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

• 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: Apellis Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Apellis Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: June 2, 2015
• First Posted Date: June 3, 2015
• Results First Submitted Date: August 4, 2020
• Results First Posted Date: October 6, 2020
• Last Update Posted Date: October 6, 2020
• Actual Study Start Date: January 28, 2015
• Actual Primary Completion Date: March 8, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: June 2, 2015): Number and severity of local and systemic adverse events. [ Time Frame: 0-90 Days ]

Current Secondary Outcome Measures (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 (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: 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)
• 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neovascular Age-Related Macular Degeneration

Intervention

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

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 2, 2016): 13
• Original Estimated Enrollment (submitted: June 2, 2015): 9
• Actual Study Completion Date: March 8, 2016
• Actual Primary Completion Date: March 8, 2016 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT02461771
• Other Study ID Numbers: POT-CP043014
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Apellis Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Apellis Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Federico Grossi, MD PhD; Apellis Pharmaceuticals, Inc.

• PRS Account: Apellis Pharmaceuticals, Inc.
• Verification Date: September 2020