); CA (4); PL (3)