Efficacy and Safety of CVN424 in Reducing Motor Complications in Parkinson's Disease: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Multicenter Trial
- Trial ID
- 2024-516811-25-00
- Protocol
- CVN424-301
- Sponsor
- Cerevance Beta Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2, randomized, double-blind, placebo-controlled multicenter study is to assess the **efficacy** of CVN424, administered once daily, in reducing **OFF time** in patients with Parkinson's Disease. This is clinically relevant as reducing OFF time can significantly improve the quality of life for patients by enhancing their motor function and daily activities.
Secondary objectives include:
- Evaluating ON time without troublesome dyskinesia, which is the sum of ON time without dyskinesia and ON time with non-troublesome dyskinesia.
- Further assessment of CVN424's motor effects in Parkinson's Disease, including a complete motor diary profile and MDS-UPDRS scores.
- Measuring CVN424's effects on non-motor features, function, global assessments, and quality of life in Parkinson's Disease.
- Collecting safety and tolerability data for CVN424 in Parkinson's Disease.
Participants
The clinical trial involves a total of **205 participants** diagnosed with **Parkinson's Disease**. The study population includes both male and female subjects, aged 30 years and older, who meet specific health criteria. Participants are required to have a **Body Mass Index (BMI)** between 18.0 and 35.0 kg/m² and must be freely ambulatory, with or without an assistive device, at the time of screening. The trial population was selected based on their ability to identify ON, OFF, and dyskinetic states with high concordance through completed diaries. Participants must have stable Parkinson's Disease medications for a specified period before screening and demonstrate a prominent response to levodopa. The study also considers lifestyle factors, such as the stability of oral anti-sialorrhea medications and the frequency of levodopa administration. Both genders are included, and the trial involves a vulnerable population, ensuring comprehensive representation. Participants must agree to use reliable contraception if applicable and provide informed consent to comply with study procedures.
Plans and Procedures
The clinical trial is a **Phase 2**, randomized, double-blind, placebo-controlled multicenter study designed to evaluate the efficacy of CVN424 in patients with **Parkinson's Disease** who experience motor complications. The primary objective is to assess the change in OFF time when CVN424 is administered once daily compared to a placebo. The trial is expected to last approximately 12 weeks, with participant involvement spanning the same duration. The study will commence with a screening visit to confirm eligibility based on criteria such as age, diagnosis, and medication stability. Participants must be at least 30 years old, have a diagnosis consistent with UK Brain Bank criteria, and demonstrate a stable medication regimen prior to screening.
Following the screening, eligible participants will be randomized to receive either CVN424 or a placebo. The trial will include several follow-up visits to monitor efficacy and safety, with assessments conducted through motor diaries and various questionnaires. The primary endpoint is the change in average daily OFF time from baseline to week 12. Secondary endpoints include safety assessments and changes in clinical scales. The end-of-study visit will conclude the trial, where final evaluations will be conducted.
Participants are expected to adhere to the study protocol, including scheduled visits and medication regimens. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation. The trial aims to provide valuable insights into the potential benefits of CVN424 for managing motor complications in Parkinson's Disease.
Treatment
The clinical trial involves the administration of **CVN424**, an experimental medication formulated as a **tablet**. The active substance in CVN424 is chemically synthesized and identified as 1-[2-[4-(2,4-difluorophenoxy)piperidin-1-yl]-3-[[(3R)-oxolan-3-yl]amino]-7,8-dihydro-5H-pyrido[3,4-b]pyrazin-6-yl]ethanone. This compound is administered orally. Two dosage regimens are being evaluated: a maximum daily dose of 150 mg and a lower dose of 75 mg. The total maximum dose over the treatment period is 12,600 mg for the higher dose and 6,300 mg for the lower dose. The treatment period extends up to 12 weeks. The medication is not formulated for pediatric use and is not classified as an orphan drug.
In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind study. The placebo is also administered in the form of film-coated tablets for oral administration. The placebo is designed to match the experimental medication in appearance to maintain blinding. The placebo does not contain the active substance and serves as a control to assess the efficacy of CVN424 in reducing OFF time in patients with Parkinson's Disease.
Efficacy
The efficacy of the investigational product CVN424 in the treatment of **Parkinson's Disease** with motor complications will be assessed through a Phase 2, randomized, double-blind, placebo-controlled multicenter study. The primary endpoint for evaluating efficacy is the change from baseline to Week 12 in average daily OFF time, as recorded on motor diaries, for patients receiving 150 mg of CVN424 compared to those receiving a placebo. This measurement will be normalized to waking hours to ensure consistency and accuracy in the assessment.
Secondary endpoints include the change from baseline to the end of the study treatment at Week 12, compared to placebo, as assessed through various questionnaires and scales utilized during the study. Additionally, safety will be evaluated by monitoring the number of patients reporting treatment-emergent adverse events and serious adverse events, as well as any clinically significant changes in physical examinations, vital signs, 12-lead ECG, and laboratory data. These assessments will provide a comprehensive evaluation of the efficacy and safety profile of CVN424 in the target patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- At least 30 years of age at the time of Screening.
- Diagnosis of Parkinson’s Disease (PD) consistent with UK Brain Bank criteria and MDS Research Criteria for the Diagnosis of PD; must include bradykinesia with sequence effect and motor asymmetry if no rest tremor, and a prominent response to levodopa.
- BMI > 18.0 and < 35.0 kg/m2, inclusive at Screening.
- Modified Hoehn and Yahr Stage ≤ 3 in the ON state.
- Freely ambulatory at the time of Screening (with/without assistive device).
- Montreal Cognitive Assessment (MoCA) Score of at least 24.
- PD medications must be stable for at least 4 weeks prior to Screening; MAO-B inhibitors must be stable for at least 12 weeks prior to Screening.
- Levodopa administration at least 4 times daily (immediate or extended release) or three times daily (Rytary or Crexont).
- Stable use of oral anti-sialorrhea medications for 30 days before Screening, without anticipated need for change during the study.
- Average of ≥ 3 h total OFF time/day on Screening home diaries, with at least 2.5 hours OFF on each diary day.
- During Screening, capable of adequately identifying ON, OFF, and dyskinetic states (>80% concordance) through properly completed ON/OFF diaries.
- Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and for at least 12 weeks after the last dose of study drug has been taken.
- Able and willing to give written informed consent approved by an institutional review board, and to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.
- Approved as an appropriate and suitable candidate by the Enrollment Authorization Committee (EAC).
Exclusion Criteria
- Diagnosis of secondary or atypical parkinsonism.
- Current use of medication with dopamine antagonist activity, or any use within 12 months of Screening.
- Clinically significant medical, surgical, psychiatric, or laboratory abnormalities that in the judgment of the investigator would preclude adequate participation or completion of the study.
- Clinically significant ECG abnormalities at Screening.
- Prolonged Fridericia-corrected QT (QTcF) interval on ECG at Screening.
- 14.Clinically significant heart disease within 2 years of Screening, defined as follows: •Significant cardiac event within 12 weeks prior to Screening (e.g., admission for myocardial infarction, unstable angina, or decompensated heart failure), angina pectoris or episode of congestive heart failure with symptoms > grade 2 New York Heart Association classification, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia. •History of complex arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment. •Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. •Symptomatic bradycardia, sick sinus syndrome or atrioventricular block greater than first degree in the absence of a pacemaker. •Unexplained syncope. •Brugada syndrome. •Hypertrophic cardiomyopathy.
- Any clinically significant history of malignancy or ongoing malignancy of sufficient concern for interference with completion of the study or quality of study experience, in the opinion of the investigator and medical monitor.
- Active major depressive disorder or a Beck Depression Inventory-II (BDI-II)score of > 19.
- Has active suicidal ideation within one year prior to Screening as determined by the C-SSRS or attempted suicide within the last 5 years.
- Has been diagnosed with or history of a substance-related disorder (excluding nicotine and caffeine), including alcohol-related disorder by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria, during the 12 months prior to Screening.
- Tests positive at Screening for drugs of abuse. Drugs of abuse refers to illicit substances and does not include patients taking physician-prescribed medications. For participants who are legally prescribed cannabis for medical reasons, the appropriateness of the participant for this study will be made by the judgement of the Investigator in consultation with the Medical monitor.
- Severe or disabling dyskinesias or OFF expected to preclude successful study participation, in the opinion of the investigator.
- Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN) or a degree of hepatic impairment using the Child-Pugh classification of B or C.
- Significant renal impairment as determined by estimated glomerular filtration rate (eGFR) less than or equal to 60 ml/min.
- Has a positive test result for HBsAg, HCV antibody, or HIV infection at Screening.
- Currently lactating or pregnant or planning to become pregnant during the study.
- Previous exposure to CVN424.
- Currently participating in or has participated in another study of an IMP or medical device in the last 3 months or within 5 half-lives of the IMP (whichever is longer) prior to Screening.
- Any previous procedure or therapy designed to provide continuous levodopa or stimulation of dopaminergic tone (i.e., Duopa, apomorphine, subcutaneous levodopa), surgery for PD (i.e., deep brain stimulation [DBS]), or anticipation of these during the study.
- History of exclusively diphasic, OFF state, myoclonic or dystonic dyskinesias without peak-dose choreiform dyskinesia.
- Clinically significant orthostatic hypotension (consistently symptomatic or requires medication).
- Clinically significant hallucinations requiring antipsychotic use.
- Current use of strong CYP3A4/5 inhibitors or inducers.
- Routine use of PD on-demand medications (i.e., inhaled levodopa, apomorphine injection). Routine use defined three (3) or more uses per week of on-demand medication is not allowed.
- Use of injectable botulinum medication for sialorrhea within 90 days of screening or during the study.
- A known hypersensitivity to the IMP or to any excipients used in the formulation.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 31 Mar 2025 | 29 |
 France | Not Recruiting | 31 Mar 2025 | 25 |
 Italy | Not Recruiting | 31 Mar 2025 | 21 |
 Poland | Not Recruiting | 31 Mar 2025 | 41 |
 Spain | Not Recruiting | 31 Mar 2025 | 32 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
CVN424 | Test | TABLET | ORAL | 75.00 | 12 | PRD11610498 |
CVN424 | Test | TABLET | ORAL | 150.00 | 12 | PRD11610499 |
film-coated tablets for oral administration | Placebo | N/A | — | — | — | N/A |