Clinical Trial Results:
A Phase 2a, Open-Label, Multiple Dose Study to Assess the Safety, Efficacy, and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects with Paroxysmal Nocturnal Hemoglobinuria (PNH)
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Summary
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EudraCT number |
2017-005140-16 |
Trial protocol |
BG GR |
Global end of trial date |
22 Oct 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Oct 2020
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First version publication date |
22 Oct 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
APL2-202
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03593200 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Apellis Pharmaceuticals, Inc
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Sponsor organisation address |
100 5th Avenue, Waltham, Massachusetts, United States, 02451
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Public contact |
Apellis Clinical Trial Information Line, Apellis Pharmaceuticals, Inc, 1 833-284-6361, clinicaltrials@apellis.com
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Scientific contact |
Apellis Clinical Trial Information Line, Apellis Pharmaceuticals, Inc, 1 833-284-6361, clinicaltrials@apellis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Oct 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Oct 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of multiple subcutaneous (SC) doses of pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who had not received treatment with eculizumab (Soliris®) in the past. The proposed dosage of pegcetacoplan was 270 milligrams (mg)/day.
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Protection of trial subjects |
This research was carried out in accordance with the protocol, applicable regulations, the ethical principles set forth in the Declaration of Helsinki, and the International Council for Harmonisation Good Clinical Practice E6 (R2) guideline.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Aug 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Bulgaria: 2
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Country: Number of subjects enrolled |
Serbia: 2
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Worldwide total number of subjects |
4
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
4
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This Phase 2a, open-label, multiple-dose study was conducted in subjects with PNH who had not received treatment with eculizumab (Soliris®) in the past, between 16 August 2018 and 22 October 2019. | ||||||
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Pre-assignment
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Screening 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. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Pegcetacoplan 270 mg/day | ||||||
Arm 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. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Pegcetacoplan
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Investigational medicinal product code |
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Other name |
APL-2
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Pegcetacoplan was administered as a sterile solution up to 40 mg/milliliter (mL) in acetate-buffered mannitol administered by SC infusion. Subjects self-administered the SC infusions after receiving appropriate training by a research nurse or other study personnel.
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Baseline characteristics reporting groups
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Reporting group title |
Pegcetacoplan 270 mg/day
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Reporting 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pegcetacoplan 270 mg/day
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Reporting 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. | ||
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End point title |
Number of subjects with Treatment Emergent Adverse Events (TEAEs) Including by Severity [1] | ||||||||||||||||||||||||
End point 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. Analysis performed on the safety set consisting of all subjects who received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
From Day 1 to 30 days after the last dose (approximately 56 weeks)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were reported for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Mean Change from Baseline in Lactate Dehydrogenase (LDH) Level [2] | ||||||||
End point 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. Analysis performed on the Intent-to-treat (ITT) set consisting of all subjects who received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Baseline and Day 365
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were reported for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change from Baseline in Haptoglobin Level [3] | ||||||||
End point 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. Analysis performed on the ITT set consisting of all subjects who received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Baseline and Day 365
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were reported for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change from Baseline in Hemoglobin (Hb) Level [4] | ||||||||
End point 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. Analysis performed on the ITT set consisting of all subjects who received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Baseline and Day 365
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were reported for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue Score | ||||||||
End point 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). Analysis performed on the ITT set consisting of all subjects who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 365
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change from Baseline in Absolute Reticulocyte Count (ARC) Level | ||||||||
End point 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. Analysis performed on the ITT set consisting of all subjects who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 365
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change from Baseline in Total Bilirubin Level | ||||||||
End point 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. Analysis performed on the ITT set consisting of all subjects who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 365
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Number of Red Blood Cell (RBC) Transfusions per Month | ||||||||
End point description |
The number of on-study RBC transfusions was monitored throughout the treatment period. Analysis performed on the ITT set consisting of all subjects who received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
From Day 1 to Day 364
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change From Baseline in Linear Analog Scale Assessment (LASA) Score for QoL | ||||||||
End point 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. Analysis performed on the ITT set consisting of all subjects who received at least 1 dose of study drug.
Note: 9999999 indicates that a value was not calculated. Although data were collected for this endpoint, due to the small sample size, the individual values were listed and used for graphical presentation per subject over time only and therefore no summary statistics were prepared. Full range LASA change from baseline scores: 0 to 121.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 365
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Serum Concentrations of Pegcetacoplan | ||||||||
End point description |
Serum concentrations of pegcetacoplan at Day 365 are presented. Analysis performed on the PK set consisting of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.
Note: 9999999 indicates that a value was not calculated. Although data were collected for this endpoint, due to the small sample size, the individual values were listed and used for graphical presentation per subject over time only and therefore no summary statistics were prepared. Full range serum concentrations of pegcetacoplan: 512 to 703 microgram per milliliter (µg/mL).
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End point type |
Secondary
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End point timeframe |
Day 365
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| No statistical analyses for this end point | |||||||||
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End point 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) | ||||||||
End point description |
The AUCtotal of pegcetacoplan was estimated using a non-compartmental approach. Analysis performed on the PK set consisting of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.
Note: 9999999 indicates that a value was not calculated. Although data were collected for this endpoint, due to the small sample size, the individual values were listed and used for graphical presentation per subject over time only and therefore no summary statistics were prepared. Full range AUCtotal of pegcetacoplan: 4850000 to 6910000 hour*µg/mL.
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End point type |
Secondary
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End point 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.
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Maximum Observed Predose Serum Concentration During the Study (Ctrough,Max,Total) | ||||||||
End point description |
The Ctrough,max,total of pegcetacoplan was estimated using a non-compartmental approach. Analysis performed on the PK set consisting of all subjects in the safety set who had at least 1 quantifiable PK sample post dose PK measurement.
Note: 9999999 indicates that a value was not calculated. Although data were collected for this endpoint, due to the small sample size, the individual values were listed and used for graphical presentation per subject over time only and therefore no summary statistics were prepared. Full range Ctrough,max,total of pegcetacoplan: 674 to 912 µg/mL.
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End point type |
Secondary
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End point 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.
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
TEAEs were collected from Day 1 up to 30 days after the last dose of study drug (a total of approximately 56 weeks).
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Adverse event reporting additional description |
The safety set consisted of all subjects who received at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
Pegcetacoplan 270 mg/day
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Reporting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
