Clinical trial NCT06373731: ReNEW:Phase 3 Study of Efficacy, Safety & Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration (Dry AMD)
Official title: ReNEW: A Phase 3, Double-Masked, Placebo-Controlled Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects Who Have Dry Age-Related Macular Degeneration (Dry AMD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Age Related Macular Degeneration (ARMD)
Keywords: dAMD, Dry AMD, dryAMD
Macular degeneration
non-central geographic atrophy, GA
MTP-131
elamipretide
Non- Intravitreal, Non- gene therapy
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2024-04-18
Enrollment: 360
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized (2:1) to once daily 40 mg SC of elamipretide or placebo for 96 weeks of treatment by a central randomization
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The ReNEW (SPIAM-301) trial is a phase 3, randomized, double-masked, parallel-group, placebo-controlled clinical trial to evaluate the efficacy, safety, and pharmacokinetics of a once daily subcutaneous (SC) injection of elamipretide in subjects who have dry AMD. Subjects will be randomized (2:1) to once daily SC doses of 40 mg elamipretide, or placebo for 96 weeks of treatment by a central randomization and stratified by SD-OCT device type (Heidelberg SPECTRALIS®, ZEISS CIRRUS®) and baseline macular area of photoreceptor loss, defined as an ellipsoid zone-retinal pigment epithelium (EZ-RPE) thickness of 0μm assessed by SD-OCT and ellipsoid zone (EZ) mapping (High Strata ≥ 5.1mm2, Low Strata \<5.1mm2).

Primary Objective

* Evaluate the efficacy of once daily subcutaneous (SC) injections of elamipretide in subjects who have dry age-related macular degeneration (AMD) Secondary Objectives
* Evaluate the safety and tolerability of once daily SC injections of elamipretide
* Evaluate the Pharmacokinetic (PK) profile of elamipretide and its metabolites

Eligibility criteria: Inclusion Criteria:

A subject must meet all the inclusion criteria at the Screening and Baseline Visit (unless otherwise specified) to be eligible for inclusion in the trial.

1. Adults ≥ 55 years of age with at least 1 eye with dry AMD with photoreceptor loss, as determined at the Screening Visit by the presence of extrafoveal geographic atrophy (GA), as determined by the Reading Center primarily by fundus autofluorescence (FAF). For this trial, extrafoveal GA is defined as:

   1. well-demarcated area(s) of GA
   2. All GA lesions must be at least 150 μm from foveal center Note: The fellow eye may have any of the following: no AMD, AMD without GA, AMD with GA, CNV AMD, or foveal GA (ongoing treatment with anti-angiogenic therapies and/or complement inhibitor therapies in the fellow eye is allowable)

   Ocular conditions - Study Eye:
2. GA in the study eye at the Screening Visit may be multi-focal, but the cumulative GA lesion and size (by FAF, as determined by the Reading Center) must:

   1. be ≥ 0.50 mm2 and ≤ 10.16 mm2 AND
   2. reside completely within the FAF 30- or 35-degree image
3. BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) score of ≥ 55 letters in the study eye
4. LL BCVA by ETDRS score of ≥ 10 letters in the study eye
5. LLD (defined as the difference between BCVA and LL BCVA) of \> 5 letters in the study eye
6. Sufficiently clear ocular media, adequate pupillary dilation, fixation to permit quality fundus imaging, and ability to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment in the study eye

   Systemic and General Criteria:
7. Able to administer IMP or have an appropriate designee who can administer the IMP (i.e., a capable family member or a caregiver)
8. Able to provide informed consent and willing to comply with all site visits, examinations, daily IMP administrations and dosing diary entries, and other conditions of the trial protocol
9. Women of childbearing potential must agree to use 1 of the following methods of contraception from the date they sign the ICF until 28 days after the last dose of IMP:

   1. Abstinence, when it is in line with the preferred and usual lifestyle of the subject; Subject agrees to use a highly effective method of contraception should they become sexually active
   2. Relationships with male partners who have been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit)
   3. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine device or system Note: Non-childbearing potential is defined as surgical sterilization (e.g., bilateral oophorectomy, hysterectomy, or tubal ligation) or postmenopausal (defined as permanent cessation of menstruation for at least 12 consecutive months prior to the Screening Visit).
10. Male subjects with female partners of childbearing potential must be willing to use a highly effective method of contraception (e.g., abstinence, dual method of contraception) from the date they sign the ICF until 28 days after the last dose of IMP

Exclusion Criteria:

Subjects who meet any of the following criteria at the Screening and Baseline Visit (unless otherwise specified) will be excluded from the trial:

Ocular Conditions - Study Eye:

1. The absence of observable hyper-FAF at the margins of the GA in the study eye at the Screening Visit by the Reading Center
2. Atrophic retinal disease of causality other than AMD including myopia-related maculopathy and monogenetic macular dystrophies including pattern dystrophy and adult-onset Stargardt disease in the study eye
3. Evidence of exudative AMD or CNV in the study eye by history or FA , as determined by the Reading Center
4. Presence of retinal vein occlusion in the study eye
5. Presence of vitreous hemorrhage in the study eye
6. History of retinal detachment in the study eye
7. History of macular hole (stages 2 to 4) in the study eye
8. Presence of an epiretinal membrane and/or vitreomacular traction in the study eye that causes distortion of the retinal contour
9. Presence of any retinal pathology in the study eye that prohibits outer retinal quantification and EZ mapping, as determined at the Screening Visit by the Reading Center
10. At the Screening Visit, advanced glaucoma resulting in a cup to disc ratio of \> 0.8 in the study eye
11. History of glaucoma filtration surgery or uncontrolled glaucoma at Baseline Visit in the opinion of the Investigator OR currently using ≥ 3 medications (Minimally invasive glaucoma surgeries (e.g., MIGS) are allowable) Note: Combination medications count as 2 medications.
12. Presence of visually significant cataract OR presence of significant posterior capsular opacity in the setting of pseudophakia Note: Significant cataract is defined as ≥ +3 nuclear sclerosis based upon the scale below or any Posterior Subcapsular Cataract in the study eye. The Sponsor, or its designee, will supply the clinical trial sites with a copy of the standard photographs. Grade Description

    * 1 Opacity is absent
    * 2 Opacity is present, but less than Nuclear Standard Photograph #2
    * 3 Opacity is present, and as severe as or worse than Nuclear Standard Photograph #2 Source: (Chew 2010)
13. Presence of significant keratopathy or any other media or corneal opacity that would cause scattering of light or alter visual function, especially in LL conditions in the study eye
14. Ocular incisional or laser surgery (including cataract surgery) in the study eye within 90 days before the Baseline Visit
15. YAG laser capsulotomy in the study eye within 30 days before the Baseline Visit
16. Aphakia in the study eye
17. History of vitrectomy surgery, submacular surgery, or any vitreoretinal surgery in the study eye
18. Prior treatment with Visudyne® (verteporfin) ocular photodynamic therapy, external-beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy in the study eye
19. History of subthreshold laser treatment or other forms of photobiomodulation for AMD in the study eye
20. Intravitreal drug delivery in the past 60 days or 5-half-lives from the Baseline Visit of the injected drug whichever is longer (e.g., intravitreal corticosteroid injection, anti-angiogenic drugs, or device implantation) in the study eye
21. Intravitreal drug delivery of a complement inhibitor in the past 6 months from the Baseline Visit in the study eye
22. Concurrent disease in the study eye that could require medical or surgical intervention during the trial

    Ocular conditions - Either Eye:
23. Presence or a history of diabetic retinopathy in either eye (a history of diabetes mellitus without retinopathy is not a criterion for exclusion)
24. History of herpetic infection in either eye
25. Active uveitis and/or vitritis (grade trace or above) in either eye
26. History of idiopathic or autoimmune-associated uveitis in either eye
27. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye

    Systemic Conditions:
28. Has a history of a systemic eosinophilic illness and/or an eosinophil count \>1,000 cells x106/L (equivalent to \>1 cell x 103/μL) at the Screening Visit
29. History of solid organ transplant
30. Any disease or medical condition that in the opinion of the Investigator would prevent the subject from successfully participating in the trial or might confound trial results
31. Current use of medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine \[Plaquenil®\], tamoxifen, phenothiazines, ethambutol, digoxin, and aminoglycosides)
32. eGFR of \< 30 mL/min at the Screening Visit (using the CKD-EPI 2021 formula)

    General Conditions:
33. Participation in other investigational drug or device clinical trials within 30 days or 5 half-lives (whichever is longer) of Screening; or is currently enrolled in a non-interventional clinical trial that, in the opinion of the Investigator, may be potentially confounding to the results of the current trial
34. Women who are pregnant, planning to become pregnant, or breastfeeding/lactating
35. History of allergy to fluorescein that is not amenable to treatment
36. Inability to comply with trial or follow-up procedures
37. Inability to obtain CFP, FAF, and FA of sufficient quality to be analyzed and interpreted
38. Active malignancy or any other cancer from which the subject has been cancer-free for \< 2 years. Localized squamous or non-invasive basal cell skin carcinomas are allowed, if appropriately treated prior to screening
39. History of allergic reaction to the investigational drug or any of its components
40. Prior participation in any elamipretide trial

Primary outcomes:
measure: Week 48 Rate of change in the macular area of photoreceptor loss
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Week 72 Rate of change in the Macular area of photoreceptor loss
timeFrame: Baseline, Week 72
measure: Week 96 Rate of change in the Macular area of photoreceptor loss
timeFrame: Baseline, Week 96
measure: Proportion of subjects gaining ≥ 10 letters (2 lines) in Low Luminance Best-Corrected Visual Acuity (LL BCVA)
timeFrame: Baseline, Week 48
measure: Proportion of subjects gaining ≥ 15 letters in Low Luminance Best-Corrected Visual Acuity (LL BCVA)
timeFrame: Baseline, Week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Sun City
country: United States
facility: Barnet Dulaney Perkins Eye Center
state: Arizona
city: Huntington Beach
country: United States
facility: Retina Associates of Southern California
state: California
city: Poway
country: United States
facility: Retina Consultants of San Diego
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group
state: California
city: Santa Ana
country: United States
facility: Orange County Retinal Medical Group
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Colorado Springs
country: United States
facility: Retina Consultants of Southern Colorado
state: Colorado
city: Danbury
country: United States
facility: Connecticut Eye Consultants, P.C.
state: Connecticut
city: Clearwater
country: United States
facility: Blue Ocean Clinical Research Center
state: Florida
city: Gainesville
country: United States
facility: Vitreo Retinal Associates
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Oak Forest
country: United States
facility: University Retina and Macula Associates
state: Illinois
city: Carmel
country: United States
facility: Associated Vitreoretinal and Uveitis Consultants
state: Indiana
city: Hagerstown
country: United States
facility: Mid Atlantic Retina Specialist
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center
state: Michigan
city: Minneapolis
country: United States
facility: Retina Consultants of Minnesota
state: Minnesota
city: Cherry Hill
country: United States
facility: Mid Atlantic Retina
state: New Jersey
city: Teaneck
country: United States
facility: NJ Retina
state: New Jersey
city: Cincinnati
country: United States
facility: MidWest Eye Center
state: Ohio
city: Edmond
country: United States
facility: Retina Vitreous Center
state: Oklahoma
city: Portland
country: United States
facility: Retina Northwest, PC
state: Oregon
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Clinical Research, LLC
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
city: Plano
country: United States
facility: Texas Retina Associates of Plano
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Texas
state: Texas
city: Falls Church
country: United States
facility: Emerson Clinical Research Institute
state: Virginia
city: Norfolk
country: United States
facility: Wagner Kapoor Research Institute
state: Virginia
city: Silverdale
country: United States
facility: Pacific Northwest Retina, PLLC
state: Washington
city: Pardubice
country: Czechia
facility: Oftex Eye Clinic
city: Praha
country: Czechia
facility: Axon Clinical, s.r.o.
city: Praha
country: Czechia
facility: Ocni klinika
city: Bonn
country: Germany
facility: Universitäts-Augenklinik
city: Kiel
country: Germany
facility: Klinik für Ophthalmologie, UKSH Kiel
city: Münster
country: Germany
facility: Augenzentrum am St. Franziskus-Hospital
city: Regensburg
country: Germany
facility: Klinik und Poliklinik für Augenheilkunde- Universitätsklinik Regensburg
city: Tübingen
country: Germany
facility: Department für Augenheilkunde
city: Debrecen
country: Hungary
facility: University Of Debrecen Eye Center
city: Pécs
country: Hungary
facility: Ganglion Medical Center
city: Szeged
country: Hungary
facility: University of Szeged, Department of Ophthalmology
city: Milano
country: Italy
facility: Hospital Luigi Sacco Ophthalmology Dept
city: Milano
country: Italy
facility: IRRCS Ospendale San Raffaele
city: Milano
country: Italy
facility: Policlinico Milano
city: Roma
country: Italy
facility: Fondazione Policlinico Gemelli
city: Udine
country: Italy
facility: Department of Ophthalmology, Azienda SanitariaUniversitaria Friuli Centrale
city: Christchurch
country: New Zealand
facility: Southern Eye Specialists
city: Wellington
country: New Zealand
facility: Capital Eye Specialists
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Barcelona
country: Spain
facility: OMIQ Research
city: Valencia
country: Spain
facility: Fundacion Aiken de la Comunitat Valenciana
city: Valencia
country: Spain
facility: Oftalvist
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust - Bristol Eye Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester, Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Macular Services, Central Middlesex Hospital, NHS Foundation Trust
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
city: Salisbury
country: United Kingdom
facility: Salisbury NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Sunderland
country: United Kingdom
facility: South Tyneside and Sunderland NHS Foundation Trust - Sunderland Eye Infirmary
Study officials:
affiliation: Stealth BioTherapeutics
name: Rekha Sathyanarayana
role: STUDY_DIRECTOR
References: