CVN424 is small molecule that can penetrate the brain and modulate the activity of specific nerve cells in the striatum region that control body movement. In contrast to available therapies, CVN424 specifically targets a non-dopaminergic protein involved in signaling pathways that can activate brain cells.
This new strategy is anticipated to induce positive therapeutic effects similar to current standard-care treatments for Parkinson’s while avoiding side effects such as dyskinesia.
“We are pleased to further advance the clinical development of CVN424 in Parkinson’s, as there remain significant shortcomings with current therapeutics,” Brad Margus, Cerevance’s CEO, said in a press release.
Preclinical studies have shown that CVN424 can improve locomotor activity in animal models of Parkinson’s disease.
Results from a previous Phase 1 study (NCT03657030) showed that CVN424 was safe and well-tolerated compared with placebo. The trial enrolled 64 healthy volunteers who received either single doses or seven daily doses of CVN424, ranging from 1 mg to 225 mg, or placebo. No serious or severe adverse events or clinically significant changes were reported or associated with the therapy.
Oral administration of CVN424 was rapidly absorbed by the body and its stability profile supported a once-daily dosing regimen as the optimal treatment approach for future studies.
These positive data supported the launch of the multicenter, placebo-controlled Phase 2 trial that will now evaluate CVN424’s efficacy and safety in Parkinson’s patients with motor fluctuations who are being treated with levodopa.
The trial is expected to enroll approximately 70 participants, ages 30 to 80, who will be randomly assigned to receive one of two doses of CVN424 or a placebo.
The researchers will evaluate CVN424’s potential for reducing “off” time — periods of the day when Parkinson’s symptoms return despite ongoing medication — as well as other functional outcome measures.
“CVN424 activates key motor pathways, but not the neurons implicated in dyskinesias, a common side effect of dopaminergic Parkinson’s disease treatments,” said David H. Margolin, MD, PhD, senior vice president of clinical and translational medicine at Cerevance. “This selectivity should allow CVN424 to augment the positive effects of the current standard of care, levodopa, without exacerbating its side effects.”
More information about the trial, including participating clinical sites and contacts, is available here.