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A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With PNH

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
APL-2
Sponsored by
Apellis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Be at least 18 years old (inclusive).
  • Have LDH ≥1.5 x ULN at the screening visit.
  • Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or monocyte clone >10%).
  • Have Hb less than the lower limit of normal (LLN) at the screening visit.
  • Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less than/equal to ULN at the screening visit, based on central laboratory reference ranges. If a subject is receiving iron supplements at screening, the Investigator must ensure that the subject's dose has been stable for 4 weeks prior to screening, and it must be maintained throughout the study. Subjects not receiving iron at screening must not start iron supplementation during the course of the study.
  • Body mass index (BMI) ≤ 35 kg/m2 at the screening visit.
  • Have a platelet count of >50,000/mm3 at the screening visit.
  • Have an absolute neutrophil count >500/mm3 at the screening visit.

Exclusion Criteria:

  • Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to screening.
  • Hereditary complement deficiency.
  • History of bone marrow transplantation.

  • Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time period indicated below prior to screening:

    • Erythropoietin or immunosuppressants for at least 8 weeks
    • Systemic corticosteroids for at least 4 weeks
    • Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least 4 weeks
    • Iron supplements, vitamin B12, or folic acid for at least 4 weeks
    • Low-molecular-weight heparin for at least 4 weeks

Sites / Locations

  • Julian Coronel Medical Center
  • Research Center of the Colombian Clinical Life Cancer Foundation
  • Queen Mary Hospital
  • Princess Margaret Hospital
  • Prince and Wales Hospital
  • Hospital Ampang
  • University Malaya Medical Centre
  • Hospital Universitario Dr.Jose Eleuterio Gonzalez
  • Hospital Cayetano Heredia
  • Hospital Cayetano Heredia
  • Hospital Nacional Dos de Mayo
  • Baguio General Hospital
  • Perpetual Succour Hospital
  • Mary Mediatrix Medical Center
  • Makati Medical Centre
  • The Medical City
  • St. Lukes Medical Centre
  • Independent Public Clinical Hospital
  • Institute of Hematology and Transfusiology
  • EMC Medical Institute
  • Clinical Centre of Serbia
  • Singapore General Hospital (SGH)
  • Ramathibodi Hospital
  • Siriraj Hospital
  • Hospital for Tropical disease
  • Phramongkutklao Hospital
  • Maharaj Nakorn Chiang Mai Hospital
  • Srinagaring Hospital
  • Thammasat University Hospital
  • Songklanagaring Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Standard of Care (SOC) excluding complement inhibitors

1,080mg APL-2 administered subcutaneously twice weekly

Arm Description

Outcomes

Primary Outcome Measures

Number of Subjects Who Achieved Hemoglobin (Hb) Stabilization
The Hb stabilization was defined as avoidance of a >1 gram per deciliter (g/dL) decrease in Hb concentration from Baseline in the absence of transfusion through Week 26.
Change From Baseline in Lactate Dehydrogenase (LDH) Concentration At Week 26
The LDH concentration was analyzed using an analysis of covariance (ANCOVA) model with a last observation carried forward (LOCF) and a baseline observation carried forward (BOCF) approach for handling missing data. Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.

Secondary Outcome Measures

Number of Subjects With an Hb Response in the Absence of Transfusions
An Hb response was defined as a =>1 g/dL increase in Hb from baseline at Week 26.
Change From Baseline in Absolute Reticulocyte Count (ARC) at Week 26
Blood samples were collected via direct venipuncture at the specific time points to determine ARC. Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Change From Baseline in Hb Concentration at Week 26
Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Percentage of Subjects Who Received Transfusion or Decrease of Hb >2 g/dL From Baseline
Transfusion refers to any transfusion of PRBC, leukocyte-depleted red blood cells (LDPRC), leukocyte poor packed red blood cell (LPRC), leukocyte poor blood (LPB) or whole blood.
Percentage of Subjects With Transfusion Avoidance
Transfusion avoidance was defined as the percentage of subjects who did not require a transfusion during the RCP. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.
Number of PRBC Units Transfused From Baseline Through Week 26
The number of units of PRBC transfusions was estimated. In one transfusion subjects received one or more units.
Change From Baseline in Functional Assessment of Chronic Illness Therapy- (FACIT-Fatigue) Scale Score at Week 26
The FACIT-Fatigue Scale is a 13-item Likert scaled instrument that is self-administered by the subjects during clinic visits. Subjects were presented with 13 statements and asked to indicate their responses as it applied to the past 7 days. The 5 possible responses are "Not at all" (0), "A little bit" (1), "Somewhat" (2), "Quite a bit" (3), and "Very much" (4). With 13 statements, the total score has a range of 0 to 52. The higher score corresponded to a higher quality of life. Baseline is defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Percentage of Subjects With Hb Normalization Levels at Week 26
Normalization of Hb levels defined as >= 1x LLN at Week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.
Percentage of Subjects With LDH Normalization at Week 26
The LDH normalization was defined as LDH <= 1xupper limit of normal (ULN) of normal range at week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPPRC, LPRC, LPB or whole blood.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30) Scores at Week 26
The EORTC QLQ-C30 questionnaire (version 3.0) consisted of 30 questions comprised of both multi-item scales and single-item measures to assess overall quality of life in subjects. Questions were designated by functional scales, symptom scales, and global subject QOL/overall perceived health status. For the first 28 questions the 4 possible responses are "Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). Each scale has a range of 0% - 100%. A high scale score represents a higher response level. Baseline is defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Change From Baseline in Linear Analog Assessment (LASA) Scales Score at Week 26
The LASA consisted of 3 items asking respondents to rate their perceived level of functioning. Specific domains include activity level, ability to carry out daily activities, and an item for overall QOL. Their level of functioning was reported on a 0-100 scale with 0 representing "As low as could be" and 100 representing "As high as could be".
Percentage of Subjects With ARC Normalization
Absolute reticulocyte count normalization is defined as ARC < 1x ULN of the gender-specific normal range at week 26 in the absence of transfusion. Subjects who received a transfusion or withdraw from study or escaped from SoC to pegcetacoplan treatment group or lost to follow up without providing efficacy data at Week 26 were classified as non-responders. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.
Number of Subjects With Failure of Hb Stabilization
Hb stabilization is defined as avoidance of a >1 g/dL decrease in Hb levels from baseline through Week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.
Time to First PRBC Transfusion
Time to first-on-study PRBC transfusions during RCP were reported. Here NA indicates not estimable.

Full Information

First Posted
September 9, 2019
Last Updated
October 14, 2022
Sponsor
Apellis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04085601
Brief Title
A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With PNH
Official Title
A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
August 27, 2019 (Actual)
Primary Completion Date
June 23, 2021 (Actual)
Study Completion Date
June 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apellis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Evaluation of the Efficacy and Safety of Pegcetacoplan in Patients with Paroxysmal Nocturnal Hemoglobinuria .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care (SOC) excluding complement inhibitors
Arm Type
No Intervention
Arm Title
1,080mg APL-2 administered subcutaneously twice weekly
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
APL-2
Intervention Description
Complement (C3) Inhibitor
Primary Outcome Measure Information:
Title
Number of Subjects Who Achieved Hemoglobin (Hb) Stabilization
Description
The Hb stabilization was defined as avoidance of a >1 gram per deciliter (g/dL) decrease in Hb concentration from Baseline in the absence of transfusion through Week 26.
Time Frame
From Baseline (Day 1) up to Week 26
Title
Change From Baseline in Lactate Dehydrogenase (LDH) Concentration At Week 26
Description
The LDH concentration was analyzed using an analysis of covariance (ANCOVA) model with a last observation carried forward (LOCF) and a baseline observation carried forward (BOCF) approach for handling missing data. Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Time Frame
Baseline (Day 1) and Week 26
Secondary Outcome Measure Information:
Title
Number of Subjects With an Hb Response in the Absence of Transfusions
Description
An Hb response was defined as a =>1 g/dL increase in Hb from baseline at Week 26.
Time Frame
Baseline and Week 26
Title
Change From Baseline in Absolute Reticulocyte Count (ARC) at Week 26
Description
Blood samples were collected via direct venipuncture at the specific time points to determine ARC. Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Time Frame
Baseline and Week 26
Title
Change From Baseline in Hb Concentration at Week 26
Description
Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Time Frame
Baseline and Week 26
Title
Percentage of Subjects Who Received Transfusion or Decrease of Hb >2 g/dL From Baseline
Description
Transfusion refers to any transfusion of PRBC, leukocyte-depleted red blood cells (LDPRC), leukocyte poor packed red blood cell (LPRC), leukocyte poor blood (LPB) or whole blood.
Time Frame
At Week 26
Title
Percentage of Subjects With Transfusion Avoidance
Description
Transfusion avoidance was defined as the percentage of subjects who did not require a transfusion during the RCP. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.
Time Frame
At Week 26
Title
Number of PRBC Units Transfused From Baseline Through Week 26
Description
The number of units of PRBC transfusions was estimated. In one transfusion subjects received one or more units.
Time Frame
Up to Week 26
Title
Change From Baseline in Functional Assessment of Chronic Illness Therapy- (FACIT-Fatigue) Scale Score at Week 26
Description
The FACIT-Fatigue Scale is a 13-item Likert scaled instrument that is self-administered by the subjects during clinic visits. Subjects were presented with 13 statements and asked to indicate their responses as it applied to the past 7 days. The 5 possible responses are "Not at all" (0), "A little bit" (1), "Somewhat" (2), "Quite a bit" (3), and "Very much" (4). With 13 statements, the total score has a range of 0 to 52. The higher score corresponded to a higher quality of life. Baseline is defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Time Frame
Baseline and Week 26
Title
Percentage of Subjects With Hb Normalization Levels at Week 26
Description
Normalization of Hb levels defined as >= 1x LLN at Week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.
Time Frame
Baseline and Week 26
Title
Percentage of Subjects With LDH Normalization at Week 26
Description
The LDH normalization was defined as LDH <= 1xupper limit of normal (ULN) of normal range at week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPPRC, LPRC, LPB or whole blood.
Time Frame
At Week 26
Title
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30) Scores at Week 26
Description
The EORTC QLQ-C30 questionnaire (version 3.0) consisted of 30 questions comprised of both multi-item scales and single-item measures to assess overall quality of life in subjects. Questions were designated by functional scales, symptom scales, and global subject QOL/overall perceived health status. For the first 28 questions the 4 possible responses are "Not at all' (1), 'A little' (2), 'Quite a bit' (3) and 'Very much' (4). For the remaining 2 questions the response is requested on a 7-point scale from 1 ('Very poor') to 7 ('Excellent'). Each scale has a range of 0% - 100%. A high scale score represents a higher response level. Baseline is defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.
Time Frame
Baseline and Week 26
Title
Change From Baseline in Linear Analog Assessment (LASA) Scales Score at Week 26
Description
The LASA consisted of 3 items asking respondents to rate their perceived level of functioning. Specific domains include activity level, ability to carry out daily activities, and an item for overall QOL. Their level of functioning was reported on a 0-100 scale with 0 representing "As low as could be" and 100 representing "As high as could be".
Time Frame
Baseline and Week 26
Title
Percentage of Subjects With ARC Normalization
Description
Absolute reticulocyte count normalization is defined as ARC < 1x ULN of the gender-specific normal range at week 26 in the absence of transfusion. Subjects who received a transfusion or withdraw from study or escaped from SoC to pegcetacoplan treatment group or lost to follow up without providing efficacy data at Week 26 were classified as non-responders. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.
Time Frame
At Week 26
Title
Number of Subjects With Failure of Hb Stabilization
Description
Hb stabilization is defined as avoidance of a >1 g/dL decrease in Hb levels from baseline through Week 26 in the absence of transfusion. Transfusion refers to any transfusion of PRBC, LDPRC, LPRC, LPB or whole blood.
Time Frame
Up to Week 26
Title
Time to First PRBC Transfusion
Description
Time to first-on-study PRBC transfusions during RCP were reported. Here NA indicates not estimable.
Time Frame
Up to Week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Be at least 18 years old (inclusive). Have LDH ≥1.5 x ULN at the screening visit. Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or monocyte clone >10%). Have Hb less than the lower limit of normal (LLN) at the screening visit. Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less than/equal to ULN at the screening visit, based on central laboratory reference ranges. If a subject is receiving iron supplements at screening, the Investigator must ensure that the subject's dose has been stable for 4 weeks prior to screening, and it must be maintained throughout the study. Subjects not receiving iron at screening must not start iron supplementation during the course of the study. Body mass index (BMI) ≤ 35 kg/m2 at the screening visit. Have a platelet count of >50,000/mm3 at the screening visit. Have an absolute neutrophil count >500/mm3 at the screening visit. Exclusion Criteria: Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to screening. Hereditary complement deficiency. History of bone marrow transplantation. Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time period indicated below prior to screening: Erythropoietin or immunosuppressants for at least 8 weeks Systemic corticosteroids for at least 4 weeks Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least 4 weeks Iron supplements, vitamin B12, or folic acid for at least 4 weeks Low-molecular-weight heparin for at least 4 weeks
Facility Information:
Facility Name
Julian Coronel Medical Center
City
Cali
Country
Colombia
Facility Name
Research Center of the Colombian Clinical Life Cancer Foundation
City
Medellín
Country
Colombia
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Princess Margaret Hospital
City
Kwai Chung
Country
Hong Kong
Facility Name
Prince and Wales Hospital
City
Sha Tin
Country
Hong Kong
Facility Name
Hospital Ampang
City
Ampang
State/Province
Selangor
ZIP/Postal Code
68000
Country
Malaysia
Facility Name
University Malaya Medical Centre
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Hospital Universitario Dr.Jose Eleuterio Gonzalez
City
Monterrey
Country
Mexico
Facility Name
Hospital Cayetano Heredia
City
Jesús María
State/Province
Lima
ZIP/Postal Code
15072
Country
Peru
Facility Name
Hospital Cayetano Heredia
City
San Martin de Porres
State/Province
Lima
ZIP/Postal Code
15102
Country
Peru
Facility Name
Hospital Nacional Dos de Mayo
City
Lima
ZIP/Postal Code
15003
Country
Peru
Facility Name
Baguio General Hospital
City
Benguet
ZIP/Postal Code
2600
Country
Philippines
Facility Name
Perpetual Succour Hospital
City
Cebu City
ZIP/Postal Code
6000
Country
Philippines
Facility Name
Mary Mediatrix Medical Center
City
Lipa City
ZIP/Postal Code
4217
Country
Philippines
Facility Name
Makati Medical Centre
City
Makati City
ZIP/Postal Code
1229
Country
Philippines
Facility Name
The Medical City
City
Pasig City
ZIP/Postal Code
1604
Country
Philippines
Facility Name
St. Lukes Medical Centre
City
Quezon City
ZIP/Postal Code
1112
Country
Philippines
Facility Name
Independent Public Clinical Hospital
City
Lubin
ZIP/Postal Code
20-081
Country
Poland
Facility Name
Institute of Hematology and Transfusiology
City
Warsaw
ZIP/Postal Code
02-776
Country
Poland
Facility Name
EMC Medical Institute
City
Wrocław
ZIP/Postal Code
50-220
Country
Poland
Facility Name
Clinical Centre of Serbia
City
Belgrade
Country
Serbia
Facility Name
Singapore General Hospital (SGH)
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Ramathibodi Hospital
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Siriraj Hospital
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Hospital for Tropical disease
City
Bangkok
Country
Thailand
Facility Name
Phramongkutklao Hospital
City
Bangkok
Country
Thailand
Facility Name
Maharaj Nakorn Chiang Mai Hospital
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Srinagaring Hospital
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Thammasat University Hospital
City
Pathum Thani
ZIP/Postal Code
12120
Country
Thailand
Facility Name
Songklanagaring Hospital
City
Songkhla
ZIP/Postal Code
90110
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
34922648
Citation
Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.
Results Reference
derived

Learn more about this trial

A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With PNH

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