The trial will feature 60 individuals with early-stage Parkinson disease who will be randomly assigned 1:1 to either daily CVN424 or placebo for a 12-week treatment period.
According to an announcement, dosing is underway for the phase 2 ASCEND study (NCT06006247) assessing Cerevance’s investigational agent CVN424 in patients with early-stage untreated Parkinson disease (PD).1
CVN424, a first-in-class non-dopamine therapy that selectively modulates GPR6, an orphan G-protein coupled receptor, will be evaluated in a cohort of 60 patients. The study’s primary end point will be change in Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale parts II and III, measures of motor symptoms and activities of daily living, over a 12-week period. Notably, the study will also incorporate several digital health technologies to objectively evaluate disease progression or lack of disease progression.
"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, chief executive officer at Cerevance, said in a statement.1 "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. 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."
In the study, patients with untreated PD aged 30 years and older who have not received levodopa therapy will be randomly assigned 1:1 to either once daily dose of CVN424 150 mg or placebo. Patients must have a modified Hoehn and Yahr score of less than 2.5 at screening, a Montreal Cognitive Assessment score of at least 26, and are freely ambulatory upon entry. A diagnosis secondary or atypical parkinsonism, previously surgical procedure for PD, or treatment with dopamine agonist or monoamine oxidase-B inhibitors are all within the exclusions of the study.
"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,” Thompson added.
In March 2022, the company announced positive data from a phase 2 study (NCT04191577) assessing the agent in a cohort of 135 patients with PD. Coming into the study, patients were on a stable dosage of levodopa and other PD medications but had at least 2 hours or more of average daily OFF time. Over a 4-week treatment period, high-dose CVN424 improved OFF time by 1.3 hours compared with placebo (P = .042). CVN424 also demonstrated an encouraging adverse event (AE) profile, with nausea, vomiting, and headache, each occurring in 4% of individuals in the high-dose group, as the most reported AEs.2
In the low-dose arm, initiation of treatment occurred on day 1, with continued low-dose each day, while the high-dose arm increased their daily dosage to the high-dose level beginning on day 8 and continued thereafter. In addition to improvements in OFF time, the high-dose group showed an increase in ON time without troublesome dyskinesia and continued to show improved efficacy as the study went along. At 4 weeks vs at 2 weeks, daytime sleepiness as measured by the Epworth Sleepiness Scale, was reduced compared with placebo. The low-dose group also showed meaningful improvements in OFF time and ON time without troublesome dyskinesia compared to those on placebo.