Clinical trial NCT04191577: Study of CVN424 in Parkinson's Disease Patients With Motor Fluctuations
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of CVN424 in Parkinson's Disease Patients With Motor Fluctuations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Lead sponsor: Cerevance
Sponsor class: INDUSTRY
First posted: 2019-12-10
Enrollment: 136
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Study Drug
timeFrame: Up to Day 35
Secondary outcomes:
measure: Percentage of Participants With Clinically Significant Abnormal Laboratory Parameters
timeFrame: Up to Day 35
measure: Percentage of Participants With Clinically Significant Changes 12-Lead Electrocardiogram (ECG) Findings
timeFrame: Up to Day 35
measure: Percentage of Participants With Clinically Significant Abnormal Vital Signs
timeFrame: Up to Day 35
measure: Change From Baseline in 2-day Average OFF Time
timeFrame: Baseline and at Day 27
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Pasadena
country: United States
facility: SC3 Research - Pasadena
state: California
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Bradenton
country: United States
facility: Nova Clinical Research
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Treatment Center of SW Florida
state: Florida
city: Port Orange
country: United States
facility: Accel Research Site - Brain and Spine Institute of Port Orange
state: Florida
city: Tampa
country: United States
facility: USF Parkinson's Disease and Movement Disorders Center
state: Florida
city: Winter Park
country: United States
facility: Charter Research
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research, Inc.
state: Georgia
city: Kansas City
country: United States
facility: Parkinson's Disease and Movement Disorder Center
state: Kansas
city: Roslindale
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Toms River
country: United States
facility: Bio Behavioral Health
state: New Jersey
city: New York
country: United States
facility: New York Neurology Associates
state: New York
city: Raleigh
country: United States
facility: M3 Wake Research
state: North Carolina
city: Columbus
country: United States
facility: Optimed Research Ltd
state: Ohio
city: Dayton
country: United States
facility: Neurology Diagnostics Inc
state: Ohio
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Spokane
country: United States
facility: Inland Northwest Research, LLC
state: Washington
Study officials:
affiliation: Cerevance, Inc.
name: Susan Kapurch
role: STUDY_CHAIR
References: