Study of Pegcetacoplan (APL-2) Therapy in Patients With Geographic Atrophy

Geographic Atrophy Clinical Trial

— FILLY  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02503332
• Other study ID #: POT-CP121614
• Status: Completed
• Phase: Phase 2
• Start date: September 24, 2015
• Est. completion date: January 17, 2018

Study information

• Verified date: September 2020
• Source: Apellis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 246
• Est. completion date: January 17, 2018
• Est. primary completion date: July 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Geographic Atrophy

Intervention

Drug:
• Pegcetacoplan

Other:
• Sham Procedure

Locations

Country	Name	City	State
Australia	Royal Victorian Eye and Ear Hospital	East Melbourne	Victoria
Australia	Hobart eye Surgeons	Hobart	Tasmania
Australia	Center for Eye Research Australia	Melbourne	Victoria
Australia	Lions Eye Institute	Nedlands	Western Australia
Australia	Marsden Eye Specialists	Paramatta	New South Wales
Australia	Tasmanian Eye Institute	South Launceston	Tasmania
Australia	Save Sight Institute, Sydney Eye Hospital	Sydney	New South Wales
Australia	Sydney Retina Clinic and Day Surgery	Sydney	New South Wales
Australia	Sydney West Retina	Westmead	New South Wales
New Zealand	Southern Eye Specialists	Merivale	Christchurch
New Zealand	Auckland Eye	Remuera	Auckland
United States	Retina Research Institute of Texas	Abilene	Texas
United States	South East Retina	Augusta	Georgia
United States	Retina Research Center	Austin	Texas
United States	Elman Research	Baltimore	Maryland
United States	Retina Vitreous Asociates Mdical Goup	Beverly Hills	California
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Florida Eye Microsurgical Institute, Inc.	Boynton Beach	Florida
United States	Charlotte Eye Ear Nose and Throat Associates	Charlotte	North Carolina
United States	Cleveland Clinic Foundation/ Cole Eye Institute	Cleveland	Ohio
United States	Retina Associates of Cleveland	Cleveland	Ohio
United States	Duke University, Duke Eye Center	Durham	North Carolina
United States	Retina Health Center	Fort Myers	Florida
United States	Associated Retinal Consultants PC	Grand Rapids	Michigan
United States	Illinois Retina Associates	Harvey	Illinois
United States	Retina Consultants of Houston	Houston	Texas
United States	Midwest Eye Institute	Indianapolis	Indiana
United States	The Gavin Herbert Eye Institute/UC Irvine	Irvine	California
United States	University of Southern California - USC Eye Institute	Los Angeles	California
United States	Valley Retina Institute, PA	McAllen	Texas
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Retina Speciality Institute	Mobile	Alabama
United States	Tennessee Retina, PC	Nashville	Tennessee
United States	New England Retina Associates	New London	Connecticut
United States	Vitreous Retina Macula Consultants of New York	New York	New York
United States	Byers Eye Institute at Stanford, Stanford School of Medicine	Palo Alto	California
United States	Mid Atlantic	Philadelphia	Pennsylvania
United States	Retinal Research Institute	Phoenix	Arizona
United States	Retina Specialists	Plano	Texas
United States	Eyesight Opthalmic Services PA	Portsmouth	New Hampshire
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Utah	Salt Lake City	Utah
United States	Charlotte Eye Ear Nose and Throat Associates	Statesville	North Carolina
United States	Retina Consultants of Houston (The Woodlands)	The Woodlands	Texas
United States	Associated Retinal Consultants, PC	Traverse City	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Apellis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Least Square (LS) Mean Change From Baseline in Square Root GA Lesion Size in the Study Eye at Month 12	The square root GA lesion size (i.e. transformed area of GA) was measured by FAF photographs. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 12.
Primary	Number of Subjects With Treatment Emergent Adverse Events (TEAEs) in the Study Eye, Including by Severity	A TEAE was defined as any adverse event (AE) that commenced or worsened on or after time of first study drug administration up to 60 days beyond last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possibly related or probably related or not reported. Severity of TEAEs were categorized as mild; moderate; severe; life-threatening or death related to TEAE, according to Common Terminology Criteria for AEs v4.03. A TEAE of special interest (TEAESI) was defined as a TEAE of scientific and medical concern specific to pegcetacoplan, whether serious or non-serious.	From the time of first study drug administration (Day 1) up to Month 12 (Data cut-off date).
Secondary	LS Mean Change From Baseline in Untransformed GA Lesion Size in the Study Eye at Month 12	The untransformed area of GA was measured by FAF. Baseline is defined as the last available, non-missing observation prior to first study drug administration.	Baseline (Day 1) and Month 12.
Secondary	LS Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score of the Study Eye at Month 12	The BCVA letter score was determined using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. The score ranges from 0 to 100 letters, lower number indicating reduced visual acuity; a positive value of change from baseline indicates visual acuity gain and a negative value indicates visual acuity loss.	Baseline (Day 1) and Month 12.
Secondary	LS Mean Change From Baseline in Low Luminance BCVA (LL-BCVA) Score in the Study Eye at Month 12	The LL-BCVA was measured by placing a 2.0-log-unit neutral density filter over the best correction and having the participant read the normally illuminated ETDRS chart. The score ranges from 0 to 100 letters, lower number indicating worse vision; a positive value of change from baseline indicates visual acuity gain and a negative value indicates visual acuity loss.	Baseline (Day 1) and Month 12.
Secondary	LS Mean Change From Baseline in Low Luminance VA (LL-VA) Deficit Score in the Study Eye at Month 12	The LL-VA deficit score is calculated as BCVA score minus LL-BCVA score. The LL-VA deficit score ranges from 0 to 100 letters, lower number indicating worse deficit.	Baseline (Day 1) and Month 12.
Secondary	LS Mean Change From Baseline in Distance of GA Lesion From the Fovea (Foveal Encroachment) in the Study Eye at Month 12	The foveal encroachment in the study eye was measured by FAF. Baseline is defined as the last available, non-missing observation prior to first study drug administration.	Baseline (Day 1) and Month 12.
Secondary	Number of Subjects With Any Macular Neovascularization (MNV) TEAEs in the Study Eye	The number of subjects with any MNV TEAEs in the study eye was identified via clinical review of all ocular TEAEs.	From the time of first study drug administration (Day 1) up to Month 12 (Data cut-off date).