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Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Pegcetacoplan
Soliris
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:

  • At least 18 years of age
  • Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
  • On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
  • Hb <10.5 g/dL at the Screening Visit
  • Absolute reticulocyte count > 1.0x ULN at the Screening Visit
  • Platelet count of >50,000/mm3 at the Screening Visit
  • Absolute neutrophil count >500/mm3 at the Screening Visit
  • Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
  • Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the Screening and Day -28 Visit (Run-in Period) and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug
  • Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug
  • Willing and able to give informed consent
  • Willing and able to self-administer APL-2 (administration by caregiver will be allowed)
  • Have a body mass index (BMI) ≤35.0 kg/m2

Exclusion Criteria:

  • Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2)
  • Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
  • Hereditary complement deficiency
  • History of bone marrow transplantation
  • History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
  • Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
  • Currently breast-feeding women
  • Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk of participating in the study or confound the outcome of the study

This study includes cardiac safety evaluations. The following cardiac eligibility criteria are necessary to avoid confounding the cardiac safety outcomes:

  • History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death
  • Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2
  • QTcF > 470 ms, PR > 280 ms
  • Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities
  • Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening
  • Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stable dose for less than 3 weeks prior to dosing
  • Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than one week prior to the first dose of study medication (must have a repeat screening ECG after one week of prophylactic antibiotics with QTcF < 470 ms)

Sites / Locations

  • University of Southern California
  • Sarcoma Oncology Research Center
  • Denver Health
  • Georgetown University Hospital
  • Cancer Specialists of North Florida
  • Lakes Research
  • Mid Florida Hematology and Oncology
  • Winship Cancer Institute of Emory University
  • Northwestern University
  • Investigative Clinical Research of Indiana
  • Cancer & Hematology Centers of Western Michigan
  • New York Cancer & Blood Specialists
  • Roswell Park Cancer Institute
  • New York Cancer & Blood Specialists
  • Duke University Medical Center
  • Good Samaritan Hospital
  • University of Tennessee Medical Center
  • Baptist Cancer Center
  • HOPE Cancer Center of East Texas
  • Royal Melbourne Hospital
  • Cliniques Universitaires Saint-Luc
  • AZ Delta Campus Wilgenstraat
  • University of Alberta
  • Toronto General Hospital
  • Centre Hospitalier Annecy Genevois
  • Centre Hospitalier William Morey
  • Centre Hospitalier Universitaire de Lille
  • Institut Paoli-Calmettes Marseille
  • Hôpital Saint-Louis
  • Centre Hospitalier Lyon Sud
  • Centre Hospitalier de Saint-Quentin
  • Institut Universitaire du Cancer Toulouse - Oncopole
  • Universitätsklinikum Ulm
  • Uniklinik RWTH Aachen
  • Universitätsklinikum Essen
  • Universitätsklinikum Hamburg Eppendorf
  • Japanese Red Cross Nagoya Daiichi Hospital
  • Japanese Red Cross Nagoya Daini Hospital
  • University of Tsukuba Hospital
  • Shinshu University Hospital
  • Okayama University Hospital
  • Juntendo University Hospital
  • NTT Medical Center Tokyo
  • Kinan Hospital
  • Soonchunhyang University Bucheon Hospital
  • Chungnam National University Hospital
  • Samsung Medical Center
  • Pavlov First Saint Petersburg State Medical University of Russian Ministry of Health
  • Pavlov First Saint Petersburg State Medical University
  • Institution of Health Care of Tyumen Region
  • Hospital Universitario de Gran Canaria Dr. Negrín
  • Hospital Universitario Politécnico La Fe
  • St. James' Institute of Oncology, Leeds Teaching Hospitals

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pegcetacoplan

Eculizumab

Arm Description

1080 mg pegcetacoplan administered subcutaneously twice-weekly or every three days.

Complement (C5) Inhibitor.

Outcomes

Primary Outcome Measures

Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.

Secondary Outcome Measures

Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP
Subjects who experienced more than 1 transfusion during the RCP are only counted once. Subjects who did not have a transfusion but withdrew before Week 16 were considered as having a transfusion in the analysis of transfusion avoidance.
LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP
The FACIT-fatigue scale version 4 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. A higher score corresponds to a higher quality of life (QoL). Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.
Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16
Hb response was defined as an increase of at least 1 g/dL in Hb from Baseline at Week 16. Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16
Reticulocyte normalization was defined as the ARC being below the upper limit of the gender-specific normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 were classified as nonresponders.
Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16
Hb normalization was defined as the Hb level being above the lower limit of the normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 are classified as nonnormalization.
LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP
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.
LS Mean Change From Baseline to Week 16 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Scale (QLQ-C30) Scores During the RCP
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are 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'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Total Number of PRBC Units Transfused During the RCP
Subjects who withdrew during the RCP before Week 16 will have their number of units of PRBC estimated from the duration they were in the study.
Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Mean Change From Baseline to Week 48 in ARC During the Treatment Period
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Mean Change From Week 17 to Week 48 in ARC During the Open-label Period
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period
The FACIT-fatigue scale version 4 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. A higher score corresponds to a higher QoL. Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.
Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period
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 QoL.
Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period
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.
Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period
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 QoL.
Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are 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'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are 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'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Total Number of PRBC Units Transfused During the Open-Label Period
Number of units of PRBC transfused to subjects in the open-label period are reported.

Full Information

First Posted
April 10, 2018
Last Updated
March 1, 2022
Sponsor
Apellis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03500549
Brief Title
Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official Title
A Phase III, Randomized, Multi-Center, Open-Label, Active-Comparator Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
June 14, 2018 (Actual)
Primary Completion Date
November 14, 2019 (Actual)
Study Completion Date
August 13, 2020 (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 APL-2 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
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pegcetacoplan
Arm Type
Experimental
Arm Description
1080 mg pegcetacoplan administered subcutaneously twice-weekly or every three days.
Arm Title
Eculizumab
Arm Type
Active Comparator
Arm Description
Complement (C5) Inhibitor.
Intervention Type
Drug
Intervention Name(s)
Pegcetacoplan
Other Intervention Name(s)
APL-2
Intervention Description
Complement (C3) Inhibitor
Intervention Type
Drug
Intervention Name(s)
Soliris
Intervention Description
Complement (C5) Inhibitor
Primary Outcome Measure Information:
Title
Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP
Description
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 16
Secondary Outcome Measure Information:
Title
Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP
Description
Subjects who experienced more than 1 transfusion during the RCP are only counted once. Subjects who did not have a transfusion but withdrew before Week 16 were considered as having a transfusion in the analysis of transfusion avoidance.
Time Frame
Day 1 to Week 16
Title
LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP
Description
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 16
Title
LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP
Description
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 16
Title
LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP
Description
The FACIT-fatigue scale version 4 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. A higher score corresponds to a higher quality of life (QoL). Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.
Time Frame
Baseline and Week 16
Title
Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16
Description
Hb response was defined as an increase of at least 1 g/dL in Hb from Baseline at Week 16. Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 16
Title
Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16
Description
Reticulocyte normalization was defined as the ARC being below the upper limit of the gender-specific normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 were classified as nonresponders.
Time Frame
Week 16
Title
Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16
Description
Hb normalization was defined as the Hb level being above the lower limit of the normal range at Week 16, censored for transfusions. Subjects who received a transfusion between Day 1 and Week 16 or withdrew without providing efficacy data at Week 16 are classified as nonnormalization.
Time Frame
Week 16
Title
LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP
Description
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 16
Title
LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP
Description
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 16
Title
LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP
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 Week 16
Title
LS Mean Change From Baseline to Week 16 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Scale (QLQ-C30) Scores During the RCP
Description
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are 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'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Time Frame
Baseline and Week 16
Title
Total Number of PRBC Units Transfused During the RCP
Description
Subjects who withdrew during the RCP before Week 16 will have their number of units of PRBC estimated from the duration they were in the study.
Time Frame
Day 1 to Week 16
Title
Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period
Description
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 48
Title
Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period
Description
Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Week 17 and Week 48
Title
Mean Change From Baseline to Week 48 in ARC During the Treatment Period
Description
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 48
Title
Mean Change From Week 17 to Week 48 in ARC During the Open-label Period
Description
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Week 17 and Week 48
Title
Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period
Description
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Baseline and Week 48
Title
Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period
Description
Baseline was the average of available measurements recorded from central laboratory before taking the first dose of pegcetacoplan. Analysis excluded data before the RCP and was censored for transfusions.
Time Frame
Week 17 and Week 48
Title
Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period
Description
The FACIT-fatigue scale version 4 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. A higher score corresponds to a higher QoL. Baseline was the last available, nonmissing observation before taking the first dose of pegcetacoplan. Data collected after transfusion is excluded from analysis.
Time Frame
Baseline and Week 48
Title
Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period
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 QoL.
Time Frame
Week 17 and Week 48
Title
Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period
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 Week 48
Title
Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period
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 QoL.
Time Frame
Week 17 and Week 48
Title
Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period
Description
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are 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'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Time Frame
Baseline and Week 48
Title
Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period
Description
The EORTC QLQ-C30 questionnaire (version 3.0) consists of 30 questions comprised of both multi-item scales and single-item measures to assess overall QoL in subjects. Questions are 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'). The raw scale scores were linear transformed, producing scale scores that ranged from 0% to 100%. A high scale score represents a higher response level. Hence for the functional scales and the global health status a higher score indicates a better QoL, whilst for the symptom scale scores this is implied by a lower score.
Time Frame
Week 17 and Week 48
Title
Total Number of PRBC Units Transfused During the Open-Label Period
Description
Number of units of PRBC transfused to subjects in the open-label period are reported.
Time Frame
Week 17 to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: At least 18 years of age Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit Hb <10.5 g/dL at the Screening Visit Absolute reticulocyte count > 1.0x ULN at the Screening Visit Platelet count of >50,000/mm3 at the Screening Visit Absolute neutrophil count >500/mm3 at the Screening Visit Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the Screening and Day -28 Visit (Run-in Period) and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug Willing and able to give informed consent Willing and able to self-administer APL-2 (administration by caregiver will be allowed) Have a body mass index (BMI) ≤35.0 kg/m2 Exclusion Criteria: Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2) Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening Hereditary complement deficiency History of bone marrow transplantation History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer) Currently breast-feeding women Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk of participating in the study or confound the outcome of the study This study includes cardiac safety evaluations. The following cardiac eligibility criteria are necessary to avoid confounding the cardiac safety outcomes: History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2 QTcF > 470 ms, PR > 280 ms Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stable dose for less than 3 weeks prior to dosing Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than one week prior to the first dose of study medication (must have a repeat screening ECG after one week of prophylactic antibiotics with QTcF < 470 ms)
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Sarcoma Oncology Research Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90403
Country
United States
Facility Name
Denver Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
Cancer Specialists of North Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
Lakes Research
City
Miami Lakes
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Mid Florida Hematology and Oncology
City
Orange City
State/Province
Florida
ZIP/Postal Code
32763
Country
United States
Facility Name
Winship Cancer Institute of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Investigative Clinical Research of Indiana
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Cancer & Hematology Centers of Western Michigan
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
New York Cancer & Blood Specialists
City
Bronx
State/Province
New York
ZIP/Postal Code
10469
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
New York Cancer & Blood Specialists
City
East Setauket
State/Province
New York
ZIP/Postal Code
11733
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Good Samaritan Hospital
City
Corvallis
State/Province
Oregon
ZIP/Postal Code
97330
Country
United States
Facility Name
University of Tennessee Medical Center
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Baptist Cancer Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
HOPE Cancer Center of East Texas
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Cliniques Universitaires Saint-Luc
City
Woluwe-Saint-Lambert
State/Province
Vlaams-Brabant
ZIP/Postal Code
1200
Country
Belgium
Facility Name
AZ Delta Campus Wilgenstraat
City
Roeselare
State/Province
West-Vlaanderen
ZIP/Postal Code
8800
Country
Belgium
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G3
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M9A1G2
Country
Canada
Facility Name
Centre Hospitalier Annecy Genevois
City
Annecy
ZIP/Postal Code
74374
Country
France
Facility Name
Centre Hospitalier William Morey
City
Chalon-sur-Saône
ZIP/Postal Code
71100
Country
France
Facility Name
Centre Hospitalier Universitaire de Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Institut Paoli-Calmettes Marseille
City
Marseille
ZIP/Postal Code
13009
Country
France
Facility Name
Hôpital Saint-Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Facility Name
Centre Hospitalier de Saint-Quentin
City
Saint-Quentin
ZIP/Postal Code
02321
Country
France
Facility Name
Institut Universitaire du Cancer Toulouse - Oncopole
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Universitätsklinikum Ulm
City
Ulm
State/Province
Baden-Württemberg
ZIP/Postal Code
89081
Country
Germany
Facility Name
Uniklinik RWTH Aachen
City
Aachen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
52074
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitätsklinikum Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Japanese Red Cross Nagoya Daiichi Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
453-8511
Country
Japan
Facility Name
Japanese Red Cross Nagoya Daini Hospital
City
Showa-ku
State/Province
Aichi
ZIP/Postal Code
453-8650
Country
Japan
Facility Name
University of Tsukuba Hospital
City
Tsukuba
State/Province
Ibaraki
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Shinshu University Hospital
City
Matsumoto
State/Province
Nagano
ZIP/Postal Code
390-8621
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama-shi
State/Province
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
Juntendo University Hospital
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8421
Country
Japan
Facility Name
NTT Medical Center Tokyo
City
Shinagawa-ku
State/Province
Tokyo
ZIP/Postal Code
141-8625
Country
Japan
Facility Name
Kinan Hospital
City
Tanabe
State/Province
Wakayama
ZIP/Postal Code
646-8588
Country
Japan
Facility Name
Soonchunhyang University Bucheon Hospital
City
Bucheon
ZIP/Postal Code
14584
Country
Korea, Republic of
Facility Name
Chungnam National University Hospital
City
Daejeon
ZIP/Postal Code
35015
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Pavlov First Saint Petersburg State Medical University of Russian Ministry of Health
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Pavlov First Saint Petersburg State Medical University
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Institution of Health Care of Tyumen Region
City
Tyumen
ZIP/Postal Code
625023
Country
Russian Federation
Facility Name
Hospital Universitario de Gran Canaria Dr. Negrín
City
Las Palmas De Gran Canaria
ZIP/Postal Code
35010
Country
Spain
Facility Name
Hospital Universitario Politécnico La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
St. James' Institute of Oncology, Leeds Teaching Hospitals
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
36055332
Citation
de Latour RP, Szer J, Weitz IC, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro CM, Nishimori H, Ajayi T, Al-Adhami M, Deschatelets P, Francois C, Grossi F, Risitano AM, Hillmen P. Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial. Lancet Haematol. 2022 Sep;9(9):e648-e659. doi: 10.1016/S2352-3026(22)00210-1.
Results Reference
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PubMed Identifier
35869984
Citation
Cella D, Sarda SP, Hsieh R, Fishman J, Hakimi Z, Hoffman K, Al-Adhami M, Nazir J, Cutts K, Lenderking WR. Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study. Ann Hematol. 2022 Sep;101(9):1905-1914. doi: 10.1007/s00277-022-04887-8. Epub 2022 Jul 23.
Results Reference
derived
PubMed Identifier
35796199
Citation
Hakimi Z, Wilson K, McAughey E, Pochopien M, Wojciechowski P, Toumi M, Knight C, Sarda SP, Patel N, Wiseman C, de Castro NP, Nazir J, Kelly RJ. The cost-effectiveness, of pegcetacoplan compared with ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria, in a UK setting. J Comp Eff Res. 2022 Sep;11(13):969-985. doi: 10.2217/cer-2022-0076. Epub 2022 Jul 7.
Results Reference
derived
PubMed Identifier
34445916
Citation
Bhak RH, Mody-Patel N, Baver SB, Kunzweiler C, Yee CW, Sundaresan S, Swartz N, Duh MS, Krishnan S, Sarda SP. Comparative effectiveness of pegcetacoplan versus ravulizumab in patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a matching-adjusted indirect comparison. Curr Med Res Opin. 2021 Nov;37(11):1913-1923. doi: 10.1080/03007995.2021.1971182. Epub 2021 Sep 3.
Results Reference
derived
PubMed Identifier
33730455
Citation
Hillmen P, Szer J, Weitz I, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, Peffault de la Tour R. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021 Mar 18;384(11):1028-1037. doi: 10.1056/NEJMoa2029073.
Results Reference
derived

Learn more about this trial

Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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