Early Parkinson's Disease Monotherapy With CVN424

Cerevance Beta, Inc.64 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Parkinson's Disease

Interventions

CVN424 150 mgDRUG

Participants will receive 1 CVN424 tablet (150 mg) per day.

PlaceboDRUG

Participants will receive 1 matching placebo tablet per day.

Eligibility

Sex: ALLMin age: 30 Years

Medical Language ↔ Plain English

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.

Locations (42)

Outcomes

Primary Outcomes

Change From Baseline to Week 12 on the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II + Part III

MDS-UPDRS was a comprehensive 50-question assessment designed to evaluate both motor and non-motor symptoms associated with PD. It included sections that were independently completed by individuals with PD and their caregivers, as well as sections that were consistently completed by the same approved rater throughout the study. Parts II and III were used in this study. Part II (13 items; range 0-52) assesses motor experiences of daily living and is completed by participants. Part III (33 scores from 18 items; range 0-132) assesses motor signs and is rated by the same qualified rater. Each item is scored 0-4 (0 = Normal, 4 = Severe). The combined possible score for Parts II and III is 184. The total score was calculated as (Sum of available item scores/Number of items with non-missing scores) × 13 for Part II and × 33 for Part III. Higher score indicates more severe symptoms of PD. Baseline was the value on Day 1. Change from Baseline (CFB) = Observed value - Baseline Value.

Time frame: Baseline (Day 1) and Up to Week 12

Secondary Outcomes

Change From Baseline to Week 12 on the MDS-UPDRS Part III

MDS-UPDRS was a comprehensive 50-question assessment that evaluated both motor and non-motor symptoms associated with PD. It included sections that were independently completed by individuals and their caregivers, as well as sections that were consistently completed by the same clinician throughout the study. Part III assesses the motor signs of PD and is administered by the rater. It contains 33 scores based on 18 items. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. Maximum score for Part III was 132. Total score represented sum of the numerical response values for all items. The MDS-UPDRS Part III sum score was calculated as: (Sum of available item scores) / (Number of items with non-missing scores) × 33. Higher score indicates more severe symptoms of PD. Baseline was the value on Day 1. CFB = Observed value - Baseline Value.

Time frame: Baseline (Day 1) and Up to Week 12

Change From Baseline to Week 12 on the Clinical Global Impression Scale - Severity (CGI-S)

Data from ClinicalTrials.gov

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Barrow Neurological Institute

Phoenix, Arizona, United States

St Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Muhammad Ali Parkinson Center

Phoenix, Arizona, United States

Movement Disorders Center of Arizona, LLC

Scottsdale, Arizona, United States

Parkinson's Research Centers of America - Palo Alto

Palo Alto, California, United States

CenExel Rocky Mountain Clinical Research

Englewood, Colorado, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

SFM Clinical Research, LLC

Boca Raton, Florida, United States

N1 Research LLC

Orlando, Florida, United States

...and 32 more locations

The CGI-S was a 7-point scale used to assess the severity of illness, with response options ranging from 0 (not assessed), 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill subjects). The CGI-S score represents the numerical rating assigned by the clinician, reflecting the participant's illness severity at the time of assessment, based on the clinician's prior experience with individuals with the same diagnosis. Higher scores reflected greater severity of illness. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Time frame: Baseline (Day 1) and Up to Week 12

Change From Baseline to Week 12 on the Patient Global Impression Scale - Severity (PGI-S)

The PGI-S was a participant-completed assessment that rated PD severity on a scale of 1 to 5; 1 being none and 5 being very severe. The scores ranging from 1 (none), 2 (mild), 3 (moderate), 4 (severe) and 5 (very severe). Higher scores reflected greater illness severity. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Time frame: Baseline (Day 1) and Up to Week 12

Change From Baseline to Week 12 on the MDS-UPDRS Part II

MDS-UPDRS was a comprehensive 50-question assessment that evaluated both motor and non-motor symptoms associated with PD. It included sections that were independently completed by individuals and their caregivers, as well as sections that were consistently completed by the same clinician throughout the study. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. It was a self-administered questionnaire completed by the participant, which was reviewed by the Investigator to ensure that all responses were properly completed. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The total score ranged from 0 to 52 and was calculated as (Sum of available item scores/Number of items with non-missing scores) × 13. A higher score indicates more severe symptoms of PD. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Time frame: Baseline (Day 1) and Up to Week 12

Change From Baseline to Week 12 on the MDS-UPDRS Part I

The MDS-UPDRS was a comprehensive 50-question assessment that evaluated both motor and non-motor symptoms associated with PD. It included sections that were independently completed by individuals with PD and their caregivers, and by the same clinician throughout the study. Part I assessed non-motor aspects of experiences of daily living and consisted of 13 items, divided into two subparts. Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The MDS UPDRS Part I sum score ranges from 0 to 52 and was calculated as (Sum of available item scores/Number of items with non-missing scores) × 13. A higher score indicated more severe symptoms of PD. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Time frame: Baseline (Day 1) and Up to Week 12

Change From Baseline on the Epworth Sleepiness Scale (ESS)

The ESS is a participant self-administered questionnaire consisting of 8 questions. Respondents were asked to rate, on a 4-point scale (0 to 3: would never doze, slight chance of dozing, moderate chance of dozing, and high chance of dozing), their usual chances of dozing off or falling asleep while engaged in eight different activities, such as sitting and reading, watching television, or sitting in a public place. Most individuals engaged in these activities at least occasionally, though not necessarily on a daily basis. The ESS score was calculated as the sum of the 8 item scores, ranged from 0 to 24. Higher scores indicated a greater average sleep propensity in daily life or increased daytime sleepiness. The questionnaire typically takes not more than 2 to 3 minutes to complete. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Time frame: Baseline (Day 1) and Up to Week 12

Change From Baseline on the Non-motor Symptoms Scale (NMSS)

The NMSS is a 30-item rater-based instrument used to assess the frequency and severity of non-motor symptoms in participants across all stages of PD. The scale evaluates symptom burden across nine domains: cardiovascular (including falls), sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, sexual function, and miscellaneous. Responses were used to quantify symptoms based on two scales, severity (ranging from 0-3) and frequency (ranging from 0-4). The item score is calculated by multiplying frequency by severity. The total NMSS score is the sum of all 30 item scores (ranging from 0 to 360), with lower scores indicating fewer non-motor symptoms. The assessment is administered by a trained rater. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Time frame: Baseline (Day 1) and Up to Week 12

Change From Baseline in Sum of MDS-UPDRS of Parts I, II, and III

Parts I, II, and III of the International Parkinson and MDS-UPDRS evaluates motor (Parts I and III) and non-motor (Part II) experiences and complications of PD by which it characterizes the extent and burden of disease. Questions/evaluations are divided across Part I (13 questions, 52 possible points), Part II (13 questions, 52 possible points), Part III (33 questions based on 18 items, several with right, left or other body distribution scores, 132 possible points) and summed. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe for a total possible score of 236. A positive change in scores between Baseline to Week 12 indicates symptom/disease worsening. A negative change in score between Baseline to Week 12 indicates symptom/disease improvement. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Time frame: Baseline (Day 1) and Up to Week 12

Change From Baseline on the Parkinson's Disease Sleep Scale (PDSS-2)

The PDSS-2 is a 15-item participant-reported outcome measure used to assess nocturnal disturbances in PD. It employed a 5-point frequency scale ranging from "very often" (0) to "never" (4). The total score ranged from 0 to 60, with higher scores indicating greater impairment. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Time frame: Baseline (Day 1) and Up to Week 12

Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical trial subject who had been administered a medicinal product, and which did not necessarily have to bear a causal relationship with the treatment. A TEAE was an AE that began on or after administration of the first dose of the study drug or represented an increase in severity or frequency occurring on or after the first dose. A serious adverse event (SAE) was any untoward medical occurrence during a clinical trial that resulted in significant harm or risk to a participant.

Time frame: Up to Week 12

Number of Participants Reporting TEAE by Severity

A TEAE was an AE that began on or after administration of the first dose of the study drug or represented an increase in severity or frequency occurring on or after the first dose. The severity of TEAEs is reported as indicated on the electronic case report form (eCRF) by the Investigator where mild indicates asymptomatic or mild symptoms; no intervention indicated; moderate: Minimal, local, or non-invasive intervention indicated; Severe: Medically significant but not immediately life-threatening.

Time frame: Up to Week 12

Number of Participants Reporting TEAEs Leading to Withdrawal of Study Drug

A TEAE was an AE that began on or after administration of the first dose of the study drug or represented an increase in severity or frequency occurring on or after the first dose.

Time frame: Up to Week 12

Number of Participants With Clinically Significant Changes in Physical Examination

A comprehensive physical examination will be conducted by a qualified physician, encompassing measurements of body weight and height, assessment of general appearance, and evaluation of the head, ears, eyes, nose, throat, mouth, neck, heart, lungs, abdomen, musculoskeletal and neurological systems, extremities, and skin.

Time frame: Up to Week 12

Number of Participants With Clinically Significant Changes in Vital Signs

Vital signs included temperature, respiration rate, heart rate, and blood pressure, and were collected at the specified timepoints. Blood pressure was measured after participants had remained in a supine position for at least 5 minutes, and again within 1 to 3 minutes of standing.

Time frame: Up to Week 12

Number of Participants With Occurrences of Withdrawal Symptoms Recorded at the Follow-up Visit

Participants had chose to withdraw from (i.e., discontinue his or her participation in) an ongoing research study, or when an investigator terminated a participant's participation.

Time frame: At Week 14

Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)

Twelve-lead ECGs were recorded using an ECG machine that automatically calculated the heart rate and measured the PR interval, RR interval, QRS interval, QT interval, and QTcF (QT Interval Corrected Using Fridericia's Formula) and QTcB intervals (QT interval corrected by Bazett's formula). ECG recordings were obtained with participants in a supine position following an approximately 10-minute period of rest.

Time frame: Up to Week 12

Number of Participants With Clinically Significant Changes in Serum Chemistry Parameters

Blood samples were collected for the assessment of alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, carbon dioxide, chloride, choriogonadotropin beta, creatine kinase, creatinine, direct bilirubin, gamma glutamyl transferase, glomerular filtration rate, glucose, lactate dehydrogenase, potassium, protein, sodium, urea nitrogen.

Time frame: Up to Week 12

Number of Participants With Clinically Significant Changes in Hematology Parameters

Blood samples were collected for the assessment of complete blood count (CBC) including hemoglobin, platelet count, and white blood cell counts, and differential to include the absolute counts for neutrophils, lymphocytes, eosinophils, and monocytes.

Time frame: Up to Week 12

Number of Participants Reporting Abuse Related TEAE

If a participant had used controlled prescription drugs and over-the-counter medications for purposes not prescribed or intended such as to get high, feel stimulated or sedated; taken more of the substance than prescribed or recommended; or taken the substance too often or for a longer period of time than was prescribed or recommended.

Time frame: Up to Week 12

Percentage of Participants Who Completed the Study

Included all participants who had completed the study treatment for 12 weeks and had the corresponding Week 12 efficacy assessment.

Time frame: At Week 12

Number of Participants Who Reported at Least One Positive Columbia Suicide Severity Rating Scale (C-SSRS)

Suicidal ideation and behavior were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), a validated tool for evaluating the presence and severity of suicide risk. The C-SSRS rates suicidal ideation on a 5-point scale, where 1 indicates a wish to be dead (passive ideation) and 5 represents active suicidal ideation with specific plan and intent (the highest severity). Higher scores reflect greater suicidal risk. In addition to ideation, the C-SSRS captures the presence or absence of suicidal behaviors, including actual attempts, interrupted or aborted attempts, and preparatory acts or behaviors. Suicidal behaviors are summarized categorically (Yes/No) and reported as the number and percentage of participants exhibiting each type.

Time frame: Baseline (Day 1) and Up to Week 12

Number of Participants With Related TEAEs in Relationship to Study Drug

An AE was defined as any untoward medical occurrence in a participant or clinical trial subject who had been administered a medicinal product, and which did not necessarily have to bear a causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease that was temporally associated with the use of a medicinal product, regardless of whether it was considered related to the product. A TEAE was an AE that began on or after administration of the first dose of the study drug or represented an increase in severity or frequency occurring on or after the first dose.

Time frame: Up to Week 12