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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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.

Study Type Interventional
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
Enrollment 13
Recruitment Details Male and female subjects aged at least 50 years with the presence of an active choroidal neovascular lesion secondary to age-related macular degeneration were recruited to this Phase 1 open-label, single-dose escalation study at 4 study centers in the United States and Australia.
Pre-assignment Details Subjects had received at least 3 anti-vascular endothelial growth factor treatments over the 26 week period prior to screening, and were enrolled into 1 of 3 cohorts to receive pegcetacoplan (previously known as APL-2). If both eyes were eligible for the study, the subject and Principal Investigator chose the eye that served as the study eye.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description 4 milligrams (mg) pegcetacoplan: Subjects received a single intravitreal (IVT) injection of pegcetacoplan (100 microliters [μL] of 40 mg per milliliter [mg/mL]) on Day 1. 10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1. 20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Period Title: Overall Study
Started 3 3 7
Completed [1] 3 3 7
Not Completed 0 0 0
[1]
Completed acute safety observation period (up to Day 15) and follow-up visits up to Day 113.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Total
Hide Arm/Group Description 4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1. 10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1. 20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1. Total of all reporting groups
Overall Number of Baseline Participants 3 3 7 13
Hide Baseline Analysis Population Description
The safety set included all subjects who received any amount of study drug.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 7 participants 13 participants
70
(60 to 73)
79
(74 to 81)
72
(68 to 93)
73
(60 to 93)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 13 participants
Female 1 2 5 8
Male 2 1 2 5
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 13 participants
White 3 3 7 13
Hispanic or Latino 0 1 2 3
Non-Hispanic or Latino 3 2 5 10
1.Primary Outcome
Title Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity
Hide Description Safety was assessed throughout the study. A TEAE was defined as any AE that started on/after the IVT injection of pegcetacoplan.
Time Frame Day 1 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set included all subjects who received any amount of study drug.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Measure Type: Count of Participants
Unit of Measure: Participants
All TEAEs 2 2 4
Ocular TEAEs 1 1 2
Treatment-related AEs 0 0 2
Serious AEs 0 0 0
TEAEs leading to discontinuation 0 0 0
2.Primary Outcome
Title Number of Dose Limiting Toxicities (DLTs)
Hide Description 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.
Time Frame Day 1 to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set included all subjects who received any amount of study drug.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Measure Type: Number
Unit of Measure: Number of DLTs
0 0 0
3.Primary Outcome
Title Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t])
Hide Description 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.
Time Frame Predose (screening), postdose Day 3 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification).
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Median (Full Range)
Unit of Measure: micrograms*day/milliliter (μg*day/mL)
11.89
(11.49 to 13.90)
29.95
(24.27 to 53.59)
69.53
(55.06 to 86.92)
4.Primary Outcome
Title Median Dose Normalized AUC(0-t)
Hide Description 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.
Time Frame Predose (screening), postdose Day 3 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification).
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Median (Full Range)
Unit of Measure: (μg*day/mL)/respective mg dose
2.97
(2.87 to 3.47)
3.00
(2.43 to 5.36)
3.48
(2.75 to 4.35)
5.Primary Outcome
Title Maximum Observed Serum Concentration (Cmax)
Hide Description The median Cmax is presented for each cohort.
Time Frame Predose (screening), postdose Day 3 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification).
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Median (Full Range)
Unit of Measure: μg/mL
0.383
(0.317 to 0.387)
0.764
(0.596 to 1.610)
2.140
(1.440 to 3.970)
6.Primary Outcome
Title Median Dose Normalized Cmax
Hide Description 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.
Time Frame Predose (screening), postdose Day 3 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification).
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Median (Full Range)
Unit of Measure: (μg/mL)/respective mg dose
0.096
(0.079 to 0.097)
0.076
(0.060 to 0.161)
0.107
(0.072 to 0.199)
7.Primary Outcome
Title Median Time to the Maximum Measured Serum Concentration (Tmax)
Hide Description 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.
Time Frame Predose (screening), postdose Day 3 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification).
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Median (Full Range)
Unit of Measure: day
14.0
(8.9 to 14.9)
7.9
(7.0 to 14.9)
15.0
(6.9 to 16.0)
8.Secondary Outcome
Title Median Change From Baseline in Visual Acuity for the Study Eye
Hide Description 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.
Time Frame Day 1 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy set included all subjects who received any amount of the study drug.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Median (Full Range)
Unit of Measure: letters read correctly
1
(0 to 4)
3
(-9 to 11)
-1
(-4 to 10)
9.Secondary Outcome
Title Median Change From Baseline in Central Retinal Thickness, Central Retinal Lesion Thickness and Central Subfield Thickness in the Study Eye
Hide Description Central retinal thickness, central retinal lesion thickness and central subfield thickness were determined using Spectral Domain Optical Coherence Tomography (SD-OCT).
Time Frame Day 1 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set included all subjects who received any amount of study drug.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Median (Full Range)
Unit of Measure: micrometers
Retinal thickness
-106
(-129 to 71.5)
5.0
(-109 to 22.0)
37.5
(-9.5 to 170.5)
Retinal lesion thickness
-79.5
(-128 to 64.0)
2.5
(-104 to 31.5)
19.0
(-21.5 to 212.0)
Central Subfield Thickness
-29.0
(-48.0 to 42.0)
-12.0
(-80.0 to 20.0)
65.0
(-11.0 to 138.0)
10.Secondary Outcome
Title Median Change From Baseline in Macular Cube Volume in the Study Eye
Hide Description Macular cube volume was determined using SD-OCT.
Time Frame Day 1 to Day 113
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set included all subjects who received any amount of study drug.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
Overall Number of Participants Analyzed 3 3 7
Median (Full Range)
Unit of Measure: mm^3
-0.4
(-2.1 to 0.2)
-0.1
(-0.3 to 0.2)
0.3
(-0.3 to 0.7)
Time Frame TEAEs were collected from Day 1 up to the final study visit at Day 113 (approximately 16 weeks).
Adverse Event Reporting Description The safety set included all subjects who received any amount of study drug.
 
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description 4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1. 10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1. 20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.
All-Cause Mortality
Cohort 1 Cohort 2 Cohort 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/3 (0.00%)      0/3 (0.00%)      0/7 (0.00%)    
Hide Serious Adverse Events
Cohort 1 Cohort 2 Cohort 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/3 (0.00%)      0/7 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1 Cohort 2 Cohort 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/3 (66.67%)      2/3 (66.67%)      4/7 (57.14%)    
Eye disorders       
Eye pain  1  1/3 (33.33%)  1 0/3 (0.00%)  0 2/7 (28.57%)  2
Foreign body sensation in eyes  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1
Retinal haemorrhage  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0
Vision blurred  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1
General disorders       
Pyrexia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1
Infections and infestations       
Hordeolum  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0
Urinary tract infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1
Musculoskeletal and connective tissue disorders       
Back pain  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0
Nervous system disorders       
Headache  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1
Renal and urinary disorders       
Albuminuria  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1
Skin and subcutaneous tissue disorders       
Pruritus  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  2
Skin irritation  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0
Vascular disorders       
Hypertension  1  1/3 (33.33%)  1 1/3 (33.33%)  1 0/7 (0.00%)  0
1
Term from vocabulary, MedDRA 17.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Apellis Clinical Trial Information Line
Organization: Apellis Pharmaceuticals, Inc
Phone: 1-833-284-6361
EMail: clinicaltrials@apellis.com
Layout table for additonal information
Responsible Party: Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02461771    
Other Study ID Numbers: POT-CP043014
First Submitted: June 2, 2015
First Posted: June 3, 2015
Results First Submitted: August 4, 2020
Results First Posted: October 6, 2020
Last Update Posted: October 6, 2020