Trial Outcomes & Findings for A Phase IIa Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered Pegcetacoplan (APL-2) in Subjects With PNH (NCT NCT03593200)

NCT ID: NCT03593200

Last Updated: 2020-12-22

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 4 participants
• Primary outcome timeframe: From Day 1 to 30 days after the last dose (approximately 56 weeks)
• Results posted on: 2020-12-22

Participant Flow

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.

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.

Participant milestones

Measure	Pegcetacoplan 270 mg/Day 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.
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Age, Continuous	30.8 years STANDARD_DEVIATION 11.81 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Race/Ethnicity, Customized White	4 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	4 Participants n=5 Participants
Region of Enrollment Bulgaria	2 participants n=5 Participants
Region of Enrollment Serbia	2 participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 to 30 days after the last dose (approximately 56 weeks)

Population: The safety set consisted of all subjects who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity TEAEs leading to study drug discontinuation	0 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity TEAEs with moderate intensity	0 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity TEAEs with severe intensity	1 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity All TEAEs	3 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity Treatment-related TEAEs	2 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity Serious TEAEs	1 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity TEAEs with mild intensity	2 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity TEAEs with life threatening intensity	0 Participants
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity TEAEs leading to death	0 Participants

PRIMARY outcome

Timeframe: Baseline and Day 365

Population: The Intent-to-treat (ITT) set consisted of all subjects who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level	-2322.8 units/liter Standard Deviation 635.41

PRIMARY outcome

Timeframe: Baseline and Day 365

Population: The ITT set consisted of all subjects who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Change From Baseline in Haptoglobin Level	0.08 grams/liter Standard Deviation 0.150

PRIMARY outcome

Timeframe: Baseline and Day 365

Population: The ITT set consisted of all subjects who received at least 1 dose of study drug.

Hematology assessments of Hb were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Change From Baseline in Hemoglobin (Hb) Level	5.27 grams/deciliter Standard Deviation 1.875

SECONDARY outcome

Timeframe: Baseline and Day 365

Population: The ITT set consisted of all subjects who received at least 1 dose of study drug.

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).

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score	6.5 score on a scale Standard Deviation 5.45

SECONDARY outcome

Timeframe: Baseline and Day 365

Population: The ITT set consisted of all subjects who received at least 1 dose of study drug.

Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the treatment period.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Change From Baseline in Absolute Reticulocyte Count (ARC) Level	-144.3 ARC/nanoliter Standard Deviation 98.51

SECONDARY outcome

Timeframe: Baseline and Day 365

Population: The ITT set consisted of all subjects who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Change From Baseline in Total Bilirubin Level	-21.53 micromoles/liter Standard Deviation 8.358

SECONDARY outcome

Timeframe: From Day 1 to Day 364

Population: The ITT set consisted of all subjects who received at least 1 dose of study drug.

The number of on-study RBC transfusions was monitored throughout the treatment period.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Number of Red Blood Cell (RBC) Transfusions Per Month	0 transfusions Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline and Day 365

Population: The ITT set consisted of all subjects who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL	66.5 score on a scale Standard Deviation 55.75

SECONDARY outcome

Timeframe: Day 365

Population: The Pharmacokinetic (PK) set consisted of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.

Serum concentrations of pegcetacoplan at Day 365 are presented.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Serum Concentrations of Pegcetacoplan	622.0 microgram per milliliter (ug/mL) Standard Deviation 92.13

SECONDARY outcome

Timeframe: 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.

Population: The PK set consisted of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.

The AUCtotal of pegcetacoplan was estimated using a non-compartmental approach.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Area Under the Serum Concentration Versus Time Curve From Time 0 to the Last Measurable Concentration at the End of the Study (AUCtotal)	5818803.2534 hour*ug/mL Standard Deviation 975444.77662

SECONDARY outcome

Timeframe: 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.

Population: The PK set consisted of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.

The Ctrough,max,total of pegcetacoplan was estimated using a non-compartmental approach.

Outcome measures

Measure	Pegcetacoplan 270 mg/Day n=4 Participants 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.
Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total)	783.5 ug/mL Standard Deviation 116.25

Adverse Events

Pegcetacoplan 270 mg/Day

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pegcetacoplan 270 mg/Day n=4 participants at risk 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.
Injury, poisoning and procedural complications Rib fracture	25.0% 1/4 • Number of events 1 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.

Other adverse events

Measure	Pegcetacoplan 270 mg/Day n=4 participants at risk 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.
General disorders Administration site swelling	25.0% 1/4 • Number of events 1 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
General disorders Injection site discolouration	25.0% 1/4 • Number of events 1 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
General disorders Injection site erythema	25.0% 1/4 • Number of events 8 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
General disorders Injection site pruritus	25.0% 1/4 • Number of events 1 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
General disorders Injection site swelling	25.0% 1/4 • Number of events 4 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
Nervous system disorders Dizziness	50.0% 2/4 • Number of events 3 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Erythema	50.0% 2/4 • Number of events 37 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
Infections and infestations Rhinitis	25.0% 1/4 • Number of events 2 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
Reproductive system and breast disorders Scrotal irritation	25.0% 1/4 • Number of events 1 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 1/4 • Number of events 1 • TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks). The safety set consisted of all subjects who received at least 1 dose of study drug.

Additional Information

Apellis Clinical Trial Information Line

Apellis Pharmaceuticals, Inc

Phone: 1-833-284-6361

Email: clinicaltrials@apellis.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place