FRDA Investigator Initiated Study (IIS) With Elamipretide

Study Overview
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Brief Summary
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To evaluate the safety, tolerability, and activity of Elamipretide in treating vision loss in Friedreich Ataxia (FRDA).

Detailed Description
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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.

Official Title
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A Pilot Investigator Initiated Study to Evaluate the Safety, Tolerability and Efficacy of Elamipretide in the Treatment of Advanced Symptoms of Friedreich Ataxia (FRDA)

Conditions
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Friedreich Ataxia

Intervention / Treatment
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* Drug: Elamipretide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Or 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose (20-30mg)<br>Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (20-30 mg) for 52 weeks | Drug: Elamipretide<br>* Elamipretide is a tetra peptide with limited blood brain barrier penetration being developed for use in a variety of mitochondrial disorders, including FRDA, mitochondrial myopathy and Barth Syndrome.<br>* Other names: SS-31;|
| Experimental: High Dose (40-60 mg)<br>Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (40-60 mg) for 52 weeks | Drug: Elamipretide<br>* Elamipretide is a tetra peptide with limited blood brain barrier penetration being developed for use in a variety of mitochondrial disorders, including FRDA, mitochondrial myopathy and Barth Syndrome.<br>* Other names: SS-31;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in High Contrast Visual Acuity | 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). | Baseline to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Low Contrast Visual Acuity | Change in Low Contrast Visual Acuity will be measured by assessing the differences in the number of letters read (binocular) on the ETDRS Low Contrast Visual Acuity Chart between groups (low dose and high dose). | Baseline to 52 weeks | 
| Change in Low Luminescence Visual Activity | Change in Low Luminescence Visual Acuity will be measured by assessing the difference in the number of letters read (binocular) on the ETDRS High Contrast Visual Acuity Chart with Low Luminescence Filter between groups (low dose and high dose). | Baseline to 52 weeks | 
| Change in retinal nerve fiber layer by Optical Coherence Tomography (OCT) | The change in thickness of the retinal nerve fiber layer between groups (low dose and high dose) will be measured using the OCT, a non-invasive imaging test that uses light waves to take cross-section pictures of the retina. | Baseline to 52 weeks | 
| Change in visual quality of life by Visual Functioning Questionnaire (VFQ) | The VFQ is a 25 item patient reported outcome on visual symptomology to assess change in patient self-report of visual ability over time compared to baseline between groups (low dose and high dose). | Baseline to 52 weeks | 
| Change in Cardiac Strain | The change in cardiac strain (dL/L) in each dimension per cardiac cycle between groups (low dose and high dose) is measured by speckle tracking on imaging | Baseline to 36 weeks | 
| Change in Cardiac Fibrosis | The change in cardiac fibrosis over time by T1 mapping using late gadolinium enhancement between groups (low dose and high dose). | Baseline to 36 weeks | 
| Change Cardiac Stroke Volume | The change in stroke volume will be calculated by Ejection Fraction x Ventricular Volume x Pulse Rate, over time between groups (low dose and high dose). | Baseline to 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Friedreich Ataxia