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

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ClinicalTrials.gov Identifier: NCT02461771
Recruitment Status : Completed
First Posted : June 3, 2015
Results First Posted : October 6, 2020
Last Update Posted : October 6, 2020
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE June 2, 2015
First Posted Date  ICMJE June 3, 2015
Results First Submitted Date  ICMJE August 4, 2020
Results First Posted Date  ICMJE October 6, 2020
Last Update Posted Date October 6, 2020
Actual Study Start Date  ICMJE January 28, 2015
Actual Primary Completion Date March 8, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2020)
  • Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity [ Time Frame: Day 1 to Day 113 ]
    Safety was assessed throughout the study. A TEAE was defined as any AE that started on/after the IVT injection of pegcetacoplan.
  • Number of Dose Limiting Toxicities (DLTs) [ Time Frame: Day 1 to Day 15 ]
    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.
  • 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 ]
    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.
  • Median Dose Normalized AUC(0-t) [ Time Frame: Predose (screening), postdose Day 3 to Day 113 ]
    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.
  • Maximum Observed Serum Concentration (Cmax) [ Time Frame: Predose (screening), postdose Day 3 to Day 113 ]
    The median Cmax is presented for each cohort.
  • Median Dose Normalized Cmax [ Time Frame: Predose (screening), postdose Day 3 to Day 113 ]
    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.
  • Median Time to the Maximum Measured Serum Concentration (Tmax) [ Time Frame: Predose (screening), postdose Day 3 to Day 113 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 2, 2015)
Number and severity of local and systemic adverse events. [ Time Frame: 0-90 Days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2020)
  • Median Change From Baseline in Visual Acuity for the Study Eye [ Time Frame: Day 1 to Day 113 ]
    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.
  • 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 ]
    Central retinal thickness, central retinal lesion thickness and central subfield thickness were determined using Spectral Domain Optical Coherence Tomography (SD-OCT).
  • Median Change From Baseline in Macular Cube Volume in the Study Eye [ Time Frame: Day 1 to Day 113 ]
    Macular cube volume was determined using SD-OCT.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2015)
  • Exposure after single APL-2 intravitreal dose (AUC). [ Time Frame: 0-30 days ]
  • Maximum observed serum concentration (Cmax). [ Time Frame: 0-30 days ]
  • Time to maximum measured concentration (Tmax). [ Time Frame: 0-30 days ]
  • Terminal serum elimination half-life (t1/2). [ Time Frame: 0-30 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal Pegcetacoplan (APL-2) for Patients With Wet AMD
Official Title  ICMJE Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal APL-2 Therapy for Neovascular Age-Related Macular Degeneration (AMD)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neovascular Age-Related Macular Degeneration
Intervention  ICMJE Drug: Pegcetacoplan
On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.
Other Name: APL-2
Study Arms  ICMJE
  • Experimental: Pegcetacoplan Cohort 1
    4 mg of pegcetacoplan 100 μL IVT injection
    Intervention: Drug: Pegcetacoplan
  • Experimental: Pegcetacoplan Cohort 2
    10 mg of pegcetacoplan 100 μL IVT injection
    Intervention: Drug: Pegcetacoplan
  • Experimental: Pegcetacoplan Cohort 3
    20 mg of pegcetacoplan 100 μL IVT injection
    Intervention: Drug: Pegcetacoplan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 2, 2016)
13
Original Estimated Enrollment  ICMJE
 (submitted: June 2, 2015)
9
Actual Study Completion Date  ICMJE March 8, 2016
Actual Primary Completion Date March 8, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02461771
Other Study ID Numbers  ICMJE POT-CP043014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Apellis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Apellis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Federico Grossi, MD PhD Apellis Pharmaceuticals, Inc.
PRS Account Apellis Pharmaceuticals, Inc.
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP