Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal Pegcetacoplan (APL-2) for Patients With Wet AMD

Study Overview
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Brief Summary
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The objective of this study is to provide initial safety, tolerability and pharmacokinetics information of intravitreal administration of pegcetacoplan in order to support further development into larger Phase II studies for treatment of patients with AMD.

Official Title
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Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal APL-2 Therapy for 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: Male or Female Age ≥ 50 years The presence of an active choroidal neovascular lesion secondary to AMD On treatment with anti-VEGF therapy (Lucentis®, Eylea® or Avastin®) Must have received at least 3 anti-VEGF treatments over the 26-week period prior to screening (Screening Visit) Evidence that the macular fluid has responded to anti-VEGF in the past based on OCT in the opinion of PI At screening, evidence of subretinal fluid and retinal cystic changes Must have received anti-VEGF treatment within 10 days prior to pegcetacoplan treatment (anti-VEGF can be administered on the same day of the screening visit after the screening procedures have been completed) OCTs of sufficient quality to allow for the assessment of the central macular fluid can be obtained 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 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 Exclusion Criteria: Choroidal neovascularization associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc Decreased vision due to retinal disease not attributable to choroidal neovascularization, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis or epiretinal membrane, a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar drusen), idiopathic parafoveal telangiectasis, or central serous retinopathy Additional ocular diseases that have irreversibly compromised or, during follow-up, could likely compromise the VA of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non proliferative diabetic retinopathy, or proliferative diabetic retinopathy Decreased vision due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina Cataract surgery within three months of enrollment Presence of any hemorrhage History of treatment for CNV: Previous PDT treatment within 30 days prior to enrollment in the study Previous extrafoveal or juxtafoveal thermal laser photocoagulation within 30 days prior to enrollment in the study Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization Medical problems that make consistent follow-up over the treatment period unlikely (e.g. stroke, severe MI, end stage malignancy), or in general a poor medical risk because of other systemic diseases or active uncontrolled infections Hypersensitivity to fluorescein

Ages Eligible for Study
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Minimum Age: 50 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegcetacoplan Cohort 1<br>4 mg of pegcetacoplan 100 μL IVT injection | Drug: Pegcetacoplan<br>* On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.<br>* Other names: APL-2;|
| Experimental: Pegcetacoplan Cohort 2<br>10 mg of pegcetacoplan 100 μL IVT injection | Drug: Pegcetacoplan<br>* On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.<br>* Other names: APL-2;|
| Experimental: Pegcetacoplan Cohort 3<br>20 mg of pegcetacoplan 100 μL IVT injection | Drug: Pegcetacoplan<br>* On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.<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 Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity | Safety was assessed throughout the study. A TEAE was defined as any AE that started on/after the IVT injection of pegcetacoplan. | Day 1 to Day 113 | 
| Number of Dose Limiting Toxicities (DLTs) | The occurrence of any of the following AEs were considered DLTs: intraocular inflammation (vitritis or uveitis), endophthalmitis, sustained elevation of intraocular pressure ≥30 millimeters (mm) of mercury, and/or sustained loss of visual acuity ≥15 letters not attributable to the injection procedure or progression of disease. | Day 1 to Day 15 | 
| Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t]) | The AUC(0-t) was measured using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing. The median AUC(0-t) is presented for each cohort. | Predose (screening), postdose Day 3 to Day 113 | 
| Median Dose Normalized AUC(0-t) | The AUC(0-t) was measured using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing. The dose normalized AUC(0-t) was calculated for each subject by dividing the parameter by the subject's respective dose in milligrams. The median dose normalized AUC(0-t) is presented for each cohort. | Predose (screening), postdose Day 3 to Day 113 | 
| Maximum Observed Serum Concentration (Cmax) | The median Cmax is presented for each cohort. | Predose (screening), postdose Day 3 to Day 113 | 
| Median Dose Normalized Cmax | The dose normalized Cmax was calculated for each subject by dividing the parameter by the subject's respective dose in milligrams. The median dose normalized Cmax is presented for each cohort. | Predose (screening), postdose Day 3 to Day 113 | 
| Median Time to the Maximum Measured Serum Concentration (Tmax) | The median Tmax is presented for each cohort. If the maximum value occurred at more than 1 time point, Tmax was defined as the first time point with this value. | Predose (screening), postdose Day 3 to Day 113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Change From Baseline in Visual Acuity for the Study Eye | Best Corrected Visual Acuity (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. | Day 1 to Day 113 | 
| Median Change From Baseline in Central Retinal Thickness, Central Retinal Lesion Thickness and Central Subfield Thickness in the Study Eye | Central retinal thickness, central retinal lesion thickness and central subfield thickness were determined using Spectral Domain Optical Coherence Tomography (SD-OCT). | Day 1 to Day 113 | 
| Median Change From Baseline in Macular Cube Volume in the Study Eye | Macular cube volume was determined using SD-OCT. | Day 1 to Day 113 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, Wet AMD, Neovascular AMD