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

• ClinicalTrials.gov Identifier: NCT04191577
• Recruitment Status: Completed
• First Posted: December 10, 2019
• Last Update Posted: August 8, 2022
• Sponsor: Cerevance Beta, Inc.
• Information provided by (Responsible Party): Cerevance ( Cerevance Beta, Inc. )

Tracking Information

• First Submitted Date: October 30, 2019
• First Posted Date: December 10, 2019
• Last Update Posted Date: August 8, 2022
• Actual Study Start Date: December 2, 2019
• Actual Primary Completion Date: November 6, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 29, 2021)

Number of Subjects who experience Adverse Events related to study drug [ Time Frame: Baseline through 30 days after the last dose ]

AEs with onset or exacerbation up until dosing on Day 1 will be scored as pretreatment events (PTEs), and AEs that occur from first dosing until 30 days after the last dose will be captured as a treatment-emergent AE (TEAE).

Original Primary Outcome Measures (submitted: December 4, 2019)

• Number of Subjects who experience Adverse Events [ Time Frame: Baseline through 30 days after the last dose ]
  AEs with onset or exacerbation up until dosing on Day 1 will be scored as pretreatment events (PTEs), and AEs that occur from first dosing until 30 days after the last dose will be captured as a treatment-emergent AE (TEAE).
• Change from baseline in quantitative 12-lead ECG [ Time Frame: Baseline to Day 27 ]
  Twelve-lead ECGs will be recorded using an ECG machine that automatically calculates the heart rate and measures PR interval, RR interval, QRS interval, QT interval, and QTcF and QTcB (Fridericia's and Bazett's correction method) intervals. Observed values and changes from baseline in quantitative ECG parameters will be summarized by placebo, and each CVN424 dose level.
• Change from baseline in vital sign measurements - Heart Rate [ Time Frame: Baseline to Day 27 ]
  Triplicate orthostatic vital signs (heart rate) will be recorded 15 minutes apart at baseline. Orthostatic vital signs (non-triplicate) will be recorded pre-dose and at 6 h post-dose on Visit Days 1 and 8. Heart rate will be measured after at least 5 minutes supine and (when orthostatic vital signs are specified) and again after 2 minutes standing.
• Clinical Laboratory Assessments - hematology [ Time Frame: Baseline to Day 27 ]
  Individual results of laboratory tests from hematology panels that are abnormal and clinically significant will be summarized and listed. Observed values and change from baseline to post-dose laboratory data will be summarized for placebo, each CVN424 dose level and CVN424 overall. RBC WBC with differential (% and absolute), Hemoglobin, Hematocrit, Platelets, Prothrombin time/INR, Activated partial thromboplastin time (aPTT)
• Weight (kg) [ Time Frame: Baseline to Day 27 ]
  Recorded at screening, baseline, Day 1, and subsequent study visits to determine BMI
• Change from baseline in Questionnaire for Impulsive-Compulsive Disorders (QUIP) [ Time Frame: Baseline through day 27 ]
  Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire to measure observed changes from baseline; scale includes yes/no questions to measure Impulse Control Disorders including questions with gambling, sexual behavior, buying, eating, and any other compulsive behaviors that may be identified by subjects.
• Beck Depression Inventory [ Time Frame: Baseline through day 27 ]
  A 21-item, self-report rating inventory with a scale of 0-3 for severity (0 being symptom is absent, 3 being severe symptoms) that measures characteristic attitudes and symptoms of depression.
• Change from baseline in vital sign measurements - Blood Pressure [ Time Frame: Baseline to Day 27 ]
  Triplicate orthostatic vital signs (blood pressure) will be recorded 15 minutes apart at baseline. Orthostatic vital signs (non-triplicate) will be recorded pre-dose and at 6 h post-dose on Visit Days 1 and 8. Blood pressure will be measured after at least 5 minutes supine and (when orthostatic vital signs are specified) and again after 2 minutes standing.
• Height (m) [ Time Frame: Baseline through day 27 ]
  Recorded at screening, baseline, Day 1, and subsequent study visits to determine BMI
• Clinical Laboratory Assessments - serum chemistry [ Time Frame: Baseline to Day 27 ]
  Individual results of laboratory tests from serum chemistry panels that are abnormal and clinically significant will be summarized and listed. Observed values and change from baseline to post-dose laboratory data will be summarized for placebo, each CVN424 dose level and CVN424 overall. ALT, Albumin, Alkaline phosphatase, AST, Total bilirubin, Direct bilirubin, Total protein, Creatinine, Blood urea nitrogen, Creatine kinase, GGT, Potassium, Sodium, Glucose, Chloride, Bicarbonate, Calcium
• Clinical Laboratory Assessments - urinalysis [ Time Frame: Baseline to Day 27 ]
  Individual results of laboratory tests from urinalysis panels that are abnormal and clinically significant will be summarized and listed. Observed values and change from baseline to post-dose laboratory data will be summarized for placebo, each CVN424 dose level and CVN424 overall. pH, Specific gravity, Protein, Glucose, Blood, Nitrite. Microscopic Analysis (only if positive dipstick results): RBC/high power field WBC/high power field Epithelial cells, casts etc.
• Clinical Laboratory Assessments - endocrine tests [ Time Frame: Baseline to Day 27 ]
  Individual results of laboratory tests from endocrine panels that are abnormal and clinically significant will be summarized and listed. Observed values and change from baseline to post-dose laboratory data will be summarized for placebo, each CVN424 dose level and CVN424 overall. Prolactin, TSH, (and if abnormal) reflex Free T4

Current Secondary Outcome Measures (submitted: July 29, 2021)

• Number of subjects with abnormal and clinically significant (CS) safety laboratory test results, ECG test results, or vital sign measurements [ Time Frame: Baseline through Day 27 ]
  Twelve-lead ECGs will be recorded using an ECG machine that automatically calculates the heart rate and measures PR interval, RR interval, QRS interval, QT interval, and QTcF and QTcB (Fridericia's and Bazett's correction method) intervals. Observed values and changes from baseline in quantitative ECG parameters will be summarized by placebo, and each CVN424 dose level.
• Change from baseline in 2-day average OFF time at Day 27 as recorded in the Patient Motor Diary [ Time Frame: Baseline through Day 27 ]
  Completion of the patient motor diary over the two days prior to each visit.

Original Secondary Outcome Measures (submitted: December 4, 2019)

• Efficacy of CVN424 adjunctive to levodopa [ Time Frame: 30 days prior to randomization through Day 27 ]
  To assess potential efficacy of CVN424 adjunctive to levodopa in alleviating symptoms of PD. Stable is defined as a dosage unchanged in the 30 days prior to randomization and, in the opinion of the investigator, able to continue the current regimen throughout the month-long study without undue inconvenience or harm.)
• PK [ Time Frame: Baseline through day 35 ]
  Concentrations of CVN424 in plasma will be summarized by dose level and by gender (if possible) over each scheduled sampling time using descriptive statistics.

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: December 4, 2019)

• Exploratory RNA [ Time Frame: Pre-dose through 3 hours post dose on Day 1 ]
  To explore possible RNA markers (e.g., drug metabolic enzyme and transporter polymorphisms) that may contribute to variability in CVN424 PK, pharmacodynamics, safety or efficacy
• Exploratory DNA [ Time Frame: Baseline (day 0) ]
  To explore possible DNA markers (e.g., drug metabolic enzyme and transporter polymorphisms) that may contribute to variability in CVN424 PK, pharmacodynamics, safety or efficacy

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Parkinson Disease

Intervention

• Drug: CVN424 Low Dose
  CVN424
• Drug: CVN424 High Dose
  CVN424
• Drug: Placebo
  Placebo

Study Arms

• Placebo Comparator: Placebo
  Placebo to be administered once daily.
  Intervention: Drug: Placebo
• Active Comparator: CVN424 (Low Dose)
  Low dose of CVN424 to be administered once daily.
  Intervention: Drug: CVN424 Low Dose
• Active Comparator: CVN424 (High Dose)
  Patients randomized to the high dose will receive low-dose CVN424 once daily from day 1 to day 7, and will then increase their dose to the full high-dose once daily beginning on day 8.
  Intervention: Drug: CVN424 High Dose

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 4, 2022): 141
• Original Estimated Enrollment (submitted: December 4, 2019): 66
• Actual Study Completion Date: December 13, 2021
• Actual Primary Completion Date: November 6, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04191577
• Other Study ID Numbers: CVN424-201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cerevance ( Cerevance Beta, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: Cerevance Beta, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Susan Kapurch; Cerevance, Inc.

• PRS Account: Cerevance
• Verification Date: August 2022