A Pilot Investigator Initiated Study to Evaluate the Safety, Tolerability and Efficacy of Elamipretide in the Treatment of Advanced Symptoms of Friedreich Ataxia (FRDA)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in High Contrast Visual Acuity
研究概览
简要总结
To evaluate the safety, tolerability, and activity of Elamipretide in treating vision loss in Friedreich Ataxia (FRDA).
详细描述
To evaluate the effect of high dose (40-60mg) versus low dose (20-30mg) Elamipretide on high contrast visual acuity in FRDA compared to baseline at 52 weeks with the option to extend for an additional 52 weeks if there are objective signs of clinical improvement on primary or secondary endpoints. The interim analysis will be based on data from a 36-week visit. For subjects worse than 20/800 at study start, they will be followed using low vision alternatives only.
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
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically confirmed FRDA (point mutations allowed).
- •Age >16 years.
- •Disease onset before 18 years of age.
- •If female, the subject is not pregnant or lactating or intending to become pregnant before, during, or within 30 days after the last dose of study drug. Female subjects of child-bearing potential must have a negative serum pregnancy test result at Screening, a negative urine pregnancy test result at Baseline.
- •All subjects must agree to use a reliable method of contraception throughout the study and for 30 days after the last dose of study drug. Male subjects should not father a baby during the study or for at least 30 days after the last dose of study drug.
- •All concomitant medications (including over-the-counter medications), vitamins, and supplements must be at stable doses for 30 days prior to study entry and kept stable throughout the study to the best of their ability.
- •Visual acuity (VA) worse than 20/40 (binocular) on the basis of FRDA. Must not be correctable by refraction, or subjects must have sufficient physical exam findings of optic neuropathy (funduscopic, visual fields, or retinal ganglion cell loss) to justify the primary diagnosis of FRDA related optic neuropathy
- •Ejection Fraction (EF) less than 50% at last evaluation (within 1 year before screening), with a history consistent with cardiomyopathy from FRDA, and VA 20/25- 20/40.
排除标准
- •Any unstable illness that in the investigator's opinion precludes participation in the study.
- •Use of any investigational product within 30 days prior to Screening.
- •A history of substance abuse.
- •Diagnosis of active HIV or Hepatitis B or C infection.
- •Presence of severe renal disease (eGFR <30 mL/min) or hepatic disease [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x the upper limit of normal] as evidenced by laboratory results at Screening.
- •Clinically significant abnormal white blood cell count (ANC <1500), hemoglobin (< 9.0 gm/dL), or platelet count (100 K or >500 K) as evidenced by laboratory test results at Screening.
- •Any other active cause of optic neuropathy (Vitamin B12 deficiency, Vitamin E deficiency, etc.) or cardiac disease
- •EF less than 35% at last echocardiographic evaluation
- •Uncontrolled arrhythmia
- •Current use of any systemic chronic immunosuppressive drugs
- •Current use of Metformin
研究组 & 干预措施
Low Dose (20-30mg)
Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (20-30 mg) for 52 weeks
干预措施: Elamipretide (Drug)
High Dose (40-60 mg)
Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (40-60 mg) for 52 weeks
干预措施: Elamipretide (Drug)
结局指标
主要结局
Change in High Contrast Visual Acuity
时间窗: Baseline to 52 weeks
Change in High Contrast Visual Acuity will be measured by assessing the differences in the number of letters read (binocular) on the ETDRS High Contrast Visual Acuity Chart between groups (low dose and high dose).
次要结局
- Change in Cardiac Strain(Baseline to 36 weeks)
- Change in Cardiac Fibrosis(Baseline to 36 weeks)
- Change Cardiac Stroke Volume(Baseline to 36 weeks)
- Change in Low Contrast Visual Acuity(Baseline to 52 weeks)
- Change in Low Luminescence Visual Activity(Baseline to 52 weeks)
- Change in Retinal Nerve Fiber Layer by Optical Coherence Tomography (OCT)(Baseline to 52 weeks)
- Change in Visual Quality of Life by Visual Functioning Questionnaire (VFQ)(Baseline to 52 weeks)
研究者
David Lynch
Professor of Neurology in Pediatrics at the Children's Hospital of Philadelphia
Children's Hospital of Philadelphia