A Two-Part Study of REC-994 in the Treatment of Adults With Symptomatic Cerebral Cavernous Malformation (CCM); Part 1: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Two Doses of REC-994; Part 2: A Long-Term Blinded Extension Clinical Trial to Evaluate Long-Term Safety Tolerability and Efficacy of REC-994
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 29
- 主要终点
- Incidence and severity of adverse events (AEs)
研究概览
简要总结
This is a two-part, multi-center, randomized, double-blind, placebo-controlled study to investigate the safety, efficacy and pharmacokinetics of REC-994 (200 mg and 400 mg) compared to placebo in participants with symptomatic cerebral cavernous malformation (CCM).
详细描述
Part 1: Participants will receive treatment over a period of 12 months. Part 2: Optional long-term extension (LTE) for participants completing Part 1 and who are eligible for extended treatment with REC-994.
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
- Triple (Participant, Care Provider, Investigator)
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
- •18 years of age or older with anatomic CCM lesions demonstrated by brain MRI
- •Have symptomatic CCM
- •Have provided written informed consent to participate in the study
- •Have not participated in a clinical trial utilizing an investigational agent within 28 days or within 5 half-lives of the investigational drug (whichever is longer) prior to Screening
排除标准
- •Symptoms deemed by the study Investigator to be caused exclusively by irreversible neuronal damage from prior stroke or neurosurgical instrumentation
- •History of cranial irradiation or surgical/radiosurgical treatment of the primary symptomatic CCM lesion
- •Pregnant or breast feeding
- •Be unable or unwilling to participate in MRI assessments (e.g., claustrophobia, metal implant or implanted cardiac pacemaker)
- •Liver dysfunction or active liver disease as defined by baseline serum transaminases >2x upper limit of normal (ULN)
- •Have moderately or severely impaired renal function (estimated glomerular filtration rate [eGFR] <60ml/min) or active renal disease or have previously received a kidney transplant
- •Have had a previous diagnosis of skeletal muscle disorders (myopathy) of any cause or have a baseline creatine kinase level > 5x ULN
- •History of alcohol or substance abuse within 1 year prior to screening
- •Clinically significant laboratory abnormality
- •Have had an intracerebral hemorrhage within 3 months of screening or any brain surgery within 6 months of screening (not including the primary symptomatic CCM lesion)
研究组 & 干预措施
REC-994 200 mg
REC-994 200 mg po once daily (QD) (1 200 mg REC-994 tablet, 1 matching placebo tablet)
干预措施: Placebo (Drug)
Placebo
Matching Placebo po QD (2 matching placebo tablets)
干预措施: Placebo (Drug)
REC-994 200 mg
REC-994 200 mg po once daily (QD) (1 200 mg REC-994 tablet, 1 matching placebo tablet)
干预措施: REC-994 (Drug)
REC-994 400 mg
REC-994 400 mg po QD (2 200 mg REC-994 tablets)
干预措施: REC-994 (Drug)
结局指标
主要结局
Incidence and severity of adverse events (AEs)
时间窗: Up to 24 months
次要结局
- Change in patient reported outcomes (Cerebral Cavernous Malformation Health Index)(Up to 24 months)
- Change in patient reported outcomes (Modified Rankin Scale)(Up to 24 months)
- Change in patient reported outcomes (SymptoMScreen Score)(Up to 24 months)
- Change in disease-associated symptoms (number of MRI-confirmed cerebral hemorrhagic events)(Up to 24 months)
- Plasma concentrations of REC-994(Up to 12 months)