NCT06553027进行中（未招募）3 期
Phase 3, Randomized, Double-Blind, Placebo-Controlled Multicenter Study of CVN424 in Parkinson's Disease Patients With Motor Complications
Cerevance112 个研究点 分布在 2 个国家目标入组 330 人开始时间: 2024年9月20日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 330
- 试验地点
- 112
- 主要终点
- Change from Baseline to Week 12 in average daily OFF time on motor diaries for 150 mg CVN424 compared to placebo
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, multicenter study in participants with Parkinson's disease (PD) with motor fluctuations. Participants will be randomized to receive once-daily oral doses of either 75 milligrams (mg) CVN424 or 150 mg CVN424, or a matching placebo for 12 weeks. Participants who successfully complete this study and retain eligibility/suitability will be invited to participate in a future open-label extension (OLE) study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of PD consistent with United Kingdom (UK) Brain Bank criteria and MDS Research Criteria for the Diagnosis of PD; must include bradykinesia with sequence effect and motor asymmetry if no rest tremor, and a prominent response to levodopa.
- •Body Mass Index (BMI) > 18.0 and < 35.0 Kilograms per meter square (kg/m^2), inclusive at Screening.
- •Modified Hoehn and Yahr Stage ≤ 3 in the ON state.
- •Freely ambulatory at the time of Screening (with/without assistive device).
- •Montreal Cognitive Assessment (MoCA) Score of at least
- •PD medications must be stable for at least 4 weeks prior to Screening; monoamine oxidase B (MAO-B) inhibitors must be stable for at least 12 weeks prior to Screening.
- •Levodopa administration at least 4 times daily (immediate or extended release) or three times daily (Rytary or Crexont).
- •Stable use of oral anti-sialorrhea medications for 30 days before Screening, without anticipated need for change during the study.
- •Average of ≥ 3 h total OFF time/day on Screening home diaries, with at least 2.5 hours OFF on each diary day.
- •During Screening, capable of adequately identifying ON, OFF, and dyskinetic states (>80% concordance) through properly completed ON/OFF diaries.
- •Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and for at least 12 weeks after the last dose of study drug has been taken.
- •Able and willing to give written informed consent approved by an institutional review board, and to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.
- •Approved as an appropriate and suitable candidate by the Enrollment Authorization Committee (EAC)
排除标准
- •Diagnosis of secondary or atypical parkinsonism.
- •Severe or disabling dyskinesias or OFF expected to preclude successful study participation, in the opinion of the investigator.
- •Any previous procedure or therapy designed to provide continuous levodopa or stimulation of dopaminergic tone (i.e., Duopa, apomorphine, subcutaneous levodopa), surgery for PD (i.e., deep brain stimulation [DBS]), or anticipation of these during the study.
- •History of exclusively diphasic, OFF state, myoclonic or dystonic dyskinesias without peak-dose choreiform dyskinesia.
- •Clinically significant orthostatic hypotension (consistently symptomatic or requires medication).
- •Clinically significant hallucinations requiring antipsychotic use.
- •Current use of strong CYP3A4/5 inhibitors or inducers.
- •Routine use of PD on-demand medications (i.e., inhaled levodopa, apomorphine injection). Routine use defined as three (3) or more uses per week of on-demand medication is not allowed. On demand medications should only be used for medical emergencies and should be avoided on anticipated diary days, as best as possible.
- •Use of injectable botulinum medication for sialorrhea within 90 days of screening or during the study.
- •Current use of medication with dopamine antagonist activity, or any use within 12 months of Screening.
- •Clinically significant medical, surgical, psychiatric, or laboratory abnormalities that in the judgment of the investigator would preclude adequate participation or completion of the study.
- •Clinically significant ECG abnormalities at Screening.
- •Prolonged Fridericia-corrected QT (QTcF) interval on ECG at Screening.
- •Clinically significant heart disease within 2 years of Screening, defined as follows:
- •Significant cardiac event within 12 weeks prior to Screening (e.g., admission for myocardial infarction, unstable angina, or decompensated heart failure), angina pectoris or episode of congestive heart failure with symptoms > grade 2 New York Heart Association classification, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia.
- •History of complex arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment.
- •Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
- •Symptomatic bradycardia, sick sinus syndrome or atrioventricular block greater than first degree in the absence of a pacemaker
- •Unexplained syncope
- •Brugada syndrome
- •Hypertrophic cardiomyopathy
- •Any clinically significant history of malignancy or ongoing malignancy of sufficient concern for interference with completion of the study or quality of study experience, in the opinion of the investigator and medical monitor.
- •Active major depressive disorder or a Beck Depression Inventory-II (BDI-II) score of >
- •Has active suicidal ideation within one year prior to Screening as determined by the C-SSRS or attempted suicide within the last 5 years.
- •Has been diagnosed with or history of a substance-related disorder (excluding nicotine and caffeine), including alcohol-related disorder by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria, during the 12 months prior to Screening.
- •Tests positive at Screening for drugs of abuse. Drugs of abuse refers to illicit substances and does not include participants taking physician-prescribed medications. For participants who are legally prescribed cannabis for medical reasons, the appropriateness of the participant for this study will be made by the judgement of the Investigator in consultation with the Medical monitor.
- •Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN) or a degree of hepatic impairment using the Child-Pugh classification of B or C.
- •Significant renal impairment as determined by estimated glomerular filtration rate (eGFR) less than or equal to 60 milliliters per minute (ml/min).
- •Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCV) antibody, or Human Immunodeficiency Virus (HIV) infection at Screening.
- •Currently lactating or pregnant or planning to become pregnant during the study.
- •Previous exposure to CVN
- •Currently participating in or has participated in another study of an investigational medicinal product (IMP) or medical device in the last 3 months or within 5 half-lives of the IMP (whichever is longer) prior to Screening.
- •A known hypersensitivity to the IMP or to any excipients used in the formulation.
研究组 & 干预措施
CVN424 75 mg
Experimental
Participants will be administered with oral doses of 75 mg CVN424.
干预措施: CVN424 75 mg (Drug)
CVN424 150 mg
Experimental
Participants will be administered with oral doses of 150 mg CVN424.
干预措施: CVN424 150 mg (Drug)
Placebo
Placebo Comparator
Participants will be administered with placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from Baseline to Week 12 in average daily OFF time on motor diaries for 150 mg CVN424 compared to placebo
时间窗: Baseline and Up to Week 12
The assessment of the average daily OFF time, normalized to waking hours will be based on diaries completed at home for three consecutive days during the 7-day period before a scheduled in-person visit.
次要结局
- Change from Baseline to Week 12 in the ON time without troublesome dyskinesia(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Clinical Global Impression Scale - Severity (CGI-S)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Epworth Sleepiness Scale (ESS)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Patient Global Impression Scale - Severity (PGI-S)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the MDS-UPDRS Part III(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Parkinson's Disease Questionnaire-39 (PDQ-39)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 in the ON time with no dyskinesia(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the MDS-UPDRS Part I(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Starkstein Apathy Scale (SAS)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the CogState digital cognitive battery(Baseline and Up to Week 12)
- Number of participants with suicidal ideation as measured by Columbia Suicide Severity Rating Scale (C-SSRS)(Up to Week 12)
- Number of participants with clinically significant changes in physical examination, vital signs, electrocardiogram (ECG) finding, and laboratory values(Up to Week 14)
- Percentage of completers(Up to Week 12)
- Change from Baseline to Week 12 on the Schwab and England (S & E) Activities of Daily Living Scale (ADL)(Baseline and Up to Week 12)
- Number of participants reporting treatment emergent adverse events (TEAEs), TEAEs related to moderate or severe intensity and leading to withdrawal of study drug(Up to Week 14)
- Number of participants reporting serious adverse events (SAEs)(Up to Week 14)
- Number of participants with impulse control disorders as measured by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson 's disease Rating Scale (QUIP-RS)(Up to Week 12)
- Change from Baseline to Week 12 on the MDS-UPDRS Part III(Baseline and Up to Week 12)
- Change from Baseline to Week 12 in the ON time without troublesome dyskinesia(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Clinical Global Impression Scale - Severity (CGI-S)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Patient Global Impression Scale - Severity (PGI-S)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Epworth Sleepiness Scale (ESS)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 in the ON time with no dyskinesia(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the MDS-UPDRS Part I(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the Parkinson's Disease Questionnaire-39 (PDQ-39)(Baseline and Up to Week 12)
- Change from Baseline to Week 12 on the CogState digital cognitive battery(Baseline and Up to Week 12)
- Number of participants reporting treatment emergent adverse events (TEAEs), TEAEs related to moderate or severe intensity and leading to withdrawal of study drug(Up to Week 14)
- Number of participants reporting serious adverse events (SAEs)(Up to Week 14)
- Number of participants with suicidal ideation as measured by Columbia Suicide Severity Rating Scale (C-SSRS)(Up to Week 12)
- Number of participants with impulse control disorders as measured by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson 's disease Rating Scale (QUIP-RS)(Up to Week 12)
- Number of participants with clinically significant changes in physical examination, vital signs, electrocardiogram (ECG) finding, and laboratory values(Up to Week 14)
- Percentage of completers(Up to Week 12)
研究者
研究点 (112)
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• Despite missing the primary endpoint, solengepras demonstrated promising trends in improving non-motor symptoms and functional impairments, with fewer adverse events related to non-motor symptoms reported in the treatment arm.
• The company is advancing solengepras in the pivotal Phase III ARISE trial as an adjunctive therapy to levodopa for Parkinson's patients with motor fluctuations, with topline data expected in the first half of 2026.last yearSolengepras Enters Phase 3 for Parkinson's, SAGE-718 Discontinued, and Neurogene Pauses NGN-401 High-Dose Trial• Cerevance's solengepras (CVN424) has entered a Phase 3 trial (ARISE) as an adjunctive therapy for Parkinson's disease, with topline data expected in the first half of 2026.
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• The ARISE trial (NCT06553027) will evaluate solengepras' efficacy in reducing off-time in Parkinson's patients already treated with levodopa.
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• Topline data from the ARISE trial is expected in the first half of 2026, with a focus on changes in daily off-time after 12 weeks of treatment.last yearCerevance's Solengepras Enters Phase 3 Trial for Parkinson's Disease• Cerevance's solengepras (CVN424) has entered a Phase 3 trial (ARISE) as an adjunctive therapy for Parkinson's disease, targeting the GPR6 receptor.
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• Phase 2 data showed solengepras significantly reduced OFF time compared to placebo, with trends toward increased ON time without troublesome dyskinesia.last year
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