Clinical trial NCT06006247: Early Parkinson's Disease Monotherapy With CVN424
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial of CVN424 in Early Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
CVN424
Progressive neurodegenerative disorder
Parkinson's disease monotherapy
Lead sponsor: Cerevance
Sponsor class: INDUSTRY
First posted: 2023-08-23
Enrollment: 62
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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, prior documentation history, or clinical evidence of potentially unstable heart disease, including, but not limited to the following:

  1. QT interval corrected using Fridericia's formula (QTcF) \> 470 milliseconds (msec) for female participants; \> 450 msec for male participants
  2. Complete right or left bundle branch block
  3. Myocardial infarction within 1 year prior to screening, unstable angina within 6 months, or a current concern for symptomatic ischemic heart disease in the opinion of the investigator
  4. Clinically significant atrial or ventricular dysrhythmia; the heart must be in predominantly normal sinus rhythm
  5. Second- or third-degree atrioventricular (AV) block
  6. New York Heart Association (NYHA) Class II or higher congestive heart failure
  7. Clinically significant cardiomyopathy or cardiac structural abnormality, in the opinion of the investigator
  8. 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). 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.

Primary outcomes:
measure: Change from Baseline to Week 12 on the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II + Part III
timeFrame: Baseline and Up to Week 12
Secondary outcomes:
measure: Change from Baseline to Week 12 on the MDS-UPDRS Part III
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Clinical Global Impression Scale - Severity (CGI-S)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Patient Global Impression Scale - Severity (PGI-S)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the MDS-UPDRS Part II
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the MDS-UPDRS Part I
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline on the Epworth Sleepiness Scale (ESS)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline on the Non-motor Symptoms Scale (NMSS)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline on the total MDS-UPDRS
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline on the Parkinson's Disease Sleep Scale (PDSS-2)
timeFrame: Baseline and Up to Week 12
measure: Number of participants reporting treatment emergent adverse events (TEAEs), TEAEs related to moderate or severe intensity and leading to withdrawal of study drug
timeFrame: Up to Week 14
measure: Number of participants reporting serious adverse events (SAEs)
timeFrame: Up to Week 14
measure: Number of participants with clinically significant changes in physical examination, vital signs, electrocardiogram (ECG) finding, laboratory values and Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Week 14
measure: Number of participants reporting abuse related adverse events
timeFrame: Up to Week 14
measure: Number of participants with occurrences of withdrawal symptoms recorded at the follow-up visit
timeFrame: At Week 14
measure: Percentage of completers
timeFrame: Up to Week 14
Other outcomes:
measure: Change from Baseline to Week 12 on the Modality Virtual Assessment
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the CogState digital cognitive battery
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Schwab and England Activities of Daily Living (ADL)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Starkstein Apathy Scale (SAS)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Electroencephalogram (EEG) derived sleep metrics
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Parkinson's Disease Patient Report of Problems (PD-PROP™)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Personal Wellbeing Patient Report of Problems (PWB-PROP™)
timeFrame: Baseline and Up to Week 12
measure: Change from Plasma concentration of CVN424
timeFrame: Pre-dose (0 h) and at 4 h post-dose on Day 1, Week 4, 8, and 12
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Phoenix
country: United States
facility: St Joseph's Hospital and Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Muhammad Ali Parkinson Center
state: Arizona
city: Scottsdale
country: United States
facility: Movement Disorders Center of Arizona, LLC
state: Arizona
city: Palo Alto
country: United States
facility: Parkinson's Research Centers of America - Palo Alto
state: California
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research
state: Colorado
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Boca Raton
country: United States
facility: SFM Clinical Research, LLC
state: Florida
city: Orlando
country: United States
facility: N1 Research LLC
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Treatment Center of SWFL
state: Florida
city: Tampa
country: United States
facility: University of South Florida Parkinson's Disease and Movement Disorders Center
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, Dept of Neurology Kentucky Neuroscience Institute Research
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky, Center for Clinical and Translational Sciences
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital / Michigan Clinical Research Unit (MCRU) Cardiovascular Center
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Department of Neurology
state: Michigan
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Golden Valley
country: United States
facility: Struthers Parkinson's Center
state: Minnesota
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Commack
country: United States
facility: Parkinson's Research Centers of America - Long Island
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Riverhills Healthcare, Inc dba Riverhills Neuroscience
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Department of Neurology - Madden Center for Parkinson Disease and Other Movement Disorders
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: Martha Morehouse Medical Plaza
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Memphis
country: United States
facility: Veracity Neuroscience
state: Tennessee
city: Cypress
country: United States
facility: Horizon Clinical Research Group
state: Texas
city: Georgetown
country: United States
facility: Texas Movement Disorder Specialists, PLLC
state: Texas
city: Houston
country: United States
facility: Gill Neuroscience
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Fairfax
country: United States
facility: Inova Neurology - Fairfax
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
city: Kirkland
country: United States
facility: EvergreenHealth Neuroscience Institute
state: Washington
city: Kirkland
country: United States
facility: EvergreenHealth Research Department
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital Department of Neurology
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Department of Neurology
state: Wisconsin
Study officials:
References: