Elamipretide for Age-Related Macular Degeneration

(ReNEW Trial)

Not currently recruiting at 65 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, elamipretide, for individuals with dry age-related macular degeneration (AMD), a condition that affects the eyes and can lead to vision loss. Researchers aim to determine if elamipretide can slow vision deterioration and assess its safety compared to a placebo (a substance with no active drug). Participants will receive daily injections and will be compared to those receiving the placebo. Suitable candidates for this trial are adults over 55 with dry AMD and vision loss that does not affect the center of the eye. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for AMD.

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.

Is there any evidence suggesting that elamipretide is likely to be safe for humans?

Research has shown that elamipretide is generally safe for people. In an earlier study on dry age-related macular degeneration (AMD), most participants did not experience serious side effects. Some had mild reactions, such as redness or discomfort at the injection site. Another study supported these results, confirming that elamipretide is safe for people with dry AMD. Currently, this treatment is being tested in a late-stage trial, indicating that earlier trials found it safe enough for further study. ^{1 2 3 4 5}

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

Unlike the standard treatments for age-related macular degeneration (AMD), which often include anti-VEGF injections targeting abnormal blood vessel growth, Elamipretide offers a novel approach. Elamipretide works by targeting the mitochondria within retinal cells, potentially improving cellular energy production and function. This new mechanism of action could protect against cellular damage and slow the progression of AMD. Researchers are excited because this mitochondria-targeting strategy may offer benefits beyond current therapies, potentially improving vision preservation and overall eye health.

What evidence suggests that elamipretide might be an effective treatment for age-related macular degeneration?

Research has shown that elamipretide, which participants in this trial may receive, may help treat dry age-related macular degeneration (AMD). In earlier studies, patients with noncentral geographic atrophy, a type of vision loss linked to AMD, experienced positive results after receiving elamipretide. This treatment improves the function of mitochondria, the energy centers in cells, which is believed to help protect eye cells from further damage. Although more research is needed, early results suggest that elamipretide could slow vision loss in AMD. ^{1 2 3 4 6}

Who Is on the Research Team?

Rekha Sathyanarayana

Principal Investigator

Stealth BioTherapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11599447/

ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating ... This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA).

2. ophthalmologyscience.org ophthalmologyscience.org/article/S2666-9145(21)00088-9/fulltext

Phase 1 Clinical Trial of Elamipretide in Dry Age-Related ... Assess the safety, tolerability, and feasibility of subcutaneous administration of the mitochondrial-targeted drug elamipretide in patients with dry age- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06373731

NCT06373731 | ReNEW:Phase 3 Study of Efficacy, Safety ... The goal of this clinical trial is to evaluate the efficacy, safety and pharmacokinetics of elamipretide in subjects with dry age-related macular degeneration ...

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

Elamipretide Clinical Studies and Trials ReNEW is a Phase 3 global clinical trial evaluating the efficacy and safety of once-daily subcutaneous injections of elamipretide in participants with dry AMD.

5. isrctn.com isrctn.com/ISRCTN59733193

ReNEW: a clinical trial investigating the efficacy and safety ... The main objective of the trial is to evaluate the efficacy of daily injections of elamipretide in subjects who have dry age-related macular degeneration (AMD).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02848313

NCT02848313 | An Open-Label, Phase 1 Clinical Study to ... An Open-Label, Phase 1 Clinical Study to Evaluate the Safety and Tolerability of Subcutaneous Elamipretide in Subjects With Intermediate Age-Related Macular ...