Study of CVN424 in Parkinson's Disease Patients With Motor Fluctuations

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of CVN424 in Parkinson's Disease Patients With Motor Fluctuations

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04191577

Enrollment

136

Registered

2019-12-10

Start date

2019-12-02

Completion date

2021-12-13

Last updated

2024-07-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson Disease

Brief summary

This is a phase 2 study, randomized, double-blind, placebo-controlled, multicenter study of oral CVN424 at two dose levels (low-dose and high-dose) in Parkinson's disease (PD) patients with motor fluctuations.

Detailed description

Approximately 135 male and female subjects with Parkinson's disease, on a stable dosage of levodopa but with an average of ≥ 2 h total OFF time/day and not less than 1 h per day, will be enrolled. Following baseline safety and efficacy assessments, subjects will be randomized to receive once-daily doses of either low-dose CVN424, high-dose CVN424, or matching placebo. All subjects not randomized to placebo will initiate treatment with a low-dose of CVN424 on Day 1; the low-dose arm will continue to receive their low dose each day, while the high-dose arm will increase their daily dosage to the high-dose CVN424 beginning on Day 8 ±2 days and continuing thereafter. Study drug will be self-administered each morning as an oral suspension. Subjects will continue their other PD medications.

Interventions

DRUGCVN424 Low Dose

CVN424

DRUGCVN424 High Dose

CVN424

DRUGPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Intervention model description

Planned dose levels are placebo, low dose, and high dose of CVN424. Study drug dispensed as CVN424 suspension (or matching placebo) in amber glass bottles suitable for self-administered dosing.

Eligibility

Sex/Gender

ALL

Age

30 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Male or female adult who is 30 to 80 years of age inclusive at study entry. * Has idiopathic Parkinson's disease, Hoehn and Yahr stages 2-4, and is on a stable dosage of levodopa. * Experiences an average of at least 2 h total OFF time/day, and at least 1 h each day, per Patient Motor Diary over 2 days during Screening assessment. * The subject signs and dates a written informed consent form (ICF) and any required privacy authorization prior to the initiation of any study procedures.

Exclusion criteria

* Has atypical parkinsonism, severe disabling dyskinesia, or severe motor fluctuations that the investigator considers likely to interfere with study participation or assessments, or history of implant for Deep Brain Stimulation. * Poor concordance (\<75%) of self-report with site rater on in-clinic Screening period Patient Motor Diary. Subjects with low concordance may be retested after further instruction, at investigator's discretion. * Screening period Patient Motor Diary scored at-home over 2 days demonstrates unacceptable quality of the diary, with more than 4 errors per day. (Assistance from caregivers is permitted if they also will be providing assistance with home Patient Motor Diary entries for Day 15 and 27 efficacy assessments.) Subjects with more than 4 errors per day may be retested after further instruction, at investigator's discretion. * Body mass index (BMI) at Screening \<18.0 or \>35.0 kg/m2, inclusive. * Subject has evidence of Clinically significant neurologic or other disorder or impairment that, in opinion of Investigator, is reasonably expected to impact the ability of the subject to participate or to confound the study results. * Subject has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention known to impact absorption \[e.g., bariatric surgery or bowel resection\]). * Subject has a history of cancer or other malignancy, with the exception of low-grade cervical intraepithelial neoplasia, low-grade (low-risk) prostate cancer, or 5-year cancer-free survivors of basal or squamous cell carcinoma, higher-grade cervical intraepithelial neoplasia or prostate cancer. * Has a history of human immunodeficiency virus (HIV) infection. * Subject has a supine blood pressure outside the ranges of 80 to 160 mm Hg for systolic and 50 to 100 mm Hg for diastolic, confirmed with up to two repeat tests, at the Screening Visit; or symptomatic orthostatic hypotension, in the opinion of the investigator. * Subject has a resting heart rate outside the range 50 to 100 bpm, confirmed with up to two repeat tests, at the Screening Visit. * Positive urine result for illegal drugs (except cannabis) at Screening, or history of illegal drug use (except cannabis) or alcohol abuse within 1 year prior to the Screening Visit. * Subject has received any investigational compound (defined as a drug that has not been FDA-approved) within 30 days prior to the first dose of study medication, or within 5 half-lives of the investigational compound, whichever is greater. * Subject has, within the prior month, ingested any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table as listed in Table 2. * Male subjects who do not agree to all the following rules: when sexually active with female partner(s) of childbearing potential during the study and for 12 weeks after the last dose of study drug: a) use an acceptable method of birth control (condom with spermicide or surgical sterilization) and b) refrain from sexual activity with female partners who do not use an acceptable method of birth control. Barrier contraception (condom with spermicide) must be used by all male subjects who were not surgically sterilized at least 90 days prior to screening. Male subjects must also agree to refrain from sperm donation during the study and until 12 weeks after the last dose of study drug. * Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova during the study or for 30 days after the last dose of study drug. Women of childbearing potential (WOCBP) also must be practicing an adequate method of birth control (e.g., oral or parenteral contraceptives, intrauterine device, barrier, abstinence). * Risk of suicide according to the investigator's clinical judgment or has made a suicide attempt in the previous 3 years. * Subject is a study site employee or an immediate family member of a study site employee

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Study Drug	Up to Day 35	An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as any event with onset during or after the first dose of study treatment (active or placebo).

Secondary

Measure	Time frame	Description
Percentage of Participants With Clinically Significant Abnormal Laboratory Parameters	Up to Day 35	Blood and urine samples were collected for the analysis of laboratory parameters including clinical chemistry, hematology, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Percentage of Participants With Clinically Significant Changes 12-Lead Electrocardiogram (ECG) Findings	Up to Day 35	12-lead ECG recordings including heart rate and measured PR, QRS, QT, QT interval with Fridericia's correction method (QTcF) and QT interval with Bazett's correction method (QTcB) intervals. 12-lead ECG recordings were obtained after participants rested for at least 5 minutes in supine position. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Percentage of Participants With Clinically Significant Abnormal Vital Signs	Up to Day 35	Vital signs including blood pressure (systolic and diastolic blood pressure), pulse rate, body temperature, respiratory rate and weight were measured after participants rested for at least 5 minutes in supine position. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Change From Baseline in 2-day Average OFF Time	Baseline and at Day 27	The Patient Motor Diary data (Hauser Diary) was completed by the participant to record the broad motor symptoms of pharmacodynamics. Categories included time asleep, OFF time, ON time without dyskinesia, ON time with non-troublesome dyskinesia, and ON time with troublesome dyskinesia. These diaries were collected for 24 hours on each of 2 consecutive days with records for every 30 minutes interval. The average daily OFF time was calculated from the records with reported OFF time. Baseline was defined as Day 0. Change from Baseline was defined as post Baseline minus Baseline value.

Countries

United States

Participant flow

Recruitment details

21 study sites in the United States

Participants by arm

Arm	Count
Placebo Arm Participants were randomized in a 1:1:1 ratio into 1 of 3 study arms to receive either once daily (QD) low-dose CVN424 (50 milligrams \[mg\]), high-dose CVN424 (150 mg), or matching placebo.	44
CVN424 50 mg Participants were randomized in a 1:1:1 ratio into 1 of 3 study arms to receive either QD low-dose CVN424 (50 mg), high-dose CVN424 (150 mg), or matching placebo.	45
CVN424 150 mg Participants were randomized in a 1:1:1 ratio into 1 of 3 study arms to receive either QD low-dose CVN424 (50 mg), high-dose CVN424 (150 mg), or matching placebo.	47
Total	136

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	0	0	1
Overall Study	Death	0	0	1
Overall Study	Physician Decision	1	1	0
Overall Study	Withdrawal by Subject	2	2	1

Baseline characteristics

Characteristic	Placebo Arm	CVN424 50 mg	CVN424 150 mg	Total
Age, Continuous	67.0 years STANDARD_DEVIATION 7.1	63.0 years STANDARD_DEVIATION 7.67	65.6 years STANDARD_DEVIATION 9.05	65.2 years STANDARD_DEVIATION 8.12
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) Black or African American	1 Participants	3 Participants	1 Participants	5 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	42 Participants	41 Participants	46 Participants	129 Participants
Sex: Female, Male Female	10 Participants	12 Participants	20 Participants	42 Participants
Sex: Female, Male Male	34 Participants	33 Participants	27 Participants	94 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 44	0 / 45	1 / 47
other Total, other adverse events	4 / 44	8 / 45	9 / 47
serious Total, serious adverse events	0 / 44	0 / 45	1 / 47

Arm	Measure	Value (NUMBER)
Placebo Arm	Percentage of Participants With Clinically Significant Changes 12-Lead Electrocardiogram (ECG) Findings	0 Percentage of participants
CVN424 50 mg	Percentage of Participants With Clinically Significant Changes 12-Lead Electrocardiogram (ECG) Findings	0 Percentage of participants
CVN424 150 mg	Percentage of Participants With Clinically Significant Changes 12-Lead Electrocardiogram (ECG) Findings	0 Percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 6, 2026