CardiolRxTM in Recurrent Pericarditis (MAVERIC Phase 3) A Randomized, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 110
- 试验地点
- 41
- 主要终点
- Recurrence of pericarditis
研究概览
简要总结
Multi-center, randomized, double-blind, placebo-controlled, phase-3 Trial. Patients with a history of recurrent pericarditis who are being treated with an IL-1 blocker for at least 12 months, scheduled to be discontinued, will be approached for potential trial participation.
Double-blind treatment will be initiated 10 - 16 days prior to the last scheduled dose of the IL-1 blocker and continued for 24 weeks.
The objective is to assess whether patients remain free of pericarditis recurrence while receiving CardiolRx.
详细描述
Double-blind, randomized, placebo-controlled Phase-3 trial. The primary objective is to assess whether patients remain free of pericarditis recurrence while receiving CardiolRx.
Before any trial-related procedure is performed, written informed consent will be obtained. After informed consent is obtained, patients will be screened for eligibility.
The highest NRS pain score within the past 7 days is to be assessed prior to randomization at Visit 1 (Day 1). Baseline blood samples for central laboratory assessment of hs-CRP and pharmacokinetic assessments should also be collected prior to randomization at Visit 1 (Day 1).
All other screening assessments will be performed at any time within 7 days prior to randomization at Visit 1 (Day 1) and include the following: Physical examination, vital signs, 12-lead ECG; C-SSRS and blood draws for local laboratory assessments (see Section 17.2).
Eligible patients will be randomized at Visit 1 (Day 1) to either CardiolRx or matching placebo in a 1:1 ratio. Double-blind trial therapy will be initiated in the evening of Day 1, 10 - 16 days (no additional time window is allowed) prior to the last scheduled dose of the IL-1 blocker and after all baseline assessments are completed. Trial therapy will be administered for 24 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
double-blind, placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 18 years of age or older
- •A history of recurrent pericarditis with stable disease and currently being treated with an IL-1 blocker, scheduled to be discontinued. Stable disease is defined as:
- •treatment with an IL-1 blocker for at least 12 months,
- •free of pericarditis recurrence for at least 6 months and this recurrence, if present, must have occurred in the setting of an interruption or tapering of an IL-1 blocker; and
- •treatment with an unchanged dose and regimen of on an IL-1 blocker for at least 3 months prior to randomization.
- •Pericarditis pain les or equal than 2 on the 11-point Numerical Rating Scale (NRS) for at least 7 days prior to randomization (Visit 1, Day 1)
- •C-Reactive Protein (CRP) < 1.0 mg/dL during screening within 7 days prior to randomization (Visit 1, Day 1).
- •Patients who have had a vasectomy or who are willing to use double barrier contraception methods with partners of childbearing potential during the conduct of the trial and for 2 months after the last dose of trial therapy.
- •Patients of childbearing potential willing to use an acceptable method of contraception starting with trial therapy administration and for a minimum of 2 months after trial completion. Otherwise, these patients must be postmenopausal (at least 1 year absence of vaginal bleeding or spotting and confirmed by follicle stimulating hormone [FSH] ≥ 40 mIU/mL [or ≥ 40 IU/L] if less than 2 years postmenopausal) or be surgically sterile.
- •Acceptable birth control methods that result in a failure rate of less than 1 % include oral, intravaginal or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); using double-barrier contraception methods with their partners; bilateral tubal occlusion; vasectomised partner; sexual abstinence.
排除标准
- •Pericarditis recurrence(s) during IL-1 blocker treatment without interruption or tapering of the IL-1 blocker
- •Diagnosis of pericarditis that is secondary to specific prohibited etiologies, including tuberculosis (TB); neoplastic, purulent, or radiation etiologies; post-thoracic blunt trauma (e.g., motor vehicle accident); systemic autoimmune disease (e.g., systemic lupus erythematosus)
- •Primary diagnosis of myocarditis (diagnosis of myopericarditis is accepted)
- •Estimated glomerular filtration rate (eGFR) < 30 mL/min during screening within 7 days prior to randomization (Visit 1, Day 1)
- •Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limit of normal (ULN) or ALT or AST > 3x ULN plus bilirubin > 2x ULN during screening within 7 days prior to randomization (Visit 1, Day 1).
- •Sepsis, defined as documented bacteremia during screening within 7 days prior to randomization (Visit 1, Day 1) or other untreated or uncontrolled bacterial infection*
- •Prior history of sustained ventricular arrhythmia(s)
- •History of diagnosed long QT syndrome
- •QTc interval > 480 msec (biologically female) or > 470 msec (biologically male) (please refer to Section 9.2.3 for bundle branch block, bifascicular block and paced rhythm correction) or second or third degree atrioventricular (AV) block in a patient without an implanted functioning pacemaker device during screening within 7 days prior to randomization (Visit 1, Day 1)
- •Showing suicidal tendency during the last 12 months, as defined by answering "yes" to question 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS), administered during screening within 7 days prior to randomization (Visit 1, Day 1)
- •Participation in a clinical trial in which an investigational drug or device was administered within 30 days of screening or within 5 half-lives of the previous study drug, whichever is longer
- •Inability or unwillingness to give informed consent
- •Ongoing drug or alcohol abuse in the opinion of the investigator
- •On any cannabinoid during the past month or unwilling to stay abstinent from all cannabis products for the duration of the trial
- •Pregnant or breastfeeding
- •Current diagnosis of active cancer, with the exception of non-melanoma skin cancer
- •Any factor, which would make it unlikely that the patient can comply with the trial procedures
- •Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment
- •Has received systemic immunomodulatory agents as below prior to randomization:
- •Methotrexate (within 2 weeks)
- •Azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, or mercaptopurine (within 24 weeks)
- •Canakinumab, TNF inhibitors, IL-6 inhibitors, or janus-activating kinase inhibitors (within 12 weeks)
- •Intravenous immune globulin (IVIG) (within 8 weeks)
- •Corticosteroids (within 4 weeks)
- •Known hypersensitivity to the active substance or any of the excipients of the trial
研究组 & 干预措施
Placebo
- Initial starting dose (Day 1, evening dose to Day 3, morning dose):
5 mg/kg of body weight matching placebo b.i.d.
- Day 3, evening dose to Day 10, morning dose: 7.5 mg/kg of body weight matching placebo b.i.d.
- Day 10, evening dose to morning dose of the Week 24 Visit:
10 mg/kg of body weight matching placebo b.i.d.
干预措施: CardiolRx (Drug)
CardiolRx
- Initial starting dose (Day 1, evening dose to Day 3, morning dose):
5 mg/kg of body weight CardiolRx b.i.d.
- Day 3, evening dose to Day 10, morning dose: 7.5 mg/kg of body weight CardiolRx b.i.d.
- Day 10, evening dose to morning dose of the Week 24 Visit:
10 mg/kg of body weight CardiolRx b.i.d.
干预措施: CardiolRx (Drug)
结局指标
主要结局
Recurrence of pericarditis
时间窗: 24 weeks
proportions of patients free from a new episode of recurrent pericarditis\* from the timepoint of stopping the IL-1 blocker to Week 24
time to pericarditis recurrence
时间窗: 24 weeks
time to a new episode of recurrent pericarditis\* from the timepoint of stopping the IL-1 blocker to Week 24
次要结局
- Proportions of patients free from a new episode of recurrent pericarditis(24 weeks)
- Percentage of days with no or minimal pain(24 weeks)