Proof-HD (Prilenia)


about the study

PROOF-HD is a global Phase 3, randomized, double-blind, placebo-controlled, parallel arm, multicenter study evaluating the efficacy and safety of pridopidine in patients with early stage HD.

Sponsor: Prilenia Therapeutics


about the experimental drug  

Pridopidine is a highly selective Sigma-1 receptor (S1R) agonist. It binds and activates the S1R, a protein that is expressed at high levels within the brain and regulates key cellular pathways, commonly impaired in neurodegeneration.

Pridopidine, by activation of the S1R, demonstrates beneficial effects in numerous cellular and animal models of HD. For example, pridopidine rescues neurons from mutant Huntingtin (mHTT) induced cell death, in HD patient-derived induced Pluripotent Stem Cells (iPSCs) and in mouse HD neurons. Furthermore, HD mice treated with pridopidine show improvement in multiple behavioral and motor functions. 


Patients will be treated with pridopidine, administered orally in the form of two capsules, twice daily. The study will evaluate its effect on functional capacity, as well as on motor and behavioral features in participants with early-stage HD. 

study sites

PROOF-HD will take place in U.S., Canada and Europe. The study will take place at approximately 60 study centers in North America and in the EU and it will enroll 480 participants. Read More 

treatment period

The double-blind treatment period will last 78 weeks.

The study will consist of a screening period, a double-blind treatment period (Main study) and an Open-label extension (OLE).

inclusion criteria 

Eligible participants should meet the following criteria:

  • Male or female, 25 years of age and older, capable of giving informed consent.
  • Have a diagnosis of HD based on clinical features.
  • Have confirmed presence of CAG repeats of 36 or greater in the huntingtin gene.
  • Must have adult-onset HD with onset of signs and symptoms at, or later than 18 years of age
  • Stable heath conditions within 12 weeks before baseline.


Questions and Answers 

We thank Prilenia's team for providing the answers to following questions we received from patients:


Is it true that pridopidine slows the progression of HD by 80%? 

The PRIDE-HD clinical trial evaluated the effect of pridopidine in HD patients up to 52 weeks. 

In an additional analysis, 81.1% of the early HD patients, treated with pridopidine at 45 mg bid showed no worsening in Total Functional Capacity (TFC) at 1 year. Worsening was defined as a drop of 1 point on TFC scale. TFC is a widely used and regulatory accepted scale, assessing disease stage and clinical progression.  In other words, we can say that pridopidine at the clinical dose (45 mg bid) showed an 80%  decrease in the chance of getting worse in function in patients with early HD. Pridopidine at 45 mg bid is the dose we are currently using in our PROOF-HD trial. 

Q: What effect does pridopidine have on movement disorders? 

Importantly, pridopidine was initially postulated to act via dopamine receptors and that its key benefit was on the motor system. However, subsequent studies have clearly shown that pridopidine works via the Sigma 1 Receptor (a protein highly expressed in the brain) and may have broad neuroprotective effects

Prior clinical trials in HD assessed the effect of pridopidine on motor function. In these trials, there was a significant benefit of pridopidine 45 mg bid on the Total Motor Score (TMS), compared to placebo (TMS was a secondary endpoint).  In addition, more objective motor assessments (using a test battery that objectively measures movement; Q-motor) have supported the motor improvements observed in these trials,  in the 1-year PRIDE-HD trial.  

In the ongoing PROOF-HD study, motor aspects are being assessed as part of the secondary endpoints and include both TMS and Q-motor evaluations. 

The above findings were observed in clinical trials. Currently, the compound is not approved anywhere.


Learn More 

Click here to read the FAQ on the Prilenia website