- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02461771
Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal Pegcetacoplan (APL-2) for Patients With Wet AMD (ASAP II)
September 11, 2020 updated by: Apellis Pharmaceuticals, Inc.
Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal APL-2 Therapy for Neovascular Age-Related Macular Degeneration (AMD)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
13
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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Parramatta, New South Wales, Australia, 2150
- Australia, New South Wells
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California
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Beverly Hills, California, United States, 90211
- United States, California
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Florida
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Miami, Florida, United States, 33136
- United States, Florida
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New Hampshire
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Portsmouth, New Hampshire, United States, 03801
- United States, New Hampshire
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Pegcetacoplan Cohort 1
4 mg of pegcetacoplan 100 μL IVT injection
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On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.
Other Names:
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Experimental: Pegcetacoplan Cohort 2
10 mg of pegcetacoplan 100 μL IVT injection
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On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.
Other Names:
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Experimental: Pegcetacoplan Cohort 3
20 mg of pegcetacoplan 100 μL IVT injection
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On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity
Time Frame: Day 1 to Day 113
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Safety was assessed throughout the study.
A TEAE was defined as any AE that started on/after the IVT injection of pegcetacoplan.
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Day 1 to Day 113
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Number of Dose Limiting Toxicities (DLTs)
Time Frame: Day 1 to Day 15
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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.
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Day 1 to Day 15
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Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t])
Time Frame: Predose (screening), postdose Day 3 to Day 113
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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.
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Predose (screening), postdose Day 3 to Day 113
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Median Dose Normalized AUC(0-t)
Time Frame: Predose (screening), postdose Day 3 to Day 113
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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.
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Predose (screening), postdose Day 3 to Day 113
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Maximum Observed Serum Concentration (Cmax)
Time Frame: Predose (screening), postdose Day 3 to Day 113
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The median Cmax is presented for each cohort.
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Predose (screening), postdose Day 3 to Day 113
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Median Dose Normalized Cmax
Time Frame: Predose (screening), postdose Day 3 to Day 113
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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.
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Predose (screening), postdose Day 3 to Day 113
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Median Time to the Maximum Measured Serum Concentration (Tmax)
Time Frame: Predose (screening), postdose Day 3 to Day 113
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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.
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Predose (screening), postdose Day 3 to Day 113
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Change From Baseline in Visual Acuity for the Study Eye
Time Frame: Day 1 to Day 113
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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.
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Day 1 to Day 113
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Median Change From Baseline in Central Retinal Thickness, Central Retinal Lesion Thickness and Central Subfield Thickness in the Study Eye
Time Frame: Day 1 to Day 113
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Central retinal thickness, central retinal lesion thickness and central subfield thickness were determined using Spectral Domain Optical Coherence Tomography (SD-OCT).
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Day 1 to Day 113
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Median Change From Baseline in Macular Cube Volume in the Study Eye
Time Frame: Day 1 to Day 113
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Macular cube volume was determined using SD-OCT.
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Day 1 to Day 113
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Federico Grossi, MD PhD, Apellis Pharmaceuticals, Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 28, 2015
Primary Completion (Actual)
March 8, 2016
Study Completion (Actual)
March 8, 2016
Study Registration Dates
First Submitted
June 2, 2015
First Submitted That Met QC Criteria
June 2, 2015
First Posted (Estimate)
June 3, 2015
Study Record Updates
Last Update Posted (Actual)
October 6, 2020
Last Update Submitted That Met QC Criteria
September 11, 2020
Last Verified
September 1, 2020
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- POT-CP043014
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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