Clinical trial NCT02503332: Study of Pegcetacoplan (APL-2) Therapy in Patients With Geographic Atrophy
Official title: A Phase II, Multicenter, Randomized, Single-Masked, Sham-Controlled Study of Safety, Tolerability and Evidence of Activity of Intravitreal APL-2 Therapy in Patients With Geographic Atrophy (GA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Geographic Atrophy
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-20
Enrollment: 246
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study are to assess the safety, tolerability and evidence of activity of multiple intravitreal (IVT) injections of pegcetacoplan in subjects with Geographic Atrophy associated with Age-Related Macular Degeneration (AMD).

Detailed description: This is a Phase II, prospective, multicenter, randomized, single-masked, sham-controlled study to assess the safety, tolerability and evidence of activity of multiple IVT injections of pegcetacoplan in subjects with GA secondary to Age-Related Macular Degeneration.

The study will randomize approximately 240 subjects to obtain at least 200 evaluable subjects across 40 multinational sites.

Subjects will be randomized in a 2:2:1:1 manner to receive pegcetacoplan Monthly (AM), pegcetacoplan Every-Other-Month (AEOM), Sham injection Monthly (SM) or Sham injection Every-Other-Month (SEOM), respectively.

All subjects will return to the clinical site on Day 7 to assess acute safety after the first injection. After that, subjects in the monthly groups will return to the clinical site for additional pegcetacoplan (or Sham) injections and study procedures every month until Month 12. Subjects in the Every-Other-Month groups will return to the clinical site for additional pegcetacoplan (or Sham) injections and study procedures every two months until Month 12. All subjects will return for follow-up visits on Months 15 and 18 (3 and 6 months after last injection, respectively).

Eligibility criteria: Inclusion Criteria: Unless specified otherwise, ocular specific inclusion criteria apply to the study eye only.

1. Male or Female.
2. Age greater than or equal to 50 years.
3. BCVA of 20/320 (Snellen equivalent) or better using ETDRS charts.
4. Diagnosis of GA of the macula secondary to age-related macular degeneration, confirmed within 14 days prior to randomization by the central reading center (CRC) using Fundus Autofluorescence (FAF) images, as well as the following criteria:

   1. Total GA area must be ≥ 2.5 and ≤ 17.5 mm2 (1 and 7 disk areas \[DA\] respectively), determined by screening images of FAF.
   2. If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA).
   3. GA can be completely visualized on the macula centered image.
   4. GA must be able to be photographed in its entirety.
   5. GA must be able to be measured separately from any areas of peripapillary atrophy as assessed by the CRC.
   6. Presence of any pattern of hyperautofluorescence in the junctional zone of GA. Absence of hyperautoflouorescence (i.e. pattern = none) is exclusionary. See Holz et al. 2007.1
5. Female subjects must be:

   1. Women of non-child-bearing potential (WONCBP), or
   2. Women of child-bearing potential (WOCBP) with a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study.
6. Males with female partners of child-bearing potential must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study.
7. Willing and able to give informed consent.

Exclusion Criteria: Unless specified otherwise, ocular specific inclusion criteria apply to the study eye only.

1. GA due to causes other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy.
2. Spherical equivalent of the refractive error demonstrating \> 6 diopters of myopia or an axial length \>26 mm.
3. Any history or current evidence of exudative ("wet") AMD including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere in the retina based on fluorescein angiogram as assessed by the CRC.
4. Retinal disease other than AMD; however, benign conditions of the vitreous or peripheral retina are not exclusionary (i.e. pavingstone degeneration).
5. Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the Investigator interferes with ophthalmologic examination (e.g. advanced cataract or corneal abnormalities).
6. Any ophthalmologic condition that prevents adequate imaging of the retina judged by the site or CRC.
7. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.
8. Aphakia or absence of the posterior capsule. Previous violation of the posterior capsule is also excluded unless it occurred as a result of yttrium aluminum garnet (YAG) laser posterior capsulotomy in association with prior posterior chamber intraocular lens implantation and at least 60 days prior to Day 0.
9. Any ophthalmic condition that may require surgery during the study period.
10. Any contraindication to IVT injection including current ocular or periocular infection.
11. History of uveitis or endophthalmitis.
12. History of IVT injection at any time.
13. Participation in another interventional clinical study, or use of any experimental treatment for AMD or any other investigational new drug within 6 weeks or 5 half-lives of the active (whichever is longer) prior to the start of study treatment. Note: clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary.
14. Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the treatment period unlikely, or in general a poor medical risk because of other systemic diseases or active uncontrolled infections.
15. Any screening laboratory value (hematology, serum chemistry or urinalysis) that in the opinion of the Investigator is clinically significant and not suitable for study participation.
16. Hypersensitivity to fluorescein.

Primary outcomes:
measure: Least Square (LS) Mean Change From Baseline in Square Root GA Lesion Size in the Study Eye at Month 12
timeFrame: Baseline (screening) and Month 12.
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) in the Study Eye, Including by Severity
timeFrame: From the time of first study drug administration (Day 1) up to Month 12 (Data cut-off date).
Secondary outcomes:
measure: LS Mean Change From Baseline in Untransformed GA Lesion Size in the Study Eye at Month 12
timeFrame: Baseline (Day 1) and Month 12.
measure: LS Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score of the Study Eye at Month 12
timeFrame: Baseline (Day 1) and Month 12.
measure: LS Mean Change From Baseline in Low Luminance BCVA (LL-BCVA) Score in the Study Eye at Month 12
timeFrame: Baseline (Day 1) and Month 12.
measure: LS Mean Change From Baseline in Low Luminance VA (LL-VA) Deficit Score in the Study Eye at Month 12
timeFrame: Baseline (Day 1) and Month 12.
measure: LS Mean Change From Baseline in Distance of GA Lesion From the Fovea (Foveal Encroachment) in the Study Eye at Month 12
timeFrame: Baseline (Day 1) and Month 12.
measure: Number of Subjects With Any Macular Neovascularization (MNV) TEAEs in the Study Eye
timeFrame: From the time of first study drug administration (Day 1) up to Month 12 (Data cut-off date).
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Retina Speciality Institute
state: Alabama
city: Phoenix
country: United States
facility: Retinal Research Institute
state: Arizona
city: Beverly Hills
country: United States
facility: Retina Vitreous Asociates Mdical Goup
state: California
city: Irvine
country: United States
facility: The Gavin Herbert Eye Institute/UC Irvine
state: California
city: Los Angeles
country: United States
facility: University of Southern California - USC Eye Institute
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute at Stanford, Stanford School of Medicine
state: California
city: New London
country: United States
facility: New England Retina Associates
state: Connecticut
city: Boynton Beach
country: United States
facility: Florida Eye Microsurgical Institute, Inc.
state: Florida
city: Fort Myers
country: United States
facility: Retina Health Center
state: Florida
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Augusta
country: United States
facility: South East Retina
state: Georgia
city: Harvey
country: United States
facility: Illinois Retina Associates
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: Baltimore
country: United States
facility: Elman Research
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Grand Rapids
country: United States
facility: Associated Retinal Consultants PC
state: Michigan
city: Traverse City
country: United States
facility: Associated Retinal Consultants, PC
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Portsmouth
country: United States
facility: Eyesight Opthalmic Services PA
state: New Hampshire
city: New York
country: United States
facility: Vitreous Retina Macula Consultants of New York
state: New York
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose and Throat Associates
state: North Carolina
city: Durham
country: United States
facility: Duke University, Duke Eye Center
state: North Carolina
city: Statesville
country: United States
facility: Charlotte Eye Ear Nose and Throat Associates
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation/ Cole Eye Institute
state: Ohio
city: Cleveland
country: United States
facility: Retina Associates of Cleveland
state: Ohio
city: Philadelphia
country: United States
facility: Mid Atlantic
state: Pennsylvania
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Retina, PC
state: Tennessee
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute, PA
state: Texas
city: Plano
country: United States
facility: Retina Specialists
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Houston (The Woodlands)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Paramatta
country: Australia
facility: Marsden Eye Specialists
state: New South Wales
city: Sydney
country: Australia
facility: Save Sight Institute, Sydney Eye Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Retina Clinic and Day Surgery
state: New South Wales
city: Westmead
country: Australia
facility: Sydney West Retina
state: New South Wales
city: Hobart
country: Australia
facility: Hobart eye Surgeons
state: Tasmania
city: South Launceston
country: Australia
facility: Tasmanian Eye Institute
state: Tasmania
city: East Melbourne
country: Australia
facility: Royal Victorian Eye and Ear Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Center for Eye Research Australia
state: Victoria
city: Nedlands
country: Australia
facility: Lions Eye Institute
state: Western Australia
city: Remuera
country: New Zealand
facility: Auckland Eye
state: Auckland
city: Merivale
country: New Zealand
facility: Southern Eye Specialists
state: Christchurch
Study officials:
affiliation: Apellis Pharmaceuticals, Inc.
name: Federico Grossi, MD PhD
role: STUDY_DIRECTOR
References:
citation: Vogl WD, Riedl S, Mai J, Reiter GS, Lachinov D, Bogunovic H, Schmidt-Erfurth U. Predicting Topographic Disease Progression and Treatment Response of Pegcetacoplan in Geographic Atrophy Quantified by Deep Learning. Ophthalmol Retina. 2023 Jan;7(1):4-13. doi: 10.1016/j.oret.2022.08.003. Epub 2022 Aug 7.
citation: Liao DS, Metlapally R, Joshi P. Pegcetacoplan treatment for geographic atrophy due to age-related macular degeneration: a plain language summary of the FILLY study. Immunotherapy. 2022 Sep;14(13):995-1006. doi: 10.2217/imt-2022-0078. Epub 2022 Jul 21.
citation: Nittala MG, Metlapally R, Ip M, Chakravarthy U, Holz FG, Staurenghi G, Waheed N, Velaga SB, Lindenberg S, Karamat A, Koester J, Ribeiro R, Sadda S. Association of Pegcetacoplan With Progression of Incomplete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration: A Post Hoc Analysis of the FILLY Randomized Clinical Trial. JAMA Ophthalmol. 2022 Mar 1;140(3):243-249. doi: 10.1001/jamaophthalmol.2021.6067.