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A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH

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: NCT03593200
Recruitment Status : Completed
First Posted : July 20, 2018
Results First Posted : December 22, 2020
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition PNH
Intervention Drug: Pegcetacoplan
Enrollment 4
Recruitment Details This Phase 2a, open-label, multiple-dose study was conducted in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who had not received treatment with eculizumab (Soliris®) in the past, between 16 August 2018 and 22 October 2019.
Pre-assignment Details Up to 20 subjects were planned to be enrolled; however, the sponsor decided to close recruitment after 4 subjects were enrolled based on the conclusion that sufficient data were collected to meet the study objectives.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description Subjects received subcutaneous (SC) infusions of pegcetacoplan 270 milligrams (mg)/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Period Title: Overall Study
Started 4
Completed [1] 4
Not Completed 0
[1]
All subjects transitioned to an open-label extension study after Day 364.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Baseline Participants 4
Hide Baseline Analysis Population Description
The safety set consisted of all subjects who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants
30.8  (11.81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
Female
3
  75.0%
Male
1
  25.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 4 participants
White
4
 100.0%
Not Hispanic or Latino
4
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 4 participants
Bulgaria 2
Serbia 2
1.Primary Outcome
Title Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity
Hide Description TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possible, probable, or definite. TEAEs were graded according to the Common Terminology Criteria for Adverse Events (v4.03) based on: Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening, Grade 5: Death related to AE.
Time Frame From Day 1 to 30 days after the last dose (approximately 56 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Measure Type: Count of Participants
Unit of Measure: Participants
All TEAEs 3
Treatment-related TEAEs 2
Serious TEAEs 1
TEAEs leading to study drug discontinuation 0
TEAEs with mild intensity 2
TEAEs with moderate intensity 0
TEAEs with severe intensity 1
TEAEs with life threatening intensity 0
TEAEs leading to death 0
2.Primary Outcome
Title Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level
Hide Description Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame Baseline and Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat (ITT) set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: units/liter
-2322.8  (635.41)
3.Primary Outcome
Title Mean Change From Baseline in Haptoglobin Level
Hide Description Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame Baseline and Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: grams/liter
0.08  (0.150)
4.Primary Outcome
Title Mean Change From Baseline in Hemoglobin (Hb) Level
Hide Description Hematology assessments of Hb were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame Baseline and Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: grams/deciliter
5.27  (1.875)
5.Secondary Outcome
Title Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
Hide Description The FACIT-Fatigue scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). With 13 statements the total score had a range of 0 to 52. Higher score corresponds to a higher quality of life (QoL).
Time Frame Baseline and Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: score on a scale
6.5  (5.45)
6.Secondary Outcome
Title Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level
Hide Description Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame Baseline and Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: ARC/nanoliter
-144.3  (98.51)
7.Secondary Outcome
Title Mean Change From Baseline in Total Bilirubin Level
Hide Description Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.
Time Frame Baseline and Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: micromoles/liter
-21.53  (8.358)
8.Secondary Outcome
Title Mean Number of Red Blood Cell (RBC) Transfusions Per Month
Hide Description The number of on-study RBC transfusions was monitored throughout the treatment period.
Time Frame From Day 1 to Day 364
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Full Range)
Unit of Measure: transfusions
0
(0 to 0)
9.Secondary Outcome
Title Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL
Hide Description The LASA consists of 3 items, where the respondents were asked to rate their perceived level of functioning. Specific domains included activity level, ability to carry out daily activities, and an item for overall QoL. Their level of functioning was reported on a 0 to 100 scale with 0 indicates "As low as could be" and 100 indicates "As high as could be". The combined score ranged from 0 to 300, with higher scores corresponding to a higher QoL.
Time Frame Baseline and Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT set consisted of all subjects who received at least 1 dose of study drug.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: score on a scale
66.5  (55.75)
10.Secondary Outcome
Title Mean Serum Concentrations of Pegcetacoplan
Hide Description Serum concentrations of pegcetacoplan at Day 365 are presented.
Time Frame Day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) set consisted of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (ug/mL)
622.0  (92.13)
11.Secondary Outcome
Title Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal)
Hide Description The AUCtotal of pegcetacoplan was estimated using a non-compartmental approach.
Time Frame Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set consisted of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: hour*ug/mL
5818803.2534  (975444.77662)
12.Secondary Outcome
Title Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total)
Hide Description The Ctrough,max,total of pegcetacoplan was estimated using a non-compartmental approach.
Time Frame Blood samples were collected predose and at least 2.5 hours post dose on Day 1 and predose on Days 2 up to Day 365.
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set consisted of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description:
Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: ug/mL
783.5  (116.25)
Time Frame TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks).
Adverse Event Reporting Description The safety set consisted of all subjects who received at least 1 dose of study drug.
 
Arm/Group Title Pegcetacoplan 270 mg/Day
Hide Arm/Group Description Subjects received SC infusions of pegcetacoplan 270 mg/day up to Day 364. Intrasubject dose escalation up to a dosage of 360 mg/day was permitted if clinically indicated.
All-Cause Mortality
Pegcetacoplan 270 mg/Day
Affected / at Risk (%)
Total   0/4 (0.00%)    
Hide Serious Adverse Events
Pegcetacoplan 270 mg/Day
Affected / at Risk (%) # Events
Total   1/4 (25.00%)    
Injury, poisoning and procedural complications   
Rib fracture † 1  1/4 (25.00%)  1
1
Term from vocabulary, MedDRA (21.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Pegcetacoplan 270 mg/Day
Affected / at Risk (%) # Events
Total   3/4 (75.00%)    
General disorders   
Administration site swelling † 1  1/4 (25.00%)  1
Injection site discolouration † 1  1/4 (25.00%)  1
Injection site erythema † 1  1/4 (25.00%)  8
Injection site pruritus † 1  1/4 (25.00%)  1
Injection site swelling † 1  1/4 (25.00%)  4
Infections and infestations   
Rhinitis † 1  1/4 (25.00%)  2
Nervous system disorders   
Dizziness † 1  2/4 (50.00%)  3
Reproductive system and breast disorders   
Scrotal irritation † 1  1/4 (25.00%)  1
Respiratory, thoracic and mediastinal disorders   
Cough † 1  1/4 (25.00%)  1
Skin and subcutaneous tissue disorders   
Erythema † 1  2/4 (50.00%)  37
1
Term from vocabulary, MedDRA (21.0)
†
Indicates events were collected by systematic assessment
Given the small sample size, no conclusions should be drawn from the results summarized and reported as descriptive statistics in Outcome Measures 9-12.
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03593200    
Other Study ID Numbers: APL2-202
First Submitted: June 28, 2018
First Posted: July 20, 2018
Results First Submitted: August 4, 2020
Results First Posted: December 22, 2020
Last Update Posted: December 22, 2020