ClinicalTrials.gov ID: NCT06006247
Ages Eligible: 30 Years and Older
Sexes Eligible: All
Study Phase: Phase 2
Study Completion (Estimated): 2025-02
Principal Investigator: Daniel J. Burdick, MD
Contact Information:
EvergreenHealth Research Department
425-899-5385
EvergreenResearch@evergreenhealthcare.org
Summary:
This is a multicenter, 12-week, placebo-controlled clinical trial of CVN424 150 milligrams (mg) tablets in early, untreated Parkinson's Disease (PD). Participants will be randomized in a 1:1 ratio to CVN424 150 mg or placebo at the Baseline Visit. The purpose of this study is to measure effect on motor features with CVN424 tablets compared to placebo in early, untreated PD and to evaluate the potential of CVN424 to improve motor and non-motor functions in participants with early PD who are not taking dopaminergic or anti-PD therapies.
Eligibility Criteria:
Inclusion Criteria
- Diagnosis of PD consistent with United Kingdom Brain Bank and Movement Disorder Society Research Criteria for the Diagnosis of PD; must include bradykinesia with sequence effect, and motor asymmetry if no PD-type rest tremor.
- Not receiving anti-parkinsonian therapy, and not expecting to require it for the duration of the study.
- Men or women of all races who are at least 30 years at Screening.
- Modified Hoehn and Yahr ≤ 2.5 at Screening.
- Montreal Cognitive Assessment (MoCA) ≥ 26.
- Freely ambulatory at time of Screening (with/without assistive device).
- 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 at least 30 days after the last dose of study drug has been taken.
- Able and willing to give written (signed and dated) informed consent approved by an institutional review board, and to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study.
- Approved as an appropriate and suitable candidate by the Enrollment Authorization Committee (EAC).
Exclusion Criteria
- Diagnosis of secondary or atypical parkinsonism.
- Diagnosis of parkinsonian motor signs or symptoms ≥ 4 years before Screening Visit.
- Previous surgical procedure for PD.
- Prior treatment with a dopamine agonist, levodopa, monoamine oxidase B (MAOB) inhibitor, or adenosine A2A receptor antagonists for more than 28 total days prior to screening. Additional exclusionary parameters around PD treatment include:
- Treatment with a dopamine agonist within 14 days of Screening.
- Treatment with a MAOB inhibitor within 90 days of Screening.
- Current use of any antipsychotic, metoclopramide, or reserpine. If previously used, this may not have been within 28 days of Screening or 5 elimination half-lives (whichever one is longer).
- Current use of potent Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers.
- Clinically significant orthostatic hypotension.
- Clinically significant hallucinations requiring antipsychotic use.
- Known autoimmune, malignancy (except basal cell carcinoma) or hematologic disease (prior or current) likely to interfere with the safe participation of the participant or interfere with assessment of safety or efficacy based on the opinion of the investigator and the medical monitor.
- Any clinically significant medical, surgical, or psychiatric abnormality that, in the judgment of the Investigator, is likely to interfere with study compliance, the safe participation of the participant or the assessment of safety or efficacy.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2 times the upper limit of normal (ULN), and total bilirubin greater than 1.5 times ULN.
- Participants with Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided that direct bilirubin is ≤ 1.5 times ULN.
- Significant renal impairment as determined by estimated glomerular filtration rate (eGFR) using creatinine clearance (CrCL) as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≤ 50 milliliters per minutes (mL/min).
- Participant has an ECG or clinical evidence of potentially unstable heart disease, including the following:
- QT interval corrected using Fridericia's formula (QTcF) > 470 milliseconds (msec) for female participants; > 450 msec for male participants
- Complete right or left bundle branch block
- History or clinical evidence of coronary artery disease, ischemic cardiac disease or myocardial infarct
- Clinically significant atrial or ventricular dysrhythmia; the heart must be in predominantly normal sinus rhythm
- Second- or third-degree atrioventricular (AV) block
- History or clinical evidence of heart failure
- History or clinical evidence of cardiomyopathy or cardiac structural abnormality
- Any other cardiac condition that the Investigator feels may predispose the participant to ischemia or arrhythmia
- Current (or within past 12 months) diagnosis or history of substance abuse (excluding nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders 5 criteria.
- Positive urine drug screen for tetrahydrocannabinol or any drugs that may affect participant safety or interfere with efficacy assessments.
- Medical or recreational use of marijuana within 2 months of the Screening Visit. Use of cannabidiol (CBD) is prohibited after the Screening Visit and throughout the study.
- Currently active major depression as determined by Beck Depression Inventory (BDI)-II score of > 19.
- Active suicidal ideation within 1 year prior to Screening Visit as determined by a positive response to Question 4 or 5 on the C-SSRS.
- Currently lactating or pregnant, or planning to become pregnant during the study.
- Current participation in another investigational clinical study and/or receipt of any investigational drug within 90 days prior to Screening.
- Prior use of CVN424 investigational product.
- Positive test for coronavirus disease 2019 (COVID-19). Confirmatory test will be allowed at the discretion of the Investigator to rule out false positives. A participant who tests positive for COVID-19 will be eligible to be rescreened once result is negative.
- Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) consistent with current infection.
