Elamipretide for Age-Related Macular Degeneration

(ReNEW Trial)

Recruiting at 62 trial locations

Overseen By Rekha Sathyanarayana

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Stealth BioTherapeutics Inc.

Must not be taking: Plaquenil, Tamoxifen, Digoxin, others

Disqualifiers: Diabetic retinopathy, Organ transplant, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

360 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate the efficacy, safety and pharmacokinetics of elamipretide in subjects with dry age-related macular degeneration (AMD). The main questions it aims to answer are: what is the rate of change in the macular area of photoreceptor loss in subjects who receive a daily dose of elamipretide compared with those who receive a look-alike substance that contains no active drug, and what is the safety and tolerability of elamipretide daily subcutaneous injections. Participants will receive either once daily subcutaneous doses of 40mg elamipretide or placebo and the two treatment groups will be compared.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are using medications known to be toxic to the eye, like chloroquine or tamoxifen.

What data supports the effectiveness of the drug Elamipretide for age-related macular degeneration?

The Phase 1 Clinical Trial of Elamipretide in Dry Age-Related Macular Degeneration and Noncentral Geographic Atrophy (ReCLAIM NCGA Study) assessed the safety and feasibility of Elamipretide, with exploratory analyses on changes in visual function, suggesting potential benefits in visual improvement. ^{1 2 3 4 5}

How is the drug Elamipretide unique for treating age-related macular degeneration?

Elamipretide is unique because it targets mitochondria (the energy-producing parts of cells) to improve their function, which may help slow or reverse visual decline in age-related macular degeneration. Unlike other treatments that focus on reducing inflammation or preventing blood vessel growth, Elamipretide specifically enhances mitochondrial efficiency, potentially offering a novel approach to managing this condition. ^{2 6 7 8 9}

Research Team

Rekha Sathyanarayana

Principal Investigator

Stealth BioTherapeutics

Eligibility Criteria

This trial is for people with dry age-related macular degeneration (AMD). Participants should have a specific level of vision loss and clear enough eyes for imaging. They must be able to take daily injections or have someone who can administer them. Those with certain other eye conditions or treatments are excluded.

Inclusion Criteria

Able to provide informed consent and willing to comply with all trial conditions

I can take the study medication myself or have someone who can do it for me.

I agree to use birth control if I can have children.

Exclusion Criteria

Absence of observable hyper-FAF at the margins of the GA in the study eye

My vision loss is not due to AMD.

My kidney function is severely reduced.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once daily subcutaneous doses of 40mg elamipretide or placebo for 96 weeks

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Elamipretide

Trial Overview The study tests the effectiveness and safety of elamipretide, administered through daily shots, against a placebo in slowing down photoreceptor loss in the retina due to dry AMD. The comparison will help determine if elamipretide can benefit patients with this condition.

Participant Groups

Group I: Elamipretide Experimental Treatment 1 Intervention

Subjects will receive once daily subcutaneous doses of 40mg elamipretide for 96 weeks

Group II: Placebo Placebo Group 1 Intervention

Subjects will receive once daily subcutaneous doses of placebo for 96 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?

Stealth BioTherapeutics Inc.

Lead Sponsor

Trials

29

Recruited

2,300+

Findings from Research

In a Phase 2 clinical trial with 123 patients suffering from neovascular age-related macular degeneration, the modified manufacturing process of abicipar resulted in a lower incidence of intraocular inflammation (IOI), with only 8.9% of patients experiencing this side effect, and most cases were mild and resolved with treatment.

The treatment was effective, with over 95.9% of patients maintaining stable vision throughout the study, and treatment-naïve patients showed greater improvements in visual acuity and retinal thickness compared to those previously treated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Modifying Abicipar Manufacturing Process in Patients with Neovascular Age-Related Macular Degeneration: MAPLE Study Results. Callanan, D., Khurana, RN., Maturi, RK., et al.[2023]

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]

Abicipar pegol showed comparable efficacy in improving visual acuity and reducing retinal thickness in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) in both Japan and the United States, with mean visual acuity changes of +7.8 to +8.9 letters in Japan and +4.4 to +10.1 letters in the U.S. after 16 weeks.

The treatment was generally safe, with only three cases of uveitis or vitritis reported among abicipar-treated patients, indicating a favorable safety profile for this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Patients With Neovascular Age-Related Macular Degeneration: Studies in Japan and the United States. Kunimoto, D., Ohji, M., Maturi, RK., et al.[2019]

In a study of 28 patients with refractory wet age-related macular degeneration, switching to high-dose aflibercept (4 mg every 4 weeks) led to a dry retina in an average of 3.8 months, demonstrating its efficacy in treating resistant cases.

The treatment resulted in significant reductions in retinal fluid and thickness, with 45% of patients experiencing improved vision, and importantly, no serious adverse events were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIGH-DOSE HIGH-FREQUENCY AFLIBERCEPT FOR RECALCITRANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. You, QS., Gaber, R., Meshi, A., et al.[2019]

In a 3-year follow-up study of 19 patients with neovascular age-related macular degeneration (AMD), maintenance therapy with intravitreal pegaptanib sodium effectively stabilized vision, with significant improvement in best-corrected visual acuity (BCVA) maintained over time.

The treatment also resulted in a significant reduction in central foveal thickness (CFT), indicating anatomical improvement, and no severe side effects were reported, highlighting the safety of pegaptanib as a long-term therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of intravitreal pegaptanib sodium as maintenance therapy in Japanese patients with neovascular age-related macular degeneration. Inoue, M., Kadonosono, K., Arakawa, A., et al.[2022]

There is a significant need for new treatments for dry age-related macular degeneration (AMD), and repurposing existing FDA-approved drugs presents a promising strategy.

Several classes of drugs, including GPR-143 agonists, anti-diabetic medications, mitochondrial activators, and serotonin pathway drugs, are being explored for their potential to reduce AMD diagnosis, highlighting the innovative approach of using existing medications for new therapeutic purposes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing Drugs for Treatment of Age-Related Macular Degeneration. Francisco, SG., Rowan, S.[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]

In the VISION-1 trial involving 1186 patients, pegaptanib, a VEGF inhibitor, significantly helped maintain visual acuity in patients with neovascular age-related macular degeneration, with 70% of those receiving the 0.3 mg dose losing fewer than 15 letters of visual acuity compared to 55% in the sham group.

While pegaptanib showed no serious systemic side effects, it did lead to more ocular adverse effects, such as vitreous floaters and inflammation, indicating a need for ongoing improvements in treatment options for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegaptanib: the first antiangiogenic agent approved for neovascular macular degeneration. Doggrell, SA.[2019]

Emerging treatments for dry age-related macular degeneration (AMD) focus on two main strategies: preventing cell loss through neuroprotection and oxidative damage prevention, and suppressing inflammation.

Current and potential therapies include neuroprotective drugs, micronutrient supplementation, visual cycle modulators, and anti-inflammatory agents, suggesting a combination approach may be most effective in managing AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New approaches and potential treatments for dry age-related macular degeneration. Damico, FM., Gasparin, F., Scolari, MR., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Impact of Modifying Abicipar Manufacturing Process in Patients with Neovascular Age-Related Macular Degeneration: MAPLE Study Results. [2023]

2. 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]

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

Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Patients With Neovascular Age-Related Macular Degeneration: Studies in Japan and the United States. [2019]

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

HIGH-DOSE HIGH-FREQUENCY AFLIBERCEPT FOR RECALCITRANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

Long-term outcome of intravitreal pegaptanib sodium as maintenance therapy in Japanese patients with neovascular age-related macular degeneration. [2022]

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

Repurposing Drugs for Treatment of Age-Related Macular Degeneration. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Pegaptanib: the first antiangiogenic agent approved for neovascular macular degeneration. [2019]

9. Brazil pubmed.ncbi.nlm.nih.gov

New approaches and potential treatments for dry age-related macular degeneration. [2022]