Clinical trial NCT03891875: ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GA
Official title: A Phase 2 Randomized, Double-Masked, Placebo-Controlled Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Elamipretide in Subjects With Age-Related Macular Degeneration With Non-central Geographic Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Age-related Macular Degeneration
Keywords: AMD
Macular degeneration
non-central geographic atrophy
MTP-131
elamipretide
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2019-03-27
Enrollment: 176
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized, double-masked, placebo-controlled study to evaluate the safety, efficacy and pharmacokinetics of elamipretide in subjects with Age-Related Macular Degeneration with non-central Geographic Atrophy.

Detailed description: This was a randomized, double-masked, placebo controlled study using three periods to evaluate the safety, efficacy and pharmacokinetics of elamipretide in subjects with Age-Related Macular Degeneration with non-central Geographic Atrophy. The total duration of subject participation was up to 54 weeks, including a Screening Period (≤2 weeks), Treatment Period (48 weeks), and Follow-up (4 weeks). 176 eligible subjects were randomized in a 2:1 ratio (elamipretide:placebo) to receive 40 mg elamipretide or placebo. The study drug (i.e., elamipretide or placebo) was administered once daily via SC injection using the elamipretide delivery system during the 48 week Treatment Period. After completion of the 48-week Treatment Period subjects continued to be monitored for safety during the 4-week Follow-up Period and an end of study (EOS) Follow-up Visit was conducted at Week 52.

Eligibility criteria: Inclusion Criteria:

* Adults ≥ 55 years of age with at least 1 eye with AMD with non-central GA as determined by FAF.

Ocular conditions-study eye

* GA in the study eye at the Screening Visit may be multi-focal, but the cumulative GA lesion and size must:

  1. be ≥ 0.05 mm2 and ≤ 10.16 mm2 and
  2. reside completely within the FAF 30 or 35 degree image.
  3. must be at least 150 μm from foveal center with preserved outer retinal structural details
* No evidence of CNV by history, OCT or FA in the study eye.
* BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) score of ≥ 55 letters (Snellen equivalent ≥ 20/70) in the study eye at the Screening Visit and Baseline Visit.
* LL BCVA by ETDRS score of ≥ 10 letters in the study eye at the Screening Visit and Baseline Visit.
* LL VA deficit (defined as difference the between BCVA and LL BCVA) of \> 5 letters in the study eye at Screening and Baseline Visits.
* The fellow eye may have any of the following: no AMD, AMD without GA, AMD with GA, CNV AMD, or central GA. Ongoing treatment with anti-angiogenic therapies in the fellow eye is allowable.
* 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

Exclusion Criteria:

Ocular conditions-study eye

* The absence of observable hyper-FAF at the margins of the GA in the study eye(only for lesions ≥ 0.25mm2)
* 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.
* Presence or diagnosis of exudative AMD or CNV in the study eye.
* Presence of retinal vein occlusion in the study eye.
* Presence of diabetic retinopathy (a history of diabetes mellitus without retinopathy is not a criterion for exclusion) in either eye.
* Presence of vitreous hemorrhage in the study eye.
* History of retinal detachment in the study eye.
* History of macular hole (stages 2 to 4) in the study eye.
* Presence of an epiretinal membrane that causes distortion of the retinal contour in the study eye.
* Presence of vitreomacular traction in the study eye.
* At the Screening Visit, advanced glaucoma resulting in a cup to disc ratio of \> 0.8 in the study eye.
* History of glaucoma filtration surgery or uncontrolled glaucoma defined as IOP \> 22 mmHg at baseline despite anti-glaucoma treatment with or without topical anti-hypertensive eye drops in the study eye OR currently using \> 2 medications (note: combination medications count as 2 medications).
* Presence of visually significant cataract OR presence of significant posterior capsular opacity in the setting of pseudophakia. Significant cataract is defined as \> +2 nuclear sclerosis based upon the scale below or any Posterior Subcapsular Cataract in the study eye. The Sponsor, or its designee, will supply the trial sites with a copy of the standard photographs.
* 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.
* Ocular incisional or laser surgery (including cataract surgery) in the study eye within 90 days before Day 1.
* Yag laser capsulotomy in the study eye within 30 days before Day 1.
* Aphakia in the study eye.
* History of vitrectomy surgery, submacular surgery, or any vitreoretinal surgery in the study eye.
* Prior treatment with Visudyne® (verteporfin) ocular photodynamic therapy, external-beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy in the study eye.
* History of subthreshold laser treatment or other forms of photobiomodulation for AMD in the study eye.
* Intravitreal drug delivery in the past 60 days or 5-half-lives of the injected drug whichever is longer (e.g., intravitreal corticosteroid injection, anti angiogenic drugs, or device implantation) in the study eye.
* 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) from the Screening Visit through the completion of the trial.

Ocular conditions--either eye

* History of herpetic infection in either eye.
* Concurrent disease in either the study eye or fellow control eye that could require medical or surgical intervention during the study period.
* Active uveitis and/or vitritis (grade trace or above) in either eye.
* History of idiopathic or autoimmune-associated uveitis in either eye.
* Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.

Systemic conditions.

* Known to be immunocompromised or receiving systemic immunosuppression for ≥ 4 consecutive weeks prior to screening.
* Any disease or medical condition that in the opinion of the Investigator would prevent the subject from successfully participating in the study or might confound study results.

General

* Participation in other investigational drug or device clinical studies within 30 days of enrollment and/or planning to participate in any other investigational drug or device clinical studies within 30 days of study completion.
* History of allergy to fluorescein that is not amenable to treatment.
* Creatinine clearance of ≤ 30 mL/min at the Screening Visit (using Modification of Diet in Renal Disease Study formula).
* Inability to comply with study or follow-up procedures.
* Inability to obtain color fundus photograph, FAF, and FA of sufficient quality to be analyzed and interpreted.
* Active malignancy or any other cancer from which the subject has been cancer-free for \< 2 years.
* History of allergic reaction to the investigational drug or any of its components.
* Prior treatment with Elamipretide.

Primary outcomes:
measure: LL BCVA Score Change From Baseline
timeFrame: Baseline and Weeks 4, 8, 12, 24, 36, 48
measure: GA Area Change From Baseline by OCT
timeFrame: Baseline and Weeks 12, 24, 36, 48
Secondary outcomes:
measure: LL RA Change From Baseline
timeFrame: Baseline and Weeks 4,12, 36, 48
measure: BCVA Change From Baseline
timeFrame: Baseline and Weeks 4, 8, 12, 24, 36, 48
measure: GA Area as Measured by Fundus Autofluorescence (FAF) Change From Baseline
timeFrame: Baseline and Weeks 12, 24, 36, 48
Other outcomes:
measure: Macular Percentage of Ellipsoid Zone (EZ) Total Attenuation From Baseline
timeFrame: Baseline, Week 24 and Week 48
Locations:
city: Peoria
country: United States
facility: Associated Retina Consultants, Ltd.
state: Arizona
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Retina & Vitreous Consultants
state: Arizona
city: Phoenix
country: United States
facility: Retinal Research Institute, LLC
state: Arizona
city: Scottsdale
country: United States
facility: Global Retina Institute
state: Arizona
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Palm Desert
country: United States
facility: Retina Institute of California Medical Group
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Santa Maria
country: United States
facility: California Retina Consultants
state: California
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Miami
country: United States
facility: MedEye Associates
state: Florida
city: Palm Beach Gardens
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland valley retina consultants
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Springfield
country: United States
facility: New England Retina Consultants
state: Massachusetts
city: Jackson
country: United States
facility: Specialty Eye Institute
state: Michigan
city: Bloomfield
country: United States
facility: Retina Center of New Jersey LLC
state: New Jersey
city: Teaneck
country: United States
facility: New Jersey Retina
state: New Jersey
city: Rochester
country: United States
facility: Retina Associates of Western New York
state: New York
city: Durham
country: United States
facility: Duke Eye center
state: North Carolina
city: Cincinnati
country: United States
facility: Sterling Research Group
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Retina Northwest, P.C
state: Oregon
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Retina
state: Tennessee
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Retina Research Center, PLLC
state: Texas
city: Fort Worth
country: United States
facility: Ophthalmology Associates
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston, PA
state: Texas
city: Katy
country: United States
facility: Retina Consultants of Houston
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute, PA
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia, Department of Ophthalmology
state: Virginia
Study officials:
affiliation: Stealth BioTherapeutics
name: Sathyanarayana
role: STUDY_DIRECTOR
References: