Clinical trial NCT02848313: An Open-Label, Phase 1 Clinical Study to Evaluate the Safety and Tolerability of Subcutaneous Elamipretide in Subjects With Intermediate Age-Related Macular Degeneration
Official title: An Open-Label, Phase 1 Clinical Study to Evaluate the Safety and Tolerability of Subcutaneous Elamipretide in Subjects With Intermediate Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Age-Related Macular Degeneration
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-28
Enrollment: 40
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Both arms received 40 mg dose of elamipretide administered once daily as a 1.0mL SC injection.
Primary purpose: TREATMENT

Brief summary: This is an open-label, Phase 1 single-center study in approximately 40 subjects who have 1 eye with intermediate AMD, including a high-risk drusen without geographic atrophy (GA) subgroup and a noncentral GA subgroup. Eligible subjects will receive 40 mg of elamipretide administered as a once daily 1.0 mL subcutaneous injection for 12 weeks.


Eligibility criteria: Inclusion Criteria:

For this study, only 1 eye of an eligible subject will be included and designated as the study eye. However, all specified ophthalmic testing will be performed on both eyes at each time point. A potential subject must meet the following criteria to be eligible for inclusion in the study:

Intermediate AMD - noncentral GA disease group:

1. Adults ≥ 55 years of age with 1 eye with intermediate AMD - noncentral GA.
2. No evidence of choroidal neovascularization (active or prior history) in the study eye.
3. Geographic atrophy may be multifocal, but the cumulative GA lesion size must be:

   1. ≥ 1.27 mm2 (approximately ≥ 0.5 DA) and ≤ 10.16 mm2 (approximately ≤ 4 DA).
   2. Must reside completely within the FAF imaging field (field 2 to 30-degree image centered on the fovea).
4. Presence of measurable hyperautofluorescence adjacent to the discrete foci of GA.

   OR

   Intermediate AMD - high-risk drusen without GA disease group:
5. ≥ 55 years of age with one eye with intermediate AMD - high-risk drusen without GA.
6. High-risk drusen is defined as presence of either at least 1 large (≥ 125 µm) druse or multiple medium-size (between 63 and 124 µm) drusen.

   General (both disease groups):
7. Able to provide informed consent and willing to comply with all study visits and examinations.
8. Women of childbearing potential who are not pregnant or nursing and have a negative serum pregnancy test at screening.
9. Best-corrected visual acuity assessed by ETDRS letters ≥ 55 letters (Snellen equivalent ≥ 20/70).
10. Low-luminance visual acuity deficit (defined as difference between BCVA and LL visual acuity) \> 5 letters.
11. Has at least two Low-Luminance Questionnaire sub scale results, in which one of the abnormal subscales is either general dim light vision or dim light reading.
12. The fellow eye may have intermediate AMD without noncentral GA (i.e., high-risk drusen), intermediate AMD with noncentral GA, NV AMD, or central GA. Ongoing treatment with antiangiogenic therapies in the fellow eye is allowable.
13. No evidence of visually significant cataract OR pseudophakia without evidence of posterior capsular opacity.
14. Sufficiently clear ocular media, adequate pupillary dilation, fixation to permit quality fundus imaging, and able to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment.
15. Able to administer SC study drug solution as demonstrated at screening or able to have a care provider or appropriate designee who can administer the study drug (i.e., a capable family member or home health nursing aide).
16. If of childbearing potential or in a relationship with a partner of childbearing potential, are able to abstain from sex or use acceptable contraception during the study and for 3 months after dosing.

    1. For men: Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the subject. The subject also agrees to use an acceptable method of contraception should they become sexually active. Subjects must use a condom with spermicide from the date of informed consent until at least 3 months after the last dose of study drug. Periodic abstinence (e.g.calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
    2. For women: abstinence is only acceptable when it is in line with the preferred and usual lifestyle of the subject. The subject agrees to use an acceptable method of contraception should they become sexually active. Maintenance of a monogamous relationship with a male partner who has been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days before the Screening visit or confirmed via sperm analysis), 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 are acceptable methods.
17. Ability and willingness to undertake all scheduled visits and assessments.

Exclusion Criteria:

A subject with study eye who meets any of the following criteria will be excluded from the study:

Ocular conditions - study eye

1. Age-related macular degeneration with any evidence of central GA (i.e., involving the fovea).
2. Atrophic retinal disease because of causes other than AMD.
3. Presence or diagnosis of exudative AMD or choroidal neovascularization in the study eye.
4. History of diabetic retinopathy (a history of diabetes mellitus without retinopathy is not a criterion for exclusion).
5. Presence of vitreous hemorrhage.
6. History of retinal detachment or macular hole (stage 3 or 4) in the study eye.
7. Presence of macular pucker.
8. History of uncontrolled glaucoma, defined as advanced cup-to-disc ratio \> 0.7 and IOP \> 25, with or without topical antihypertensive eye drops; treatment of ocular hypertension or controlled glaucoma are not criteria for exclusion.
9. History of advanced guttae indicative of Fuchs endothelial dystrophy.
10. Presence of visually significant cataract OR presence of significant posterior capsular opacity in the setting of Pseudophakia.
11. Presence of significant keratopathy that would cause scattering of light or alter visual function, especially in LL conditions.
12. Ocular incisional surgery (including cataract surgery) in the study eye within 3 months (i.e. 90 days) before Day 1.
13. Aphakia.
14. History of vitrectomy surgery, submacular surgery, or any vitreoretinal surgery.
15. Prior treatment with Visudyne ® (verteporfin), external-beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy.
16. History of prophylactic subthreshold laser treatment for retinal disease.
17. Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection, anti-angiogenic drugs, or device implantation) in the study eye.

    Ocular conditions - either eye
18. Active uveitis and/or vitritis (grade trace or above) in either eye.
19. History of idiopathic or autoimmune-associated uveitis in either eye.
20. Active, infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.

    Systemic conditions
21. Known to be immunocompromised or receiving systemic immunosuppression.
22. Any disease or medical condition that in the opinion of the Investigator would prevent the subject from participating in the study or might confound study results.
23. Estimated glomerular filtration rate \< 30 mL/minute, by MDRD.
24. Presence or history of clinically significant allergy disease requiring treatment, as judged by the Investigator. Hay fever is allowed unless it is active.

    General
25. Participation in other investigational drug or device clinical trials within 30 days before enrollment, or planning to participate in any other investigational drug or device clinical trials within 30 days of study completion.
26. History of allergy to fluorescein that is not amenable to treatment.
27. Inability to comply with study or follow-up procedures.
28. Inability to obtain color fundus photograph, FAF, and fluorescein angiography of sufficient quality to be analyzed and interpreted.
29. History of allergic reaction to the investigational drug or any of its components.
30. Current use of or likely need for any excluded medication.

Primary outcomes:
measure: Change From Baseline in Mean Standard Luminance Best-corrected Visual Acuity (BCVA)
timeFrame: Day 0 (Baseline to Day 7, and to Weeks 4, 8, 12, 16, 20, 24, and 28.
Secondary outcomes:
measure: Change From Baseline in Mean Low Luminance Best-Corrected Visual Acuity (LLBCVA)
timeFrame: Baseline to Day 7, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 28.
measure: Change From Baseline in Mean Dark Adaptometry
timeFrame: Baseline (Day 0) and Week 24
measure: Mean Treatment Compliance (%) of Administration of Subcutaneous Elamipretide
timeFrame: Baseline through Week 28
measure: Mean Number of Home Health Visits to Administer Elamipretide
timeFrame: Baseline (Day 0) through Week 24
measure: Change From Baseline in Mean Area of Geographic Atrophy by Fundus Autofluorescence
timeFrame: Baseline (Day 0) to Week 24
measure: Change From Baseline in Mean Area of Geographic Atrophy as Measured by Spectral-Domain Optical Coherence Tomography (SD-OCT)
timeFrame: Baseline to Week 24
measure: Change From Baseline in Mean Reading Acuity Test: With Standard Luminance
timeFrame: Baseline and Weeks 4, 8, 12, 16 20, 24 and 28
measure: Change From Baseline in Mean Reading Acuity Test: Low Luminance
timeFrame: Assessed at screening, baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 28
measure: Change From Baseline in National Eye Institute Visual Function Questionnaire-39 (VFQ-39) Score Standard Luminance
timeFrame: Assessed at baseline (Day 0), Week 12, Week 24 and Week 28
measure: Change From Baseline in Mean Low Luminance Questionnaire (LLQ) Score
timeFrame: Baseline (Day 0), Week 12, and Week 24 and Week 28
measure: Change From Baseline in Mean Mesopic Light Sensitivity
timeFrame: Baseline (Day 0) and Weeks 4,8,12,16,20,and 24
measure: Change From Baseline in Mean Retinal Pigment Epithelium - Drusen Complex (RPEDC) Thickness as Measured by SD-OCT
timeFrame: Baseline (Day 0) and Week 24
measure: Change From Baseline in Mean Retinal Pigment Epithelium-Drusen Complex Volume
timeFrame: Baseline (Day 0) to Week 24
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University School of Medicine / Dept. of Ophthalmology (Duke Eye Center)
state: North Carolina
Study officials:
affiliation: Duke University School of Medicine / Dept. of Ophthalmology (Duke Eye Center)
name: Scott W Cousins, MD
role: PRINCIPAL_INVESTIGATOR
References: