Pridopidine Phase 3 Study in Huntington's Disease

Official title

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Pridopidine in Participants With Huntington's Disease (HD)

Overview

The goal of this clinical trial is to learn if pridopidine can slow the clinical decline of Huntington's Disease (HD) in adult participants. It will also inform about the safety of pridopidine. The main questions the study aims to answer are: Does pridopidine slow the overall worsening of HD over 1 year? Does pridopidine slow the worsening of specific aspects of HD over 1 year, namely the clinical progression, the ability to perform daily life activities (functional capacity), the mind's ability to process information (cognition), working of the muscles (motor function), and quality of life? Researchers will compare the drug pridopidine to a placebo (a look-alike substance that contains no drug) to see if pridopidine works better than placebo to treat HD. During the first year of the study, participants will have the same chance to receive either pridopidine or placebo. Participants will: Take 1 pridopidine or placebo capsule twice daily for 12 months. Visit the clinic 6 times within 1 year for checkups and tests. All participants who complete this 1-year placebo-controlled study period will roll over into an additional 2-year study period during which all participants will receive pridopidine treatment, including participants who had received placebo during the first year. During this additional 2-year treatment period participants will visit the clinic a total of 6 times for checkups and tests.

Detailed description

This Phase 3 study consists of two study periods, a randomized, double-blind, placebo-controlled 1-year study period and a 2-year open-label extension (OLE) period. The study assesses the effect of pridopidine 45 mg twice daily on HD in participants who are not using antidopaminergic medications (ADMs) at study start. Main objectives of the study will be to assess the effect of pridopidine on clinical progression of HD within 1 year and to evaluate the effect of pridopidine on functional capacity, cognition, motor function, quality of life (QoL), and speech in participants with HD within 1 year.

The target population in this study are adult participants (age 23-65, inclusive) with adult-onset HD (onset of signs and symptoms and a diagnosis ≥21 years of age). Eligible participants have not been using ADMs for at least 6 months prior to the screening visit. In case ADM treatment is deemed necessary by the treating physician during the study, specific ADMs and doses may be initiated. Female participants who are pregnant, planning to become pregnant or breastfeeding are not allowed to enter the study.

The treatment period will start with a 2-week titration period of once-daily treatment (1 capsule of pridopidine or placebo taken orally in the morning). From Day 15 onwards, all participants will take the study drug twice daily: in the morning and in the afternoon. Treatment will continue for an additional 50 weeks.

The placebo-controlled study period includes 6 in-clinic visits and 5 telephone visits (safety calls) during the 1-year treatment period.

The placebo-controlled study period will be followed by a 2-year OLE period. During the OLE period, all eligible participants will receive pridopidine. The OLE will consist of a 2-year treatment period, including an initial 2-week (re)titration period for all participants at pridopidine once daily and a maintenance period of 102 weeks with pridopidine twice daily. The blinding of the original treatment assignment will be maintained for all participants and study personnel during the OLE period.

A total of 6 in-clinic visits and 6 telephone visits (safety calls) are planned during the 2-year OLE period.

Interventions

• Drug Pridopidine
  Pridopidine hard gelatin capsule
• Drug Placebo
  Matched placebo hard gelatin capsule

Primary outcome measures

• Change in Composite Unified Huntington's Disease Rating Scale (cUHDRS) [Time frame: Change from Baseline to Week 52]

Secondary outcome measures (3)

• Change in Total Functional Capacity (TFC) score [Time frame: Change from Baseline to Week 52]
• Change in Quantitative Motor (Q-Motor) Finger Tapping Inter-Onset Interval (FT-IOI) mean [Time frame: Change from Baseline to Week 52]
• Change in Stroop Word Reading (SWR) score [Time frame: Change from Baseline to Week 52]

Eligibility criteria

Inclusion criteria

• Adult-onset HD (onset of signs and symptoms and a clinical diagnosis at ≥21 years of age).
• A diagnosis based on clinical features and the presence of ≥40 CAG repeats in the huntingtin (HTT) gene confirmed by historical laboratory quanitified results or by a diagnostic test at Screening.
• Diagnostic confidence level (DCL) of 4 (DCL=4 unequivocal motor signs, ≥99% confidence) on the standardized motor exam Total Motor Score (TMS).
• Total Functional Capacity (TFC) score of ≥7 at Screening and Baseline.
• Cytosine-Adenine-Guanine (CAG)-Age Product (CAP)100 score ≥95 at Screening.
• Independence Scale (IS) score ≤90% at Screening.
• Total Motor Score (TMS) of ≥20 at Screening and Baseline.
• Not using ADMs (VMAT2i and neuroleptics/antipsychotics) for at least 6 months prior to Screening visit. Importantly, it is not encouraged to discontinue the participants' ADM treatment solely for enrollment in the current trial.

Exclusion criteria

• Clinically significant cardiovascular disease (e.g. QTcF >450 msec \[males\] or >470 msec \[females\], arrhythmias, uncontrolled atrial fibrillation, or congenital long QT syndrome), seizure history ≤5 years, significant neurological disorders (e.g. intracranial pathology or cerebrovascular events), active/recent malignancy (unless localized and resolved), or any serious or uncontrolled systemic disease (e.g. hepatic, renal, respiratory, endocrine, infectious \[HBV, HCV, HIV\], or psychiatric) that may pose safety risk or interfere with participation.
• Severe hepatic or renal impairment.
• Any mutant huntingtin (mHTT) lowering therapy in the past year.
• Medications that prolong QT interval, taken within 4 weeks of the baseline visit.
• Use of pridopidine within 6 weeks or 5 half-lives before the screening visit.
• Previous participation in intracranial gene therapy study.
• Laboratory values that fall outside of the central laboratory's reference range at Screening and are considered clinically significantly abnormal by the Investigator and affect the participant's suitability to participate in the study or put the participant at risk if he/she enters the study in the Investigator's opinion.
• Female participants who are pregnant, planning to become pregnant or breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 25 centers

• The University of Alabama at Birmingham — Birmingham
• University of California, San Diego — La Jolla
• UCLA Medical Center — Los Angeles
• UC Davis Medical Center — Sacramento
• Georgetown University — Washington D.C.
• University of Miami-U Health Boca Raton — Boca Raton
• University of Florida (Norman Fixel Institute for Neurological Diseases) — Gainesville
• Northwestern University — Chicago
• … and 17 more centers

Germany · 6 centers

• Universitaetsklinikum Aachen AöR — Aachen
• Katholisches Klinikum Bochum gGmbH — Bochum
• Universitätsklinikum Erlangen — Erlangen
• George-Huntington-Institut GmbH — Münster
• Isar Amper Klinikum — Taufkirchen
• Universitaetsklinikum Ulm AöR — Ulm

Italy · 6 centers

• Azienda Unita Sanitaria Locale Di Bologna — Bologna
• IRCCS Istituto Auxologico Italiano — Milan
• Azienda Ospedaliera Universitaria Federico II Di Napoli — Naples
• Azienda Ospedale Università di Padova — Padova
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma
• Casa Sollievo Della Sofferenza — San Giovanni Rotondo

Canada · 5 centers

• University of Calgary — Calgary
• University of Alberta — Edmonton
• University of British Columbia — Vancouver
• North York General Hospital — Toronto
• Centre Hospitalier de l'Universite de Montreal (CHUM) — Montreal

Spain · 5 centers

• Hospital Universitario De Cruces — Barakaldo
• Hospital De La Santa Creu I Sant Pau — Barcelona
• Hospital Universitario Ramon Y Cajal — Madrid
• Hospital Universitario Central De Asturias — Oviedo
• Hospital Universitario Virgen del Rocío — Seville

United Kingdom · 5 centers

• NHS Grampian — Aberdeen
• Birmingham and Solihull Mental Health Foundation NHS Trust — Birmingham
• Cardiff University — Cardiff
• The Walton Centre NHS Foundation Trust — Liverpool
• CNTW NHS Foundation Trust — Newcastle upon Tyne

France · 4 centers

• Centre Hospitalier Universitaire D'Angers — Angers
• CHU Henri Mondor (APHP) — Créteil
• Centre Hospitalier Universitaire Grenoble Alpes — La Tronche
• Centre Hospitalier Regional De Marseille — Marseille

Portugal · 4 centers

• Unidade Local De Saude De Coimbra E.P.E — Coimbra
• Unidade Local De Saude De Santa Maria E.P.E. — Lisbon
• Unidade Local De Saude De Santo Antonio E.P.E. — Porto
• CNS Saude Lda. — Torres Vedras

Belgium · 2 centers

• Hopital Erasme — Anderlecht
• Cliniques Universitaires Saint-Luc — Woluwe-Saint-Lambert

Poland · 2 centers

• Krakowska Akademia Neurologii Sp. z o.o. — Krakow
• Wojskowy Instytut Medycyny Lotniczej — Warsaw

Czechia · 1 center

• Vseobecna Fakultni Nemocnice V Praze — Prague

Netherlands · 1 center

• Leids Universitair Medisch Centrum (LUMC) — Leiden

Identifiers

NCT: NCT07609108 · PL101-HD302/ FNP253-CT-2502 · 2026-526093-16-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗