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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03525613




Registration number
NCT03525613
Ethics application status
Date submitted
20/04/2018
Date registered
15/05/2018
Date last updated
6/07/2023

Titles & IDs
Public title
A Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration
Scientific title
A Phase 3, Multi-Center, Randomized, Double-Masked, Sham-Controlled Study to Compare the Efficacy and Safety of Intravitreal Pegcetacoplan Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)
Secondary ID [1] 0 0
APL2-304
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Geographic Atrophy 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APL-2
Treatment: Drugs - APL-2
Other interventions - Sham Procedure
Other interventions - Sham Procedure

Experimental: APL-2 15mg 0.1 mL Monthly for 24 months - A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every month

Experimental: APL-2 15mg 0.1 mL EOM for 24 months - A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every other month

Experimental: Sham Procedure Monthly for 24 months - Sham Procedure monthly for 24 months

Experimental: Sham Procedure Every Other Month for 24 months - Sham Procedure every other month for 24 months


Treatment: Drugs: APL-2
Complement (C3) Inhibitor

Treatment: Drugs: APL-2
Complement (C3) Inhibitor

Other interventions: Sham Procedure
Subjects will receive a Sham procedure every month

Other interventions: Sham Procedure
Subjects will receive a Sham procedure every other month
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12
Timepoint [1] 0 0
Baseline (screening) and Month 12
Secondary outcome [1] 0 0
LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24
Timepoint [1] 0 0
Baseline (screening) and Month 24
Secondary outcome [2] 0 0
Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24
Timepoint [2] 0 0
From Baseline (screening) through Month 24
Secondary outcome [3] 0 0
LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24
Timepoint [3] 0 0
Baseline (screening) and Month 24
Secondary outcome [4] 0 0
LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24
Timepoint [4] 0 0
Baseline (screening) and Month 24
Secondary outcome [5] 0 0
LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24
Timepoint [5] 0 0
Baseline (screening) and Month 24
Secondary outcome [6] 0 0
LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24
Timepoint [6] 0 0
Baseline (screening) and Month 24

Eligibility
Key inclusion criteria
The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria, the eye with the worst visual acuity at the screening visit will be designated as the study eye. If both eyes have the same visual acuity, the right eye will be selected as the study eye.

Ocular- specific inclusion criteria apply to the study eye only, unless otherwise specified.

* Age = 60 years.
* Normal Luminance best corrected visual acuity of 24 letters or better using Early Treatment Diabetic Retinopathy Study (ETDRS) charts (approximately 20/320 Snellen equivalent).
* Clinical diagnosis of GA of the macula secondary to AMD as determined by the Investigator and confirmed by the Reading Center.
* The GA lesion must meet the following criteria as determined by the central reading center's assessment of Fundus Autofluorescence (FAF) imaging at screening:

* Total GA area must be = 2.5 and = 17.5 mm2 (1 and 7 disk areas [DA] respectively)
* If GA is multifocal, at least one focal lesion must be = 1.25 mm2 (0.5 DA), with the overall aggregate area of GA, as specified above in 4a.
* The entire GA lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy.
* Presence of any pattern of hyperautofluorescence in the junctional zone of GA. Absence of hyperautofluorescence (i.e. pattern = none) is exclusionary.
* Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit the collection of good quality images as determined by the Investigator.
* Meets the following criteria related to microperimetry:

* Able to detect fixation target.
* Total elapsed time to complete the 10-2 68 point exam is = 30 minutes in duration.
* Reliability test ratio must be = 20%.
* Subject is willing and able to undertake microperimetry assessment in the opinion of the investigator.
* Female subjects must be:

* Women of non-child-bearing potential (WONCBP), or
* 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 and refrain from breastfeeding for the duration of the study.
* 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.
* Willing and able to give informed consent and to comply with the study procedures and assessments.
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified.

* GA secondary to a condition other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy in either eye.
* Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or an axial length >26 mm.
* Any history or active choroidal neovascularization (CNV), associated with AMD or any other cause, including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere based on SD-OCT imaging and/or fluorescein angiography as assessed by the Reading Center.
* Presence of an active ocular disease that in the opinion of the Investigator compromises or confounds visual function, including but not limited to, uveitis, other macular diseases (e.g. clinically significant epiretinal membrane (ERM), full thickness macular hole or uncontrolled glaucoma/ocular hypertension. Benign conditions in the opinion of the investigator such as peripheral retina dystrophy are not exclusionary).
* Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.
* History of laser therapy in the macular region.
* Aphakia or absence of the posterior capsule. Note: YAG laser posterior capsulotomy for posterior capsule opacification done at least 60 days prior to screening is not exclusionary.
* Any ocular condition other than GA secondary to AMD that may require surgery or medical intervention during the study period or, in the opinion of the Investigator, could compromise visual function during the study period.
* Any contraindication to IVT injection including current ocular or periocular infection.
* History of prior intravitreal injection.
* Unable to perform microperimetry reliably in the opinion of the investigator
* Prior participation in another interventional clinical study for intravitreal therapies in either eye (including subjects receiving sham).
* Prior participation in another interventional clinical study for geographic atrophy in either eye including investigational oral medication and placebo.
* Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (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.
* Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the 24-month treatment period unlikely, or would make the subject an unsafe study candidate.
* 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.
* Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to APL-2 or any of the excipients in APL-2 solution.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/06/2022
Sample size
Target
Accrual to date
Final
637
Recruitment in Australia
Recruitment state(s)
NSW,SA,South BlockWA
Recruitment hospital [1] 0 0
Marsden Eye Specialist - Parramatta
Recruitment hospital [2] 0 0
Adelaide Eye & Retina Clinic - Adelaide
Recruitment hospital [3] 0 0
Save Sight Institute - Sydney
Recruitment hospital [4] 0 0
Lions Eye Institute - Nedlands
Recruitment hospital [5] 0 0
Strathfield Retina Clinic - Strathfield
Recruitment hospital [6] 0 0
Sydney West Retina - Westmead
Recruitment postcode(s) [1] 0 0
2150 - Parramatta
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
2000 - Sydney
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment postcode(s) [5] 0 0
2135 - Strathfield
Recruitment postcode(s) [6] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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Colorado
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Connecticut
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Florida
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Georgia
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Illinois
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Indiana
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Kentucky
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Louisiana
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Maryland
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Massachusetts
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Michigan
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North Carolina
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Oregon
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Tennessee
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Wisconsin
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Brazil
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São Paulo
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Canada
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Ontario
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Praha
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Zlín
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France
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Créteil
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Lübeck
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Münster
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Haifa
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Jerusalem
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Roma
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Christchurch
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Rzeszów
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Madrir
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Belfast
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Liverpool
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Sunderland
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York

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Apellis Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a 24-month, Phase III, multicenter, randomized, double-masked, sham-injection controlled study to assess the efficacy and safety of multiple IVT injections of APL-2 in subjects with GA secondary to AMD.
Trial website
https://clinicaltrials.gov/study/NCT03525613
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03525613