FRDA Investigator Initiated Study (IIS) With Elamipretide (ELViS-FA)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Drug: Elamipretide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia - Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Genetically confirmed FRDA (point mutations allowed).
2. Age >16 years.
3. Disease onset before 18 years of age.
4. 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.
5. 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.
6. 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.

7. 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

8. 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:

1. Any unstable illness that in the investigator's opinion precludes participation in the study.
2. Use of any investigational product within 30 days prior to Screening.
3. A history of substance abuse.
4. Diagnosis of active HIV or Hepatitis B or C infection.
5. 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.
6. 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.
7. Any other active cause of optic neuropathy (Vitamin B12 deficiency, Vitamin E deficiency, etc.) or cardiac disease
8. EF less than 35% at last echocardiographic evaluation
9. Uncontrolled arrhythmia
10. Current use of any systemic chronic immunosuppressive drugs
11. Current use of Metformin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose (20-30mg); Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (20-30 mg) for 52 weeks	Drug: Elamipretide; 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.; Other Names: MTP-131; SS-31
Experimental: High Dose (40-60 mg); Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (40-60 mg) for 52 weeks	Drug: Elamipretide; 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.; Other Names: MTP-131; SS-31

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: Friedreich's Ataxia Research Alliance; Stealth BioTherapeutics Inc.
• Investigators: Principal Investigator: David Lynch, MD, PhD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 9, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 23, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Friedreich Ataxia
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia
• Other Study ID Numbers: 20-018049; SPIFA-101 (Other Identifier: Stealth Biotherapeutics, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No