Phase 3, Randomized, Double-Blind, Placebo-Controlled Multicenter Study of CVN424 in Parkinson's Disease Patients With Motor Complications
Trial ID: NCT06553027
Status: ACTIVE_NOT_RECRUITING
Study type: INTERVENTIONAL
Phase: PHASE3
Start date: 2024-09-20
Completion date: 2026-08
Sponsor: Cerevance
Conditions: Parkinson Disease
Interventions: CVN424 75 mg; CVN424 150 mg; Placebo
Locations: The Kirklin Clinic of UAB Hospital; University of Alabama at Birmingham; University of Alabama at Birmingham ALS Clinic; Barrow Neurological Institute; Muhammad Ali Parkinson Center; St. Joseph's Hospital and Medical Center; Parkinson's Research Centers of America - Orange county; Parkinson's Research Centers of America - Orange County; Parkinson's Research Centers of America - Palo Alto; CenExel Rocky Mountain Clinical Research; David and Rhoda Chase Family Movement Disorders Center - Vernon; Parkinson's Disease and Movement Disorders Center of Boca Raton; SFM Clinical Research, LLC; K2 Medical Research; Renstar Medical Research; N1 Research LLc; Parkinson's Disease Center of SWFL; University Clinical Research-DeLand, LLC d/b/a Accel Research Sites - Brain & Spine Institute; USF Parkinson's Disease and Movement Disorders Center; Atlanta Neuroscience Institute; University of Kansas Medical Center; University of Kentucky, Dept of Neurology Kentucky Neuroscience Institute Research; Boston Clinical Trials; University of Michigan Dept. of Neurology; University of Michigan Hospital - Michigan Clinical Research Unit (MCRU); Quest Research Institute; Boro Neurology; Global Neurosciences Institute at Pennington; Parkinson's Research Centers of America - Long Island; Weill Cornell Medical College; The Neurological Institute; Duke Neurology Morreene Road Clinic; Raleigh Neurology Associates; Velocity Clinical Research; Riverhills Healthcare, Inc dba Riverhills Neuroscience; The Ohio State University Wexner Medical Center; The Ohio State University - Martha Morehouse Medical Plaza; The Movement Disorder Clinic of Oklahoma; Oregon Health and Science University; Medical University of South Carolina; Veracity Neuroscience LLC; Horizon Clinical Research Group; Texas Movement Disorder Specialists, PLLC; Houston Methodist Neurological Institute; Gill Neuroscience; Central Texas Neurology Consultants; Inova Parkinson's and Movement Disorders Center - Alexandria; Inova Neurology - Fairfax; Inova Fairfax Medical Campus; Henrico Doctors Neurology Associates, LLC; EvergreenHealth Research Department; Inland Northwest Research; Medical College of Wisconsin-Department of Neurology; St Vincent's Hospital Sydney; Southern Neurology; Westmead Hospital-Department of Neurology; Princess Alexandra Hospital; Monash Health; The Alfred; Perron Institute for Neurological and Translational Science; Nemocnice Pardubického kraje, a.s. - Pardubická nemocnice; Vseobecna Fakultni Nemocnice v Praze; Praglandia s.r.o.; Axon Clinical s.r.o.; Fakultní Nemocnice u sv. Anny v Brně; Neurologie Taláb Radomír Doc. MUDr., CSc; Vseobecna Fakultni Nemocnice v Praze; Hôpital Pierre Wertheimer; Hôpital Pierre-Paul Riquet; Hôpital Gui de Chauliac; Hôpital Roger Salengro; Hôpitaux Universitaires Henri Mondor; San Raffaele Cassino; Azienda Ospedale Università di Padova; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - San Raffaele Pisana; Centrum Zdrowia i Urody MAXXMED; ETG Neuroscience Sp. z o. o; Neuro-Care Centrum Medyczne; Neurologia Śląska Centrum Medyczne; Wielospecjalistyczna Poradnia Lekarska Synapsis; The Alliance Hispanic Alliance for Clinical and Translational Research; Universidad de Puerto Rico Recinto de Ciencias Médicas; Hospital Universitario Virgen del Rocío; Hospital Universitari General de Catalunya; Hospital Universitario Cruces; Policlínica Gipuzkoa; Hospital Universitari i Politècnic La Fe; Hospital Clinic de Barcelona; Hospital de la Santa Creu i Sant Pau; Hospital Universitario de La Princesa; Newcastle Upon Tyne Hospitals NHS Foundation Trust; Northern Care Alliance NHS Foundation Trust; King's College Hospital NHS Foundation Trust; University Hospitals Plymouth NHS Trust
Countries: United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; United States; Australia; Australia; Australia; Australia; Australia; Australia; Australia; Czechia; Czechia; Czechia; Czechia; Czechia; Czechia; Czechia; France; France; France; France; France; Italy; Italy; Italy; Poland; Poland; Poland; Poland; Poland; Puerto Rico; Puerto Rico; Spain; Spain; Spain; Spain; Spain; Spain; Spain; Spain; United Kingdom; United Kingdom; United Kingdom; United Kingdom
Enrollment: 330
Age range: 30 Years - None
Sex: ALL

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 or 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) 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 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.
* 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, 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 as three (3) or more uses per week of on-demand medication is not allowed. On demand medications should only be used for medical emergencies and should be avoided on anticipated diary days, as best as possible.
* 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. Drugs of abuse refers to illicit substances and does not include participants 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.
* 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 milliliters 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.
* A known hypersensitivity to the IMP or to any excipients used in the formulation.

Outcomes:
Change from Baseline to Week 12 in average daily OFF time on motor diaries for 150 mg CVN424 compared to placebo