Phase 1/2 Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending-Dose Clinical Study for the Safety, Tolerability, and Efficacy of IV MTP-131 for Mitochondrial Myopathy in Genetically Confirmed Mitochondrial Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 4
- 主要终点
- Change in Distance Walked (Meters) on the 6-minute Walk Test (6MWT)
研究概览
简要总结
Phase 1/2, multi-center, randomized, double-blind, multiple ascending dose, placebo-controlled study that enrolled 36 subjects with mitochondrial myopathy associated with genetically confirmed mitochondrial disease to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MTP-131 in this patient population.
详细描述
This multi-center, randomized, double-blind, placebo-controlled study enrolled 36 subjects into 3 cohorts of 12 subjects each to evaluate treatment with 3 ascending doses of intravenous elamipretide (0.01, 0.10, and 0.25 mg/kg/hr infused for 2 hours). After each cohort, a Safety Monitoring Board (SMB) determined if dose escalation to the next higher dose of elamipretide was warranted. Each cohort went through 3 distinct periods: Screening, Treatment, and Follow-up.
The Screening Period started with informed consent and may have lasted up to 40 days. During this period, screening procedures to determine subject eligibility for the study occurred, including confirmation of disease, which incorporated a committee review of the investigator-submitted diagnosis and genetic results. The Treatment Period began on Day 1 (Visit 2) and lasted for 5 days (until Day 5 [Visit 6]). Within each cohort, 9 subjects were randomized to active drug and 3 subjects were randomized to placebo on Day 1 and subjects received treatment once a day for 5 consecutive days. Safety, tolerability, and efficacy measures were performed at pre-specified times. The Follow-up Period began at the time of discharge on Day 5. Subjects returned to the study center for the Follow-up Visit on Day 7 (+1 day).
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
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of mitochondrial disease believed to impair the mitochondrial respiratory chain.
- •Eligibility requires prior genetic confirmation of mitochondrial disease.
- •Diagnosis of mitochondrial myopathy judged by the Investigators to be due to existing mitochondrial disease.
- •Must be able to complete a Screening Visit 6MWT.
- •Body mass index (BMI) score >15.0 and <35.0 kg/m2 at Screening Visit.
- •Women of childbearing potential must agree to use birth control as specified in the protocol from the date they sign the ICF until two months after the last dose of study drug.
排除标准
- •Any prior or current medical condition that, in the judgment of the Investigator, would prevent the subject from safely participating in and/or completing all study requirements.
- •Had any exclusionary Newcastle Mitochondrial Disease Adult Scale (NMDAS) scores at Screening Visit.
- •Hospitalized (admitted as in-patient) within 1 month prior to the Baseline Visit.
- •A history of type 1 diabetes mellitus (T1DM).
- •Uncontrolled Type 1 (T1DM) or Type 2 diabetes mellitus (T2DM), in the opinion of the investigator.
- •A creatinine clearance <45 mL/min as calculated by the Cockcroft Gault equation.
- •Requires pacemaker, defibrillator, or has undergone cardiac surgery within 2 years of Screening Visit.
- •QTc elongation defined as a QTc >450 msec in male subjects and >480 msec in female subjects.
- •Uncontrolled hypertension (>160 mmHg systolic or >100 mmHg diastolic) at Screening Visit.
- •History of rhabdomyolysis defined as an acute rise in the serum creatine phosphokinase (CPK) value that, in the opinion of the investigator, caused clinically significant symptoms.
- •Serum sodium more than 5 meq/L below the reference lower limit of normal at Screening Visit.
- •Participated in another interventional clinical trial within 3 months of the screening visit or is currently enrolled in a non-interventional clinical trial judged by the Investigator to be incompatible with the current trial.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Low Dose
elamipretide 0.01 mg/kg/hr infused for 2 hours for 5 days
干预措施: elamipretide (low dose) (Drug)
Intermediate dose
elamipretide 0.10 mg/kg/hr infused for 2 hours for 5 days
干预措施: elamipretide (intermediate dose) (Drug)
High dose
elamipretide 0.25 mg/kg/hr infused for 2 hours for 5 days
干预措施: elamipretide (high dose) (Drug)
Placebo
In each cohort, subjects received either IV elamipretide given once daily for 2 hours for 5 days or matching placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Distance Walked (Meters) on the 6-minute Walk Test (6MWT)
时间窗: Assessed at Baseline, Day 5 (end-of-treatment visit)
Change in distance walked as measured by meters on the 6-minute walk test from baseline (last assessment prior to start of study) to Day 5 (end of treatment visit).
次要结局
- Change in Maximum Oxygen Uptake (ml/kg/Min)(Baseline, Day 5)
- Change in Ventilatory Efficiency (VE/VCO2 Slope)(Baseline, Day 5)
- Change in Aerobic Efficiency (ΔO2 Consumption/Δ Work Ratio)(Baseline, Day 5)
- Change in Oxygen Utilization (ΔVO2/ΔlogVE Ratio)(Baseline, Day 5)
- Change in Oxygen Uptake Kinetics (Mean Response Time as Measured by Seconds)(Baseline, Day 5)
- Change in Pre-exercise Lactate Levels (mg/dL)(Baseline, Day 5)
- Change in Post-exercise Lactate Levels (mg/dL)(Baseline, Day 5)
- Change in Peak Respiratory Exchange Ratio (VCO2/VO2)(Baseline, Day 5)
- Change in Peak Respiratory Rate (Breaths/Min)(Baseline, Day 5)
- Change in Peak Ventilation (L/Min)(Baseline, Day 5)
- Change in Peak Heart Rate (Beats/Min)(Baseline, Day 5)
- Change in Peak Oxygen Saturation (% O2-saturated Hemoglobin)(Baseline, Day 5)
- Change in Peak Systolic Blood Pressure (mmHg)(Baseline, Day 5)
- Change in Peak Diastolic Blood Pressure (mmHg)(Baseline, Day 5)
- Change in Peak Borg Dyspnea(Baseline, Day 5)
- Change in VO2 Anaerobic Threshold (mL)(Baseline, Day 5)
- Change in Watts(Baseline, Day 5)
- Change in Temperature (°C)(Baseline, Day 5)
- Change in ECG-PR Interval (Msec)(Baseline, Day 5)
- Number of Participants Who Had Suicide Ideation, Suicidal Behavior, or Non-suicidal Self-injurious Behavior Post-screening.(Days 1-5 and Day 7.)
- Change in Creatine Phosphokinase (IU/L)(Baseline, Day 5)
- Change in Alanine Aminotransferase (ALT) (U/L)(Baseline, Day 5)
- Change in Eosinophils (10^9 Cells/L)(Baseline, Day 5)
- Change in ECG-QRS Complex (Msec)(Baseline, Day 5)
- Change in ECG-QT Interval (Msec)(Baseline, Day 5)
- Change in ECG-QTc Interval (Msec)(Baseline, Day 5)
- Change in Aspartate Aminotransferase (AST) (U/L)(Baseline, Day 5)