1st patient dosed in Phase 2 trial of oral CVN424 for early Parkinson’s

ASCEND trial still recruiting participants at 2 sites in Arizona and Michigan

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by Andrea Lobo |

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Cerevance has dosed the first participant in a Phase 2 clinical trial evaluating the safety and efficacy of its investigational oral therapy CVN424 for Parkinson’s disease.

The ASCEND trial (NCT06006247) will explore the safety and efficacy of CVN424 as a single therapy in people with early-stage Parkinson’s disease, who have not yet started on standard Parkinson’s treatments.

The trial is still recruiting patients at two sites in the U.S. in Scottsdale, Arizona, and Farmington Hills, Michigan.

“We are delighted to announce the commencement of our ASCEND study in individuals who have recently been diagnosed with Parkinson’s disease and not yet received levodopa treatment,” Craig Thompson, Cerevance’s CEO, said in a company press release.

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Fewer side effects expected with CVN424 than with standard treatments

Parkinson’s is caused by the dysfunction and death of dopamine-producing neurons in a brain region called the substantia nigra, causing a deficit of dopamine in the striatum, which is a brain region involved in motor control. Dopamine is a major brain chemical messenger.

Standard treatments for Parkinson’s include levodopa and its derivatives, which are designed to increase dopamine signaling in the brain.

CVN424 does not act on dopamine signaling. Instead, the small molecule can penetrate the brain and block GPR6, a protein receptor produced by a specific type of neuron in the striatum that plays a role in helping to regulate and control movements.

By suppressing GPR6, CVN424 is expected to normalize the activity of these neurons, resulting in positive effects similar to the current standard of care, while avoiding the adverse events associated with dopamine-based therapies, such as dyskinesia (uncontrolled and involuntary movements).

A Phase 1 study (NCT03657030) in healthy volunteers showed CVN424 was safe and well tolerated. The therapy was found to be rapidly absorbed, and its stability profile supported a once-daily dose as the optimal treatment regimen for further studies.

Additionally, a previous Phase 2 clinical trial (NCT04191577) testing CVN424 in adults with Parkinson’s who were on levodopa, showed promise in easing the disease’s non-motor and motor symptoms. The therapy significantly reduced “off” time by more than one hour per day compared to a placebo. Off time occurs when the medication wears off and symptoms return before it is time for the next dose.

The results from this trial also indicated CVN424 enhanced levodopa’s effects without dyskinesia and reduced daytime sleepiness.

The ASCEND Phase 2 trial expects to enroll 60 people, 30 and older, with early untreated Parkinson’s, who will be randomized to receive a once-daily 150 mg dose of CVN424 or a placebo.

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Study seeks to test efficacy of CVN424 in easing symptoms

The study’s main goal is to evaluate the therapy’s efficacy in easing Parkinson’s motor symptoms. It will also address the impact of the treatment on non-motor symptoms and activities of daily living, for up to 12 weeks (or three months) of treatment.

“This study aims to build upon the promising results from our previous Phase 2 trial of CVN424 as an adjunctive therapy for later-stage Parkinson’s disease,” Thompson said. “Our objective is to demonstrate the advantages of CVN424 over existing treatments in improving both the motor and non-motor symptoms of Parkinson’s disease. With ASCEND, we take a significant step closer to providing patients with an innovative, safe, and well-tolerated treatment that addresses multiple facets of this disease.”

Findings from this trial will support the design of a Phase 3 trial to test the efficacy of CVN424 in delaying disease progression, and the need for levodopa, in people with early-stage Parkinson’s disease.