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

A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: APL-2

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Cali, Colombia
    • Julian Coronel Medical Center
  • Medellín, Colombia
    • Research Center of the Colombian Clinical Life Cancer Foundation
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Kwai Chung, Hong Kong
    • Princess Margaret Hospital
  • Sha Tin, Hong Kong
    • Prince and Wales Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Hospital Ampang
• Mexico
  • Monterrey, Mexico
    • Hospital Universitario Dr.Jose Eleuterio Gonzalez
• Peru
  • Lima, Peru, 15003
    • Hospital Nacional Dos de Mayo
  • Lima
    • Jesús María, Lima, Peru, 15072
      • Hospital Cayetano Heredia
    • San Martin de Porres, Lima, Peru, 15102
      • Hospital Cayetano Heredia
• Philippines
  • Benguet, Philippines, 2600
    • Baguio General Hospital
  • Cebu City, Philippines, 6000
    • Perpetual Succour Hospital
  • Lipa City, Philippines, 4217
    • Mary Mediatrix Medical Center
  • Makati City, Philippines, 1229
    • Makati Medical Centre
  • Pasig City, Philippines, 1604
    • The Medical City
  • Quezon City, Philippines, 1112
    • St. Lukes Medical Centre
• Poland
  • Lubin, Poland, 20-081
    • Independent Public Clinical Hospital
  • Warsaw, Poland, 02-776
    • Institute of Hematology and Transfusiology
  • Wrocław, Poland, 50-220
    • EMC Medical Institute
• Serbia
  • Belgrade, Serbia
    • Clinical Centre of Serbia
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital (SGH)
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand
    • Phramongkutklao Hospital
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Bangkok, Thailand
    • Hospital for Tropical disease
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
  • Khon Kaen, Thailand, 40002
    • Srinagaring Hospital
  • Pathum Thani, Thailand, 12120
    • Thammasat University Hospital
  • Songkhla, Thailand, 90110
    • Songklanagaring Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Standard of Care (SOC) excluding complement inhibitors
EXPERIMENTAL: 1,080mg APL-2 administered subcutaneously twice weekly	Drug: APL-2; Complement (C3) Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Baseline (Day 1) up to 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.	Baseline (Day 1) and Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 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.	Baseline and Week 26
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.	Baseline and Week 26
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.	At Week 26
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.	At Week 26
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.	Up to Week 26
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.	Baseline and Week 26
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.	Baseline and Week 26
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.	At Week 26
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.	Baseline and Week 26
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".	Baseline and Week 26
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.	At Week 26
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.	Up to Week 26
Time to First PRBC Transfusion	Time to first-on-study PRBC transfusions during RCP were reported. Here NA indicates not estimable.	Up to Week 26

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 27, 2019
• Primary Completion (ACTUAL): June 23, 2021
• Study Completion (ACTUAL): June 23, 2021

Study Registration Dates

• First Submitted: September 9, 2019
• First Submitted That Met QC Criteria: September 9, 2019
• First Posted (ACTUAL): September 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 21, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: APL2-308

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No