A Phase 3 Randomized, Double-Blind, Decentralized Clinical Trial to Compare the Efficacy of Celiprolol to Placebo in the Treatment of Patients With COL3A1-Positive Vascular Ehlers-Danlos Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Time to first occurrence of a vEDS-related clinical event requiring medical attention: Fatal/nonfatal cardiac or arterial events [including dissection or rupture], uterine rupture, intestinal rupture, and/or unexplained sudden death
研究概览
简要总结
This is a prospective, Phase 3, randomized, double-blind, placebo-controlled efficacy study to evaluate celiprolol in patients genetically confirmed as COL3A1-positive vEDS using a decentralized clinical trial design.
详细描述
This is a prospective, Phase 3, randomized, double-blind, placebo-controlled efficacy study to evaluate celiprolol in patients genetically confirmed as COL3A1-positive vEDS using a decentralized clinical trial design.
The double-blind portion of this study is intended to end if statistical significance is reached at the interim analysis (accrual of 28 vEDS-related events requiring medical attention; estimated to take 24 months) or after accrual of 46 vEDS related clinical events requiring medical attention (estimated to take 40 months).
A total of approximately 150 patients who meet all the inclusion and none of the exclusion criteria will be enrolled and randomized 2:1 to receive either celiprolol or placebo, respectively.
Following the double-blind treatment period or occurrence of vEDS-related clinical event, patients have the option to participate in an open label extension period.
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)
盲法说明
The patient, the Investigator, and other members of the staff involved with the study will remain blinded to the two study treatments (celiprolol and placebo).
入排标准
- 年龄范围
- 15 Years 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willingness to obtain magnetic resonance angiogram (MRA) image at local imaging facility.
- •A genetic test confirming the presence of a pathogenic COL3A1 variant (classified as likely pathogenic or pathogenic according to ACMG/AMP Guidelines.
- •Patients must be ≥ 15 years of age at the time of randomization.
- •Able and willing to discontinue use of β-blockers prior to randomization.
排除标准
- •Lack of a COL3A1-positive test at screening (e.g., COL3A1 benign, likely benign, variant of unknown significance [VUS] or no variant) or presence of a COL3A1 variant but demonstration of a COL3A1 variant reported to be a haploinsufficiency variant.
- •Arterial rupture or dissection, uterine rupture, and/or intestinal rupture within 6 months prior to Screening.
- •Patients unable to discontinue β-blocker treatment prior to randomization.
- •Unable or unwilling to complete the study procedures.
- •Breastfeeding, pregnancy, or planned pregnancy during the trial.
- •Any medical condition that in the opinion of the Investigator may pose a safety risk to the patient in this study, which may confound efficacy or safety assessment, or may interfere with study participation.
- •Use of any prohibited medications
研究组 & 干预措施
Placebo BID
Placebo twice daily (BID) Placebo given orally to mimic ACER-002 (celiprolol) administration
干预措施: Placebo BID (Drug)
ACER-002 (celiprolol) 200 mg BID
ACER-002 200 mg twice daily (BID) (after titration):
200 mg morning and 200 mg evening: 400 mg total daily dose
Titration:
Day 1 to Month 1 - 100 mg once daily (QD) evening: 100 mg total daily dose Month 2 to Month 3 - 100 mg morning and 100 mg evening: 200 mg total daily dose Month 3 to Month 4 - 100 mg morning and 200 mg evening: 300 mg total daily dose Month 4 to End of Treatment Period (BID) - 200 mg morning and 200 mg evening: 400 mg total daily dose
干预措施: ACER-002 (celiprolol) 200 mg BID (Drug)
结局指标
主要结局
Time to first occurrence of a vEDS-related clinical event requiring medical attention: Fatal/nonfatal cardiac or arterial events [including dissection or rupture], uterine rupture, intestinal rupture, and/or unexplained sudden death
时间窗: Over the double-blind period (estimated to be 40 months)
次要结局
- Number and proportion of patients reporting a vEDS related clinical event requiring medical attention: Fatal/nonfatal cardiac or arterial events [including dissection or rupture], uterine rupture, intestinal rupture, and/or unexplained sudden death(Over the double-blind period (estimated to be 40 months))
- Number and percentage of patients with adverse events(Over the double-blind period (estimated to be 40 months))
- Number and percentage of Serious Adverse Events (SAE)(Over the double-blind period (estimated to be 40 months))
- Number and percentage of patient deaths(Over the double-blind period (estimated to be 40 months))
- Number and percentage of patient discontinuations(Over the double-blind period (estimated to be 40 months))