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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Elamipretide to determine its effectiveness in treating vision loss caused by Friedreich Ataxia (FRDA), a rare disease affecting nerve and muscle function. Researchers aim to assess the medication's safety, tolerability, and efficacy at different doses. They seek participants with FRDA who experience vision issues, such as difficulty seeing clearly even with glasses, or have certain heart-related symptoms from this condition. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to early-stage treatment development.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Elamipretide has undergone safety testing in several clinical trials. In one study on mitochondrial diseases, most participants tolerated Elamipretide well, experiencing only mild side effects such as injection site reactions or mild headaches. The MMPOWER-3 study also found Elamipretide to be safe, with few reports of serious side effects.

The FDA has approved Elamipretide for treating Barth Syndrome, further supporting its safety. This approval indicates it is considered safe for humans, even though the condition in this trial differs.

Overall, past studies and FDA approval for other uses of Elamipretide suggest it is generally safe, though, like any medication, it may have some minor side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Friedreich Ataxia?

Researchers are excited about Elamipretide for Friedreich Ataxia vision loss because it offers a novel approach by targeting mitochondrial dysfunction, which is a core issue in this condition. Unlike current treatments that primarily focus on managing symptoms, Elamipretide works at the cellular level to potentially improve the health of the mitochondria, which could lead to better vision outcomes. Additionally, its delivery method via daily subcutaneous dosing provides a consistent and targeted approach, which may enhance its effectiveness over existing therapies.

What evidence suggests that Elamipretide might be an effective treatment for Friedreich Ataxia vision loss?

Research suggests that Elamipretide may help treat vision loss in people with Friedreich Ataxia (FRDA). Studies have shown that Elamipretide can improve mitochondrial function, which often declines in FRDA. Other research found that Elamipretide can increase levels of frataxin, a protein that might slow the disease's progression. Early results indicate that this treatment could help maintain or improve vision in FRDA patients. Although more research is needed, these initial findings offer promise for those affected by this condition. Participants in this trial will receive either a low dose (20-30 mg) or a high dose (40-60 mg) of Elamipretide daily for 52 weeks to further evaluate its effectiveness. ^{1 3 5 6 7}

Who Is on the Research Team?

David Lynch, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05168774

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

2. stealthbt.com stealthbt.com/programs-pipeline-copy/

Elamipretide Clinical Studies and Trials We are investigating elamipretide in late stage clinical studies in ophthalmic diseases entailing mitochondrial dysfunction, such as dry AMD, rare neuromuscular ...

3. curefa.org curefa.org/clinical-studies/a-pilot-investigator-initiated-study-to-evaluate-the-safety-tolerability-and-efficacy-of-elamipretide-in-the-treatment-of-advanced-symptoms-of-friedreich-ataxia-frda/

A Pilot Investigator Initiated Study to Evaluate the Safety ... Study Overview: To evaluate the safety, tolerability, and activity of Elamipretide in treating vision loss in Friedreich Ataxia (FRDA).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5575096/

Peptide SS-31 upregulates frataxin expression and ... Our results suggest that SS-31 might potentially be a new drug for the early treatment of Friedreich ataxia. Introduction. Friedreich ataxia ( ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10382259/

Efficacy and Safety of Elamipretide in Individuals With ... We present data from MMPOWER-3, a pivotal, phase-3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05168774

FRDA Investigator Initiated Study (IIS) With Elamipretide To evaluate the safety, tolerability, and activity of Elamipretide in treating vision loss in Friedreich Ataxia (FRDA). Detailed Description. To evaluate the ...

7. curefa.org curefa.org/drug-development/elamipretide/

Elamipretide (Brand Name FORZINITY™ for Barth ... The FDA has granted elamipretide Orphan Drug Designation for the treatment of patients with Friedreich's ataxia, and it has granted accelerated approval to ...