Clinical trial NCT06553027: To Evaluate the Efficacy of CVN424 in Parkinson's Disease Participants With Motor Complications
Official title: Phase 3, Randomized, Double-Blind, Placebo-Controlled Multicenter Study of CVN424 in Parkinson's Disease Patients With Motor Complications
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Parkinson Disease
Keywords: Parkinson Disease
CVN424
Phase 3
Motor fluctuations
Idiopathic Parkinson Disease
Lead sponsor: Cerevance
Sponsor class: INDUSTRY
First posted: 2024-08-14
Enrollment: 330
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 randomized, double-blind, placebo-controlled, multicenter study in participants with Parkinson's disease (PD) with motor fluctuations. Participants will be randomized to receive once-daily oral doses of either 75 milligrams (mg) CVN424, 150 mg CVN424, or a matching placebo for 12 weeks. Participants who successfully complete this study and retain eligibility/suitability will be invited to participate in a future open-label extension (OLE) study.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of PD consistent with United Kingdom (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.
* Body Mass Index (BMI) \> 18.0 and \< 35.0 Kilograms per meter square (kg/m\^2), 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)7 Score of at least 24.
* PD medications must be stable for at least 4 weeks prior to Screening; monoamine oxidase B (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).
* 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 with a blinded rater) 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.
* Severe or disabling dyskinesias or OFF expected to preclude successful study participation, in the opinion of the investigator.
* Any previous procedure or therapy designed to provide continuous levodopa or stimulation of dopaminergic tone (i.e., Duopa, apomorphine), 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)
* Use of injectable botulinum medication for sialorrhea within 90 days of screening or during the study.
* 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.
* 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 (opiates, tetrahydrocannabinol \[THC\], methadone, cocaine, and amphetamines \[including ecstasy\]).
* Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN).
* Significant renal impairment as determined by estimated glomerular filtration rate (eGFR) less than or equal to 55 millilitres per minute (ml/min).
* Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCV) antibody, or Human Immunodeficiency Virus (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 investigational medicinal product (IMP) or medical device in the last 3 months or within 5 half-lives of the IMP (whichever is longer) prior to Screening.

Primary outcomes:
measure: Change from Baseline to Week 12 in average daily OFF time on motor diaries for 150 mg CVN424 compared to placebo
timeFrame: Baseline and Up to Week 12
Secondary outcomes:
measure: Change from Baseline to Week 12 in the ON time without troublesome dyskinesia
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II
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 III
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Epworth Sleepiness Scale (ESS)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 in the ON time with no dyskinesia
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 to Week 12 on the Parkinson's Disease Questionnaire-39 (PDQ-39)
timeFrame: Baseline and Up to Week 12
measure: Change from Baseline to Week 12 on the Starkstein Apathy Scale
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: 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 suicidal ideation as measured by Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Week 12
measure: Number of participants with impulse control disorders as measured by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson 's disease Rating Scale (QUIP-RS)
timeFrame: Up to Week 12
measure: Number of participants with clinically significant changes in physical examination, vital signs, electrocardiogram (ECG) finding, and laboratory values
timeFrame: Up to Week 14
measure: Percentage of completers
timeFrame: Up to Week 12
Other outcomes:
measure: Maximum observed plasma concentration of CVN424
timeFrame: At Day 1, Week 2, Week 4, Week 8, and Week 12
measure: Time to reach Cmax of CVN424
timeFrame: At Day 1, Week 2, Week 4, Week 8, and Week 12
measure: Area under the plasma concentration-time curve from time 0 (time of dosing) to last time of sample collection hours (AUC 0-last) of CVN424
timeFrame: At Day 1, Week 2, Week 4, Week 8, and Week 12
measure: Half-life (t1/2) of CVN424
timeFrame: At Day 1, Week 2, Week 4, Week 8, and Week 12
measure: Change from Baseline on the Modality virtual assessments
timeFrame: Baseline and Up to Week 14
Locations:
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: Maitland
country: United States
facility: K2 Medical Research
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: N1 Research LLc
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Center of SWFL
state: Florida
city: Port Orange
country: United States
facility: University Clinical Research-DeLand, LLC d/b/a Accel Research Sites - Brain & Spine Institute
state: Florida
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: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Hopewell
country: United States
facility: Boro Neurology
state: New Jersey
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 Medical College
state: New York
city: Durham
country: United States
facility: Duke Neurology Morreene Road Clinic
state: North Carolina
city: Cincinnati
country: United States
facility: Riverhills Healthcare, Inc dba Riverhills Neuroscience
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma
state: Oklahoma
city: Memphis
country: United States
facility: Veracity Neuroscience LLC
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: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Manila
country: Philippines
facility: University of the Philippines - College of Medicine
state: Ermita
Study officials:
References: