NCT06006247

Early Parkinson's Disease Monotherapy With CVN424

Completed Phase 2 Results posted Last updated 23 March 2026

What this trial tests

Phase 2 trial testing CVN424 150 mg in Parkinson's Disease in 64 participants. Completed in 13 February 2025.

Timeline

11 September 2023

Primary endpoint
30 January 2025

13 February 2025

Quick facts

Lead sponsor	Cerevance Beta, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	64
Start date	11 September 2023
Primary completion	30 January 2025
Estimated completion	13 February 2025
Sites	42 locations across United States

Drugs / interventions tested

• CVN424 150 mg — full drug profile →
• Placebo

Conditions studied

• Parkinson's Disease — all drugs for Parkinson's Disease →

Sponsor

Cerevance Beta, Inc. — full company profile →

Who can join

30 and older, any sex, with Parkinson's Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline to Week 12 on the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II + Part III Primary · Baseline (Day 1) and Up to Week 12

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

Group	Value	95% CI
CVN424 150 mg	-2.81	± 1.599
Placebo	-2.09	± 1.622

Change From Baseline to Week 12 on the MDS-UPDRS Part III Secondary · Baseline (Day 1) and Up to Week 12

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

Group	Value	95% CI
CVN424 150 mg	-2.5	± 1.35
Placebo	-2.1	± 1.37

Change From Baseline to Week 12 on the Clinical Global Impression Scale - Severity (CGI-S) Secondary · Baseline (Day 1) and Up to Week 12

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 val

Group	Value	95% CI
CVN424 150 mg	-0.1	± 0.59
Placebo	-0.1	± 0.43

Change From Baseline to Week 12 on the Patient Global Impression Scale - Severity (PGI-S) Secondary · Baseline (Day 1) and Up to Week 12

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

Group	Value	95% CI
CVN424 150 mg	0.1	± 0.62
Placebo	0.0	± 0.63

Change From Baseline to Week 12 on the MDS-UPDRS Part II Secondary · Baseline (Day 1) and Up to Week 12

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

Group	Value	95% CI
CVN424 150 mg	-0.3	± 0.50
Placebo	0.0	± 0.51

Change From Baseline to Week 12 on the MDS-UPDRS Part I Secondary · Baseline (Day 1) and Up to Week 12

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

Group	Value	95% CI
CVN424 150 mg	-1.0	± 0.61
Placebo	0.4	± 0.62

Change From Baseline on the Epworth Sleepiness Scale (ESS) Secondary · Baseline (Day 1) and Up to Week 12

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 fro

Group	Value	95% CI
CVN424 150 mg	-0.4	± 0.41
Placebo	-0.1	± 0.42

Change From Baseline on the Non-motor Symptoms Scale (NMSS) Secondary · Baseline (Day 1) and Up to Week 12

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

Group	Value	95% CI
CVN424 150 mg	-1.4	± 2.22
Placebo	0.3	± 2.25

Change From Baseline in Sum of MDS-UPDRS of Parts I, II, and III Secondary · Baseline (Day 1) and Up to Week 12

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 =

Group	Value	95% CI
CVN424 150 mg	-3.8	± 1.96
Placebo	-1.8	± 1.99

Change From Baseline on the Parkinson's Disease Sleep Scale (PDSS-2) Secondary · Baseline (Day 1) and Up to Week 12

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

Group	Value	95% CI
CVN424 150 mg	-1.0	± 0.95
Placebo	-0.2	± 0.97

Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Secondary · Up to Week 12

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.

Any TEAE

Group	Value	95% CI
CVN424 150 mg	21
Placebo	20

Any Serious TEAE

Group	Value	95% CI
CVN424 150 mg	0
Placebo	2

Number of Participants Reporting TEAE by Severity Secondary · Up to Week 12

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.

Mild

Group	Value	95% CI
CVN424 150 mg	18
Placebo	19

Moderate

Group	Value	95% CI
CVN424 150 mg	4
Placebo	7

Severe

Group	Value	95% CI
CVN424 150 mg	1
Placebo	1

Moderate or Severe

Group	Value	95% CI
CVN424 150 mg	5
Placebo	7

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Week 12. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CVN424 150 mg

Serious: 0/32 (0%)

Deaths: 0/32

Placebo

Serious: 2/32 (6%)

Deaths: 0/32

Serious adverse events (2 terms)

Reaction	System	CVN424 150 mg	Placebo
Angina Unstable	Cardiac disorders	—	—
Chest pain	Cardiac disorders	—	—

Other adverse events (75 terms — click to expand)

Reaction	System	CVN424 150 mg	Placebo
Dizziness	Nervous system disorders	—	—
Insomnia	Nervous system disorders	—	—
Orthostatic hypotension	Vascular disorders	—	—
COVID-19	Infections and infestations	—	—
Headache	Nervous system disorders	—	—
Tremor	Nervous system disorders	—	—
Chest pain	General disorders	—	—
Fatigue	General disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Pain	General disorders	—	—
Blood creatine phosphokinase increased	Investigations	—	—
Cognitive disorder	Nervous system disorders	—	—
Hypoaesthesia	Nervous system disorders	—	—
Parkinson's Disease	Nervous system disorders	—	—
Hyposmia	Nervous system disorders	—	—
Paraesthesia oral	Nervous system disorders	—	—
Somnolence	Nervous system disorders	—	—
Vertigo	Nervous system disorders	—	—
Vision blurred	Nervous system disorders	—	—
Asthenia	General disorders	—	—
Energy increased	General disorders	—	—
Hyperhidrosis	General disorders	—	—
Malaise	General disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Abdominal distension	Gastrointestinal disorders	—	—
Abdominal hernia	Gastrointestinal disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Gastrointestinal bacterial overgrowth	Gastrointestinal disorders	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Muscle twitching	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Fractured coccyx	Musculoskeletal and connective tissue disorders	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Muscle strain	Musculoskeletal and connective tissue disorders	—	—
Blood pressure increased	Investigations	—	—
Gamma-glutamyltransferase increased	Investigations	—	—

Most-reported serious reactions: Angina Unstable, Chest pain.

Data from ClinicalTrials.gov NCT06006247 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. CVN424, a GPR6 inverse agonist, for Parkinson's disease and motor fluctuations: a double-blind, randomized, phase 2 trial.
   Brice NL, Carlton M, Margolin DH, Bexon M, et al · · 2024 · cited 5× · PMID 39469536 · DOI 10.1016/j.eclinm.2024.102882
2. Nanotherapeutic Interventions for Parkinson's Disease: Modulating Pathogenic Mechanisms and Overcoming Therapeutic Obstacles.
   Yin X, Wang C, Lin W, Huang S, et al · · 2026 · PMID 41907367 · DOI 10.2147/ijn.s570452