Elamipretide for Friedreich Ataxia Vision Loss

(ELViS-FA Trial)

Overseen By McKenzie Wells

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital of Philadelphia

Must not be taking: Immunosuppressants, Metformin

Disqualifiers: Substance abuse, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Elamipretide, a drug that may help improve vision in patients with Friedreich Ataxia (FRDA). Elamipretide has been studied for its protective effects on eye cells. The study will compare high and low doses of the drug to see if it improves vision.

Do I need to stop my current medications for the trial?

You need to keep all your current medications, vitamins, and supplements at stable doses for 30 days before joining the study and throughout the study. However, you cannot participate if you are currently using Metformin or any systemic chronic immunosuppressive drugs.

Is Elamipretide safe for humans?

Elamipretide has been tested in humans for various conditions, including age-related macular degeneration and mitochondrial myopathy, and these studies generally focus on assessing its safety and tolerability. While specific safety outcomes are not detailed here, the fact that multiple studies have been conducted suggests that it has been considered safe enough to test in humans. ^{1 2 3 4 5}

How is the drug Elamipretide unique for treating Friedreich Ataxia vision loss?

Elamipretide is unique because it targets mitochondrial dysfunction, which is a key issue in Friedreich Ataxia, by helping to improve the function of mitochondria (the energy-producing parts of cells). This approach is different from other treatments that may not specifically address mitochondrial health. ^{6 7 8 9 10}

Research Team

David Lynch, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for individuals over 16 with Friedreich Ataxia (FRDA) causing vision loss and/or cardiomyopathy. Participants must have stable medication use for 30 days prior, visual acuity worse than 20/40 not correctable by glasses, and an ejection fraction less than 50%. They should agree to contraception use and not be pregnant or planning pregnancy. Genetic confirmation of FRDA is required.

Inclusion Criteria

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

My medications and supplements have been the same for the last 30 days.

My vision is worse than 20/40 due to FRDA and cannot be corrected.

Exclusion Criteria

You have very low white blood cell count, low hemoglobin, or very high or very low platelet count based on a blood test.

Use of any investigational product within 30 days prior to Screening

I am currently taking Metformin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily subcutaneous dosing of Elamipretide (20-60 mg) for 52 weeks

52 weeks

Interim Analysis

Interim analysis based on data from a 36-week visit

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Option to extend treatment for an additional 52 weeks if there are objective signs of clinical improvement

52 weeks

Treatment Details

Interventions

• Elamipretide

Trial Overview The study tests Elamipretide's safety and effectiveness in treating vision loss associated with FRDA. It aims to understand how well the drug can be tolerated by patients and its impact on their condition.

Participant Groups

Group I: Low Dose (20-30mg) Experimental Treatment 1 Intervention

Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (20-30 mg) for 52 weeks

Group II: High Dose (40-60 mg) Experimental Treatment 1 Intervention

Subjects will receive daily subcutaneous (SC) dosing of Elamipretide (40-60 mg) for 52 weeks

Elamipretide is already approved in United States for the following indications:

Approved in United States as Elamipretide for:

• Pending FDA approval for Barth syndrome and primary mitochondrial myopathy

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Stealth BioTherapeutics Inc.

Industry Sponsor

Trials

29

Recruited

2,300+

Friedreich's Ataxia Research Alliance

Collaborator

Trials

20

Recruited

6,400+

Findings from Research

In a Phase 1 clinical trial involving 19 participants with dry age-related macular degeneration (AMD), subcutaneous elamipretide was found to be well tolerated, with all adverse events being mild to moderate and no serious adverse events reported.

Exploratory analyses indicated that elamipretide may improve visual function, particularly in low-light conditions, with significant increases in best-corrected visual acuity (BCVA) and low-luminance BCVA (LLBCVA) observed after 24 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Clinical Trial of Elamipretide in Dry Age-Related Macular Degeneration and Noncentral Geographic Atrophy: ReCLAIM NCGA Study. Mettu, PS., Allingham, MJ., Cousins, SW.[2023]

In aged mice, visual function declined significantly with age, showing a 40% reduction in photopic acuity by 34 months, highlighting the impact of age-related neural dysfunction on vision.

Treatment with the mitochondrion-penetrating peptide elamipretide improved visual function when administered daily, reversing visual decline and normalizing function within 2 months, suggesting potential for treating age-related visual impairments in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of age-related visual impairment with a peptide acting on mitochondria. Alam, NM., Douglas, RM., Prusky, GT.[2022]

Lenadogene nolparvovec (Lumevoq) demonstrated a good safety profile in a pooled analysis of 189 patients with Leber hereditary optic neuropathy, with most adverse events being mild and manageable, particularly intraocular inflammation which was resolved with topical corticosteroids.

The treatment showed excellent systemic tolerability and limited bio-dissemination, indicating that it is well tolerated overall, with no serious treatment-related adverse events leading to study discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy. Vignal-Clermont, C., Yu-Wai-Man, P., Newman, NJ., et al.[2023]

Anecortave acetate is a novel angiostatic cortisene being investigated for treating age-related macular degeneration, with a focus on its pharmacological properties and clinical trial results.

The manuscript summarizes findings from multi-centre, randomized controlled trials targeting subfoveal choroidal neovascularization, indicating its potential effectiveness in managing both dry and wet forms of age-related macular degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anecortave acetate. Bakri, SJ., Kaiser, PK.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Phase 1 Clinical Trial of Elamipretide in Dry Age-Related Macular Degeneration and Noncentral Geographic Atrophy: ReCLAIM NCGA Study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of age-related visual impairment with a peptide acting on mitochondria. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects With Leber's Hereditary Optic Neuropathy: A Randomized Trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Safety of Lenadogene Nolparvovec Gene Therapy Over 5 Years in 189 Patients With Leber Hereditary Optic Neuropathy. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Anecortave acetate for the treatment of idiopathic perifoveal telangiectasia: a pilot study. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Posterior juxtascleral depot administration of anecortave acetate. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Anecortave acetate. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Anecortave acetate for the treatment of exudative age-related macular degeneration--a review of clinical outcomes. [2013]

10. Germany pubmed.ncbi.nlm.nih.gov

Antifibrotic effects of pirfenidone on Tenon's fibroblasts in glaucomatous eyes: comparison with mitomycin C and 5-fluorouracil. [2022]