Clinical trial NCT02461771: Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal Pegcetacoplan (APL-2) for Patients With Wet AMD
Official title: Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal APL-2 Therapy for Neovascular Age-Related Macular Degeneration (AMD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neovascular Age-Related Macular Degeneration
Keywords: AMD
Wet AMD
Neovascular AMD
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-03
Enrollment: 13
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Male or Female
2. Age ≥ 50 years
3. The presence of an active choroidal neovascular lesion secondary to AMD
4. On treatment with anti-VEGF therapy (Lucentis®, Eylea® or Avastin®)
5. Must have received at least 3 anti-VEGF treatments over the 26-week period prior to screening (Screening Visit)
6. Evidence that the macular fluid has responded to anti-VEGF in the past based on OCT in the opinion of PI
7. At screening, evidence of subretinal fluid and retinal cystic changes
8. 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)
9. OCTs of sufficient quality to allow for the assessment of the central macular fluid can be obtained
10. 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
11. 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
12. Willing and able to give informed consent

Exclusion Criteria:

1. Choroidal neovascularization associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc
2. 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
3. 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
4. Decreased vision due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina
5. Cataract surgery within three months of enrollment
6. Presence of any hemorrhage
7. History of treatment for CNV:

   1. Previous PDT treatment within 30 days prior to enrollment in the study
   2. Previous extrafoveal or juxtafoveal thermal laser photocoagulation within 30 days prior to enrollment in the study
8. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization
9. 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
10. Hypersensitivity to fluorescein

Primary outcomes:
measure: Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity
timeFrame: Day 1 to Day 113
measure: Number of Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 to Day 15
measure: Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t])
timeFrame: Predose (screening), postdose Day 3 to Day 113
measure: Median Dose Normalized AUC(0-t)
timeFrame: Predose (screening), postdose Day 3 to Day 113
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: Predose (screening), postdose Day 3 to Day 113
measure: Median Dose Normalized Cmax
timeFrame: Predose (screening), postdose Day 3 to Day 113
measure: Median Time to the Maximum Measured Serum Concentration (Tmax)
timeFrame: Predose (screening), postdose Day 3 to Day 113
Secondary outcomes:
measure: Median Change From Baseline in Visual Acuity for the Study Eye
timeFrame: Day 1 to Day 113
measure: Median Change From Baseline in Central Retinal Thickness, Central Retinal Lesion Thickness and Central Subfield Thickness in the Study Eye
timeFrame: Day 1 to Day 113
measure: Median Change From Baseline in Macular Cube Volume in the Study Eye
timeFrame: Day 1 to Day 113
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: United States, California
state: California
city: Miami
country: United States
facility: United States, Florida
state: Florida
city: Portsmouth
country: United States
facility: United States, New Hampshire
state: New Hampshire
city: Parramatta
country: Australia
facility: Australia, New South Wells
state: New South Wales
Study officials:
affiliation: Apellis Pharmaceuticals, Inc.
name: Federico Grossi, MD PhD
role: STUDY_DIRECTOR
References: