PRidopidine Phase 3 Study to Establish Clinical Impact and Safety in Huntington's Disease (PRECISE-HD)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: Pridopidine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Prilenia Medical Information Executive Director Clinical Operations; Phone Number: 018575745755; Email: MedInfo@prilenia.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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
Experimental: Pridopidine; During the titration period (2 weeks), pridopidine 45 mg capsules will be taken orally once daily (in the morning) for 2 weeks. Afterwards, pridopidine 45 mg capsules will be taken orally twice daily (in the morning and in the afternoon; 7-10 hours apart) for 50 weeks.	Drug: Pridopidine; Pridopidine hard gelatin capsule
Placebo Comparator: Placebo; During the titration period (2 weeks), matched placebo hard gelatin capsules will be taken once daily (in the morning) for 2 weeks. Afterwards, placebo capsules will be taken twice daily (in the morning and in the afternoon; 7-10 hours apart) for 50 weeks.	Drug: Placebo; Matched placebo hard gelatin capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Composite Unified Huntington's Disease Rating Scale (cUHDRS)	cUHDRS is a combined score to assess disease progression in HD. It includes TFC, TMS, SDMT, and SWR: 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 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. Participant 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 integrated cUHDRS scale range: -7.6 to 24.8. The higher, the better.	Change from Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Functional Capacity (TFC) score	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.	Change from Baseline to Week 52
Change in Quantitative Motor (Q-Motor) Finger Tapping Inter-Onset Interval (FT-IOI) mean	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. Higher score = worse outcome.	Change from Baseline to Week 52
Change in Stroop Word Reading (SWR) score	Stroop Word Reading (SWR) measures attention and mental flexibility. Participant reads names of colors printed in black ink. Scores reflect correct responses in 45 sec. Higher score = better outcome.	Change from Baseline to Week 52

Collaborators and Investigators

• Sponsor: Prilenia
• Collaborators: Ferrer Internacional S.A.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• 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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Huntington Disease; pridopidine
• Other Study ID Numbers: PL101-HD302/ FNP253-CT-2502; 2026-526093-16-00 (Ctis)

Drug and device information, study documents

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