Phase 2b Randomized, Double-blind, Placebo-controlled Crossover Study Evaluating the Efficacy and Safety of Zagociguat in Participants With MELAS (PRIZM)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 20
- 主要终点
- • PROMIS Fatigue MELAS Short Form scores• Groton Maze Learning Test scores • International Digit Symbol Substitution Test scores
研究概览
简要总结
PRIZM is a Phase 2b randomized, double-blind, placebo-controlled, 3-treatment, 2-period, crossover study evaluating the efficacy and safety of oral zagociguat 15 and 30 mg vs. placebo when administered daily for 12 weeks in participants with genetically and phenotypically defined MELAS.
详细描述
The goal of this clinical trial is to learn about the effectiveness of zagociguat in patients with MELAS. The main questions it aims to answer are:
- Does zagociguat improve fatigue in patients with MELAS?
- Does zagociguat improve cognitive performance in patients with MELAS?
- What is the safety and tolerability profile of zagociguat?
The PRIZM study is evaluating 2 dose levels of zagociguat in a crossover design consisting of two 12-week treatment periods separated by a 4-week washout. Patients will be screened and if eligible, randomly assigned either to receive placebo in period 1 followed by active drug in period 2 OR to receive active drug in period 1 followed by placebo in period 2. Study medication is a once daily oral tablet and will be provided at the clinic and/or shipped to the participant's home. Clinic visits will occur at screening and Week 1 and Week 12 of each treatment period. Visits at Week 4 and Week 8 of both crossover periods will either be in clinic or optionally at the participant's home. Study assessments will be conducted weekly on a phone app and a separate tablet and additional assessments will be conducted during visits. Patients who complete the study will be eligible for an open label extension study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This a double-blind study in which investigators, participants/caregivers, Sponsor, and all study personnel will be blinded.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed consent form.
- •18 to 75 years of age.
- •Diagnosed with MELAS based on the presence of each of the following criteria:
- •A documented pathogenic variant in a mitochondrial DNA (mtDNA) gene.
- •History of one or more stroke-like episodes (SLEs) with magnetic resonance imaging (MRI) findings consistent with stroke-like lesions.
- •Scores below normal average on the iDSST and GMLT.
- •Reports fatigue due to MELAS.
- •Can complete at least 1 sit-to-stand in the 30-second test interval.
- •Completes all at-home weekly activities independently during the Screening Period (caregiver may help set up device/app, log-in, etc.).
- •Other criteria per the protocol.
排除标准
- •Systolic blood pressure (BP) 90 mmHg or diastolic BP 60 mmHg.
- •Orthostatic hypotension when measured after standing from a semi-recumbent/supine position.
- •Active cancer significant enough to confound the results of this study.
- •Severe gastrointestinal dysmotility that may impact participation.
- •Recent history (within last 6 months) of platelet dysfunction, hemophilia, von Willebrand disease, coagulation disorder, other bleeding diathesis condition(s), or significant, nontraumatic bleeding episodes.
- •History of spontaneous fracture(s) that in the investigator's opinion represents a safety risk for trial participation.
- •Current use of prohibited medication (reviewed by investigator).
- •Any medical or other condition that the investigator thinks would preclude study participation.
- •Other exclusion criteria per protocol.
研究组 & 干预措施
Placebo then Zagociguat 15mg
Participants first receive placebo once a day for 12 weeks. Then after a 4 week washout, they receive zagociguat 15 mg once a day for 12 weeks.
干预措施: zagociguat 15mg (Drug)
Placebo then Zagociguat 15mg
Participants first receive placebo once a day for 12 weeks. Then after a 4 week washout, they receive zagociguat 15 mg once a day for 12 weeks.
干预措施: Placebo (Drug)
Zagociguat 15mg then Placebo
Participants first receive zagociguat 15 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks.
干预措施: zagociguat 15mg (Drug)
Zagociguat 15mg then Placebo
Participants first receive zagociguat 15 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks.
干预措施: Placebo (Drug)
Placebo then Zagociguat 30mg
Participants first receive placebo once a day for 12 weeks. Then after a 4-week washout, they receive zagociguat 30 mg once a day for 12 weeks.
干预措施: zagociguat 30mg (Drug)
Zagociguat 30mg then Placebo
Participants first receive zagociguat 30 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks.
干预措施: zagociguat 30mg (Drug)
Placebo then Zagociguat 30mg
Participants first receive placebo once a day for 12 weeks. Then after a 4-week washout, they receive zagociguat 30 mg once a day for 12 weeks.
干预措施: Placebo (Drug)
Zagociguat 30mg then Placebo
Participants first receive zagociguat 30 mg once a day for 12 weeks. Then after a 4-week washout, they receive placebo once a day for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
• PROMIS Fatigue MELAS Short Form scores• Groton Maze Learning Test scores • International Digit Symbol Substitution Test scores
时间窗: Weeks 9 through 12 of each treatment period
These measures are a patient reported questionnaire on MELAS-specific fatigue and 2 cognitive performance tests. These 3 outcome measures will be combined using a global statistical test.
• PROMIS Fatigue MELAS Short Form scores• Groton Maze Learning Test scores • International Digit Symbol Substitution Test scores
时间窗: Weeks 9 through 12 of each treatment period
These measures are a patient reported questionnaire on MELAS-specific fatigue and 2 cognitive performance tests. These 3 outcome measures will be combined using a global statistical test.
Incidence of Treatment-emergent Adverse Events (TEAEs)
时间窗: Weeks 1 through washout for treatment period 1 and Weeks 1 through follow-up for treatment period 2
TEAEs are any untoward event that may or may not be related to study medication.
次要结局
- Number of repetitions completed during the 30-second sit-to-stand test(Week 12)
- PROMIS Cognitive Function MELAS Short Form (PCFM-SF) score(Week 12)
- Plasma concentrations of GDF-15(Week 12)
- Memory composite scores (One Card Learning and One Back Tests) for Week 9 through 12(Week 9 through 12)