Phase 3 Study of CVN424
NCT Number: NCT06553027
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Parkinson Disease
Interventions: DRUG: CVN424 75 mg|DRUG: CVN424 150 mg|DRUG: Placebo
Sponsor: Cerevance
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 330
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2026-03

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.

Primary Outcome Measures: Change from Baseline to Week 12 in average daily OFF time on motor diaries for 150 mg CVN424 compared to placebo, The assessment of the average daily OFF time, normalized to waking hours will be based on diaries completed at home for three consecutive days during the 7-day period before a scheduled in-person visit., Baseline and Up to Week 12
Secondary Outcome Measures: Change from Baseline to Week 12 in the ON time without troublesome dyskinesia, The assessment of the ON time without troublesome dyskinesia will be based on diaries completed at home for three consecutive days during the 7-day period before a scheduled in-person visit., Baseline and Up to Week 12|Change from Baseline to Week 12 on the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II, The MDS-UPDRS is a comprehensive 50-question assessment of both motor and non-motor symptoms associated with PD. It features sections that require independent completion by people with PD and their caregivers, and sections to be completed by the same clinician throughout the study. Part II assess motor experiences of daily living, motor aspects of experiences of daily living. This part has 13 items. It is a self-administered questionnaire completed by the participant, which can be reviewed by the Investigator to ensure all responses are completed., Baseline and Up to Week 12|Change from Baseline to Week 12 on the Clinical Global Impression Scale - Severity (CGI-S), The CGI-S is a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal/not at all ill) to 7 (amongst the most severely ill participants). This requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. Higher scores indicate worser the illness., Baseline and Up to Week 12|Change from Baseline to Week 12 on the Patient Global Impression Scale - Severity (PGI-S), The PGI-S is a participant-completed assessment rating PD severity on a scale of 1 to 5 with 1 being none and 5 being very severe. Higher scores indicate worser the illness., Baseline and Up to Week 12|Change from Baseline to Week 12 on the MDS-UPDRS Part III, The MDS-UPDRS is a comprehensive 50-question assessment of both motor and non-motor symptoms associated with PD. It features sections that require independent completion by people with PD and their caregivers, and sections to be completed by the same clinician throughout the study. Part III consists of 33 scores based on 18 items, and each question is anchored with five response scale from 0 (normal) to 4(severe). A 0 means there is no disability, and the higher the score, the more the disability is reflected. The maximum score for Part III is 132. The total score is the sum of the numerical response values of the items. It is completed by a rater based on findings from the motor examination., Baseline and Up to Week 12|Change from Baseline to Week 12 on the Epworth Sleepiness Scale (ESS), The ESS is a participant self-administered questionnaire with 8 questions. Respondents are 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, sitting in a public place, etc. Most people engage in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life, or their "daytime sleepiness". The questionnaire takes no more than 2 or 3 minutes to answer., Baseline and Up to Week 12|Change from Baseline to Week 12 in the ON time with no dyskinesia, The assessment of the ON time with no dyskinesia will be based on diaries completed at home for three consecutive days during the 7-day period before a scheduled in-person visit., Baseline and Up to Week 12|Change from Baseline to Week 12 on the MDS-UPDRS Part I, The MDS-UPDRS is a comprehensive 50-question assessment of both motor and non-motor symptoms associated with PD. It features sections that require independent completion by people with PD and their caregivers, and sections to be completed by the same clinician throughout the study. Part I assess non-motor experiences of daily living, non-motor aspects of experiences of daily living (6 items assessed by interview and 7 items by self-assessment). It has 13 items and is further grouped into two parts: Part IA has items associated with behaviors that are assessed and completed by the rater based on information provided by the participant and caregiver. Part IB is self-administered and completed by the participant with or without assistance or input from the caregiver, but independently of the rater. Responses to both IA and IB can be reviewed by the rater to ensure information accuracy and/or provide additional information or clarification of the test items, if necessary., Baseline and Up to Week 12|Change from Baseline to Week 12 on the Parkinson's Disease Questionnaire-39 (PDQ-39), The PDQ is a 39-item self-report questionnaire that assesses eight PD-specific health related quality of life functions over the previous month. Assesses how often participants with PD experience difficulties across 8 dimensions of daily living including relationships, social situations and communication. The 39-item questionnaire offers a participant reported measure of health status and quality of life and is the most frequently used disease-specific health status measure. It also assesses the impact of PD on specific dimensions of functioning and wellbeing., Baseline and Up to Week 12|Change from Baseline to Week 12 on the Starkstein Apathy Scale, The SAS instrument is used to identify apathy in participants with PD. The scale comprises 14 questions in which the respondent self-rates on a 4-point scale, ranging from "Not at all", "Slightly", "Some", and "A Lot". Ratings are a score from 3 to 0 for questions 1-8, and from 0 to 3 for questions 9-14, producing a total score out of 42. A score above 14 is considered the more severe level of apathy., Baseline and Up to Week 12|Change from Baseline to Week 12 on the CogState digital cognitive battery, Cogstate Digital Cognitive Testing Battery are computerized cognitive assessments of attention, executive function, verbal learning, and memory. It uses standardized scores to assess participant's cognitive function. These scores are transformed into a scale where the average performance of the general population is set at 100, with a standard deviation of 15. This means that a score of 100 represents average cognitive function, while scores above or below indicate better or poorer performance, respectively, compared to the average., Baseline and Up to Week 12|Number of participants reporting treatment emergent adverse events (TEAEs), TEAEs related to moderate or severe intensity and leading to withdrawal of study drug, Up to Week 14|Number of participants reporting serious adverse events (SAEs), Up to Week 14|Number of participants with suicidal ideation as measured by Columbia Suicide Severity Rating Scale (C-SSRS), Up to Week 12|Number of participants with impulse control disorders as measured by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson 's disease Rating Scale (QUIP-RS), The QUIP-RS has 4 questions (common thoughts, urges/desires, self-control, faciliatory behaviors associated with impulse control disorders \[ICDs\]), each applied to 4 main impulse control disorders (gambling, buying, eating, and sexual behavior) and 3 related impulsivity disorders (medication use, punding, and hobbyism). Scores range from 0-4 for each question to gauge the frequency of behaviors over the preceding 4 weeks (or any defined 4-week period). Total scores range from 0 to 112., Up to Week 12|Number of participants with clinically significant changes in physical examination, vital signs, electrocardiogram (ECG) finding, and laboratory values, Up to Week 14|Percentage of completers, Up to Week 12
Other Outcome Measures: Maximum observed plasma concentration of CVN424, At Day 1, Week 2, Week 4, Week 8, and Week 12|Time to reach Cmax of CVN424, At Day 1, Week 2, Week 4, Week 8, and Week 12|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, At Day 1, Week 2, Week 4, Week 8, and Week 12|Half-life (t1/2) of CVN424, At Day 1, Week 2, Week 4, Week 8, and Week 12|Change from Baseline on the Modality virtual assessments, The Modality System is an artificial intelligence interface designed to collect information on clinical performance through audio-visual conversational technology. Participants will engage with a virtual agent via a web browser on their electronic device, completing assessments aimed at testing various functions including speech, visuo-motor skills, prosodic (stress and intonation patterns), cognitive, and linguistic abilities., Baseline and Up to Week 14