FRDA Investigator Initiated Study (IIS) With Elamipretide

Phase 1

Completed

• Conditions: Friedreich Ataxia
• Interventions: Drug: Elamipretide

• Registration Number: NCT05168774
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

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

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 Timeline

• Study First Submitted: 2021-12-09
• Study First Submitted QC: 2021-12-09
• Study First Posted: 2021-12-23
• Study Start: 2022-03-03
• Primary Completion: 2024-06-25
• Study Completion: 2024-07-25
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-14
• Last Update Posted: 2024-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low Dose (20-30mg)	Elamipretide	Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (20-30 mg) for 52 weeks
High Dose (40-60 mg)	Elamipretide	Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (40-60 mg) for 52 weeks

Primary Outcome Measures

Name	Time	Method
Change in High Contrast Visual Acuity	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).

Secondary Outcome Measures

Name	Time	Method
Change in Low Contrast Visual Acuity	Baseline to 52 weeks	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).
Change in Low Luminescence Visual Activity	Baseline to 52 weeks	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).
Change in retinal nerve fiber layer by Optical Coherence Tomography (OCT)	Baseline to 52 weeks	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.
Change in visual quality of life by Visual Functioning Questionnaire (VFQ)	Baseline to 52 weeks	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).
Change in Cardiac Strain	Baseline to 36 weeks	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
Change in Cardiac Fibrosis	Baseline to 36 weeks	The change in cardiac fibrosis over time by T1 mapping using late gadolinium enhancement between groups (low dose and high dose).
Change Cardiac Stroke Volume	Baseline to 36 weeks	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).

Trial Locations

Locations (1)

Children's Hospital of Philadelphia - Neurology; 🇺🇸 Philadelphia, Pennsylvania, United States