Huntington DiseasePhase 3NCT04556656

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

A Phase 3 study testing Pridopidine in people with Huntington Disease, run by Prilenia at 58 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 25 years and older
Conditions the study is for: Huntington Disease
What is being tested?: Pridopidine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 499 participants
Where: 58 sitesin 11 countries
Study dates: 16 Oct 2020to 21 Mar 2024
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

58 sites in 11 countries.

Country

City, postcode or hospital

58 sites in 11 countries

United States26 sites

Prilenia Investigational Site (Site 037)
Albany, New York, 12208
Prilenia Investigational Site (Site 032)
Atlanta, Georgia, 30322
Prilenia Investigational Site (Site 028)
Baltimore, Maryland, 21218
Prilenia Investigational Site (Site 017)
Boston, Massachusetts, 02114
Prilenia Investigational Site (Site 076)
Boston, Massachusetts, 02215
Prilenia Investigational Site (Site 088)
Chicago, Illinois, 60611
Prilenia Investigational Site (Site 089)
Cincinnati, Ohio, 45221
Prilenia Investigational Site (Site 020)
Columbus, Ohio, 43210
Prilenia Investigational Site (Site 061)
Davis, California, 95616
Prilenia Investigational Site (Site 119)
Durham, North Carolina, 27708
Prilenia Investigational Site (Site 343)
Englewood, Colorado, 80113
Prilenia Investigational Site (Site 160)
Gainesville, Florida, 32611
Prilenia Investigational Site (Site 199)
Houston, Texas, 77004
Prilenia Investigational Site (Site 029)
Kansas City, Kansas, 66103
Prilenia Investigational Site (Site 087)
Louisville, Kentucky, 40292
Prilenia Investigational Site (Site 031)
Nashville, Tennessee, 37232
Prilenia Investigational Site (Site 002)
New York, New York, 10027
Prilenia Investigational Site (Site 018)
Philadelphia, Pennsylvania, 19104
Prilenia Investigational Site (Site 006)
Portland, Oregon, 97239
Prilenia Investigational Site (Site 326)
Richmond, Virginia, 23284
Prilenia Investigational Site (Site 051)
San Diego, California, 92093
Prilenia Investigational Site (Site 096)
Seattle, Washington, 98195
Prilenia Investigational Site (Site 027)
St Louis, Missouri, 63130
Prilenia Investigational Site (Site 019)
Tampa, Florida, 33620
Prilenia Investigational Site (Site 333)
Washington D.C., District of Columbia, 20057
Prilenia Investigational Site (Site 083)
Wichita, Kansas, 67226

Other trials in United States

Germany6 sites

Prilenia Investigational Site (Site 234)
Aachen
Prilenia Investigational Site (Site 379)
Bochum
Prilenia Investigational Site (Site 377)
Lübeck
Prilenia Investigational Site (Site 376)
Münster
Prilenia Investigational site (Site 292)
Taufkirchen
Prilenia Investigational Site (Site 175)
Ulm

Other trials in Germany

Italy5 sites

Prilenia Investigational Site (Site 249)
Bari
Prilenia Investigational Site (Site 394)
Bologna
Prilenia Investigational Site (Site 239)
Milan
Prilenia Investigational Site (Site 393)
Naples
Prilenia Investigational Site (Site 228)
Roma

Other trials in Italy

Canada4 sites

Prilenia Investigational Site (Site 030)
Calgary, Alberta, AB T2N 1N4
Prilenia Investigational Site (Site 232)
Halifax, NS B3S 1L8
Prilenia Investigational Site (Site 098)
Montreal, Quebec, QC H2X 3E4
Prilenia Investigational Site (Site 048)
Vancouver, British Columbia, BC V6T 1Z4

Other trials in Canada

Spain4 sites

Prilenia Investigational Site (Site 380)
Barcelona
Prilenia Investigational Site (Site 381)
Burgos
Prilenia Investigational Site (Site 176)
Madrid
Prilenia Investigational Site (Site 382)
Valencia

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France3 sites

Prilenia Investigational Site (Site 385)
Lille
Prilenia Investigational Site (Site 384)
Marseille
Prilenia Investigational Site (Site 392)
Paris

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Poland3 sites

Prilenia Investigational Site (Site 386)
Gdansk
Prilenia Investigational Site (Site 244)
Krakow
Prilenia Investigational Site (Site 246)
Warsaw

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United Kingdom3 sites

Prilenia Investigational Site (Site 180)
Aberdeen
Prilenia Investigational Site (Site 390)
Cardiff
Prilenia Investigational Site (Site 378)
Newcastle

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Netherlands2 sites

Prilenia Investigational Site (Site 044)
Leiden
Prilenia Investigational Site (Site 387)
Maastricht

Other trials in Netherlands

Austria1 site

Prilenia Investigational site (Site 291)
Innsbruck

Other trials in Austria

Czechia1 site

Prilenia Investigational Site (Site 388)
Prague

Other trials in Czechia

About this study

Official 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

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

Read the 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.

Conditions: Huntington Disease
Being tested: Pridopidine, Placebo
Keywords: Huntington Disease
Medical subject headings: Huntington Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PridopidineDrug
Pridopidine hard gelatin capsule
PlaceboDrug
Pridopidine-matching placebo hard gelatin capsule

Study groups in NCT04556656
Study group	Role	What they receive
Pridopidine	Experimental	45 mg pridopidine twice daily (BID) Receives: Drug: Pridopidine
Placebo	Placebo comparator	Matching placebo Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: From baseline to Week 65.

Secondary outcomes (1)

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.
Measured: From baseline to Week 65

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Oct 202021 Mar 2024

First posted21 Sep 2020
Study start16 Oct 2020
Primary completion14 Mar 2023
Study completion21 Mar 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Huntington DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 499 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04556656
Sponsor's protocol ID: PL101-HD301
Other IDs: 2020-002822-10
Status last verified: Feb 2025
First submitted: 14 Sep 2020
Last updated: 12 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Anderson KE, Tan AM, Feigin A, Reilmann R, Rosser AE, Raymond LA, Kostyk SK, Saft C, Chen K, Hand R, Geva M, Hayden MR; PROOF-HD study investigators. Antidopaminergic Medications and Clinical Outcomes in Huntington Disease: Evidence From the PROOF-HD Placebo-Controlled Trial. Neurology. 2026 Nov 24;107(10):e218627. doi: 10.1212/WNL.0000000000218627. Epub 2026 Oct 22.
PubMed 42912861
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.
PubMed 40913168

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Huntington Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official 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
ClinicalTrials.gov ID: NCT04556656
Acronym / sponsor ID: PL101-HD301
Conditions: Huntington Disease
Keywords: Huntington Disease
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 499 participants (actual)
Lead sponsor: PrileniaIndustry (pharma, biotech, devices)
Study start: 16 Oct 2020 (actual)
Primary completion: 14 Mar 2023 (actual)
Study completion: 21 Mar 2024 (actual)
First posted: 21 Sep 2020 (actual)
Results: Posted 12 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Pridopidine	Experimental	Drug: Pridopidine45 mg pridopidine twice daily (BID)
Placebo	Placebo comparator	Drug: PlaceboMatching placebo

Who may qualify

Ages: 25 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PridopidinePridopidine hard gelatin capsule	Drug	Pridopidine
PlaceboPridopidine-matching placebo hard gelatin capsule	Drug	Placebo

Primary outcome

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.
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.

1 secondary outcome

Change From Baseline to Week 65 in Composite UHDRS (cUHDRS) Total Score (mITT)
Time frame: From baseline to Week 65

Results and safety

Results posted to the registry on 12 Mar 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pridopidine	250	222
Placebo	249	227

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

Time frame: From baseline to Week 65. Least squares mean (Standard Error). Unit: score on a scale

Measure	Pridopidine n = 243	Placebo n = 247
Value	-1.18 (0.119)	-0.95 (0.119)

Pridopidine vs Placebo: Mean Difference (Final Values): -0.22 (95% CI -0.54 to 0.09), p = 0.1670, Mixed Models Analysis

Population analysed: The modified intent to treat (mITT) population included all participants in the ITT population who received at least one dose of study drug and had valid in clinic TFC scores both at baseline and at least one post-baseline timepoint. The mITT population was analyzed according to the treatment to which the participant was randomized. The mITT population was the main analysis population for the primary endpoint in non-EMA regions. Note that the analysis was based on observed data.

Primary outcome: Change From Baseline to Week 65 in the UHDRS TFC Score (ITT)

Time frame: From baseline to Week 65.. Least squares mean (Standard Error). Unit: score on a scale

Measure	Pridopidine n = 250	Placebo n = 249
Value	-1.17 (0.120)	-0.94 (0.120)

Pridopidine vs Placebo: Mean Difference (Final Values): -0.23 (95% CI -0.55 to 0.09), p = 0.1598, Mixed Models Analysis

Population analysed: The intent to treat (ITT) population included all randomized participants. The ITT population was analyzed according to the treatment to which the participant was randomized. The ITT population was the main analysis population for the primary endpoint in the EMA region.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From Screening until 2 weeks after End of Study/End of Treatment visit (total treatment period of up to 78 weeks).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pridopidine	34 of 250 (13.6%)	204 of 250 (81.6%)	4 of 250
Placebo	21 of 249 (8.4%)	212 of 249 (85.1%)	1 of 249

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42912861Anderson KE, Tan AM, Feigin A, Reilmann R, Rosser AE, Raymond LA, Kostyk SK, Saft C, Chen K, Hand R, Geva M, Hayden MR; PROOF-HD study investigators. Antidopaminergic Medications and Clinical Outcomes in Huntington Disease: Evidence From the PROOF-HD Placebo-Controlled Trial. Neurology. 2026 Nov 24;107(10):e218627. doi: 10.1212/WNL.0000000000218627. Epub 2026 Oct 22.
Derived from this study: PubMed 40913168Reilmann 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Yael Cohen study director

Prilenia

58 sites in 11 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pridopidine in people with Huntington Disease, run by Prilenia at 58 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in United States, Germany, Italy, Canada, Spain and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04556656, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2025.