Trial Outcomes & Findings for Study of CVN424 in Parkinson's Disease Patients With Motor Fluctuations (NCT NCT04191577)

NCT ID: NCT04191577

Last Updated: 2024-07-03

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

136 participants

Primary outcome timeframe

Up to Day 35

Results posted on

2024-07-03

Participant Flow

21 study sites in the United States

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	44	45	47
Overall Study COMPLETED	41	42	44
Overall Study NOT COMPLETED	3	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Withdrawal by Subject	2	2	1
Overall Study Physician Decision	1	1	0
Overall Study Adverse Event	0	0	1
Overall Study Death	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Arm n=44 Participants 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.	CVN424 50 mg n=45 Participants 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.	CVN424 150 mg n=47 Participants 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.	Total n=136 Participants Total of all reporting groups
Age, Continuous	67.0 years STANDARD_DEVIATION 7.10 • n=5 Participants	63.0 years STANDARD_DEVIATION 7.67 • n=7 Participants	65.6 years STANDARD_DEVIATION 9.05 • n=5 Participants	65.2 years STANDARD_DEVIATION 8.12 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants	42 Participants n=4 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	33 Participants n=7 Participants	27 Participants n=5 Participants	94 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	41 Participants n=7 Participants	46 Participants n=5 Participants	129 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to Day 35

Population: Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Placebo Arm n=44 Participants 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.	CVN424 50 mg n=45 Participants 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.	CVN424 150 mg n=47 Participants 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.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Study Drug	9.1 Percentage of participants	17.8 Percentage of participants	19.1 Percentage of participants

SECONDARY outcome

Timeframe: Up to Day 35

Population: Safety Analysis Set

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.

Outcome measures

Outcome measures
Measure	Placebo Arm n=44 Participants 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.	CVN424 50 mg n=45 Participants 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.	CVN424 150 mg n=47 Participants 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.
Percentage of Participants With Clinically Significant Abnormal Laboratory Parameters	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Day 35

Population: Safety Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Placebo Arm n=44 Participants 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.	CVN424 50 mg n=45 Participants 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.	CVN424 150 mg n=47 Participants 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.
Percentage of Participants With Clinically Significant Changes 12-Lead Electrocardiogram (ECG) Findings	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Day 35

Population: Safety Analysis Set.

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.

Outcome measures

Outcome measures
Measure	Placebo Arm n=44 Participants 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.	CVN424 50 mg n=45 Participants 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.	CVN424 150 mg n=47 Participants 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.
Percentage of Participants With Clinically Significant Abnormal Vital Signs	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and at Day 27

Population: Primary Efficacy Analysis Set comprised of all participants who were eligible, randomized, and received at least one dose of study drug, classified according to the treatment actually received. Only those participants with data available at specified timepoints has been presented.

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.

Outcome measures

Outcome measures
Measure	Placebo Arm n=39 Participants 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.	CVN424 50 mg n=38 Participants 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.	CVN424 150 mg n=44 Participants 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.
Change From Baseline in 2-day Average OFF Time	-0.462 Hours Standard Deviation 2.9265	-1.342 Hours Standard Deviation 2.9680	-1.563 Hours Standard Deviation 2.5261

Adverse Events

Placebo Arm

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

CVN424 50 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

CVN424 150 mg

Serious events: 1 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Arm n=44 participants at risk 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.	CVN424 50 mg n=45 participants at risk 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.	CVN424 150 mg n=47 participants at risk 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.
Cardiac disorders cardiac arrest	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Number of events 1 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.

Other adverse events

Additional Information

Michelle Charles, Executive Director Regulatory Affairs

Cerevance

Phone: (408) 220-5722

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo Arm n=44 participants at risk 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.	CVN424 50 mg n=45 participants at risk 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.	CVN424 150 mg n=47 participants at risk 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.
Gastrointestinal disorders Nausea	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	4.4% 2/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	4.3% 2/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Nervous system disorders Headache	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	4.3% 2/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Cardiac disorders Tachycardia	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	4.4% 2/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Gastrointestinal disorders Vomiting	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	4.3% 2/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Blood and lymphatic system disorders Leukopenia	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Gastrointestinal disorders Abdominal distension	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.2% 1/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Gastrointestinal disorders Constipation	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Gastrointestinal disorders Dry mouth	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
General disorders Fatigue	2.3% 1/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
General disorders Pyrexia	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Infections and infestations Oral herpes	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.2% 1/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Investigations Blood creatine phosphokinase increased	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.2% 1/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Investigations Blood pressure increased	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.2% 1/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Investigations Gamma-glutamyl transferase increased	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.2% 1/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Musculoskeletal and connective tissue disorders Muscle fatigue	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.2% 1/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Nervous system disorders Dizziness	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Nervous system disorders Dizziness postural	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.2% 1/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Nervous system disorders Dyskinesia	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Nervous system disorders Tremor	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Psychiatric disorders Anxiety	2.3% 1/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.2% 1/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Psychiatric disorders Behaviour disorder	2.3% 1/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Psychiatric disorders Hallucination	2.3% 1/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Psychiatric disorders Nightmare	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.
Vascular disorders Orthostatic hypotension	0.00% 0/44 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	0.00% 0/45 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.	2.1% 1/47 • Up to Day 35 TEAEs has been collected in Safety Analysis Set.