Pegcetacoplan (APL-2) in Neovascular AMD

Study Overview
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Brief Summary
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Safety Assessment of Pegcetacoplan in Patients with Neovascular AMD

Official Title
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An 18-Month Phase Ib/II Multi-Center, Open Label Study to Evaluate the Safety of Intravitreal APL-2 Therapy in Patients With Neovascular Age-Related Macular Degeneration (AMD)

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Pegcetacoplan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 60 years. Normal Luminance best corrected visual acuity (NL-BCVA) of 24 letters or better using Early Treatment Diabetic Retinopathy Study (ETDRS) charts (20/320 Snellen equivalent). Clinical diagnosis of neovascular AMD with the following criteria met: Eligible for an injection of an anti-VEGF injection with macular fluid present at Day -28. Must have been treated with anti-VEGF in study eye for at least 6 months prior to joining the study. At least 6 months of intravitreal anti-VEGF therapy at intervals not greater than 8 weeks (± 7 days) for the past 2 injections in the eye that is selected to be the study eye. A clinically meaningful (50%) reduction in excess macular fluid or macular thickness in the study eye at the discretion of the investigator between Screening Day -28 and Screening Day -14 as assessed by SD-OCT. 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 Exclusion Criteria: Presence of other causes of choroidal neovascularization (CNV) including pathologic myopia (spherical equivalent ≥ -6 diopters), central serous chorioretinopathy, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis. History of vitrectomy to the study eye Presence of 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). Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization. Any history of endophthalmitis. Trabeculectomy or aqueous shunt or valve in the study eye. Aphakia or absence of the posterior capsule. Note: 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 baseline. Any ophthalmic condition 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 (e.g. severe uncontrolled glaucoma, clinically significant diabetic macular edema, ischemic optic neuropathy, retinal vasculopathies). Any contraindication to IVT injection including current ocular or periocular infection. Current treatment for active systemic or localized infection. Participation in any systemic experimental treatment or any other systemic 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 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 baseline 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 pegcetacoplan or any of the excipients in pegcetacoplan solution

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegcetacoplan Study Drug<br> | Drug: Pegcetacoplan<br>* Study Drug<br>* Other names: APL-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | TEAEs were defined as those adverse events (AEs) that developed or worsened after the first dose of study drug, up to 30 days after the last dose. The severity of the TEAEs was classified as mild (asymptomatic/mild symptoms); moderate (minimal, local/non-invasive intervention indicated); severe (medically significant but not life-threatening); life-threatening or leading to death. The number of subjects experiencing 1 TEAE in each category is presented. A maximum of 7 injections of pegcetacoplan (per subject) and a maximum of 13 injections of anti-VEGF (per subject) were received during the study. | Day 1 up to end of study (up to 1 year). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | The CST was measured using SD-OCT throughout the study and the mean change from baseline at each timepoint is presented for the study eye. | Day 1 up to Day 360 (12 months). | 
| Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters | Physical examinations, vital signs and laboratory parameters were monitored throughout the study and any subjects showing a clinically significant change from baseline over the study period are presented. | Baseline (Screening or Day 1) up to end of study (up to 1 year). |