First participant dosed in the PRECISE-HD trial of pridopidine
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A global Phase 3 clinical trial, PRECISE-HD, has begun dosing participants to evaluate the efficacy of the investigational drug pridopidine in slowing disease progression for Huntington’s disease patients.
A new Huntington’s disease (HD) clinical trial has officially begun, marking another important step in the search for treatments that could slow the progression of the disease. Prilenia Therapeutics and Ferrer have announced via a Linkedin post that the first participant has been dosed in the PRECISE-HD Phase 3 clinical trial, which is testing the investigational drug pridopidine.
Another chance for pridopidine
Long-time HDBuzz HDBuzz readers may recognise pridopidine. Pridopidine has had one of the longest and most winding development journeys of any experimental HD therapy. Originally developed as a treatment for movement symptoms, early clinical trials failed to meet their primary goals despite nuanced hints of benefit on some tests.
In 2023, the large Phase 3 PROOF-HD study did not meet its primary goal of slowing disease progression across all participants. However, a planned analysis of the data suggested that people who were not taking antidopaminergic medications (ADMs) appeared to have greater benefit from pridopidine than those who were taking these medications. ADMs are drugs commonly prescribed to treat chorea or psychiatric symptoms.
Those findings prompted discussions with regulators and the HD community about how best to determine whether this apparent benefit was real. What emerged is PRECISE-HD: a new confirmatory trial specifically designed to test that hypothesis.
What is PRECISE-HD?
PRECISE-HD is a global Phase 3 study that plans to enroll approximately 400 people aged 23-65 with early- to mid-stage HD across up to 75 clinical sites in North America and Europe.
Participants will be randomly assigned to receive either pridopidine or placebo, in two groups. For the first two weeks they will take one capsule by mouth every morning, then morning and afternoon, for one year. Over the course of the year, participants will visit the clinic 6 times, and they will have 5 safety checks over the phone. This is a double-blind study, meaning neither participants nor researchers know who is receiving which treatment during that period. Those who complete this stage will then have the opportunity to continue into a two-year study known as an open-label extension, where everyone receives pridopidine.
To better evaluate the subgroup that previously appeared to benefit, the study will enroll people who have not recently been treated with antidopaminergic medications.
Researchers will measure whether pridopidine affects several aspects of HD, including overall disease progression (using the composite Unified Huntington’s Disease Rating Scale, or cUHDRS), day-to-day functioning, movement symptoms, thinking and cognition, speech and quality of life.
How might pridopidine work?
Unlike huntingtin-lowering therapies, pridopidine does not target the huntingtin gene or protein directly. Instead, it targets a protein called the sigma-1 receptor, which is thought to help nerve cells cope with stress and to support several pathways involved in maintaining healthy brain function. Laboratory studies suggest this signalling may promote nerve cell survival and resilience, although whether this translates into slowing HD progression in people remains to be proven.
