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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04085601
Recruitment Status : Completed
First Posted : September 11, 2019
Results First Posted : October 21, 2022
Last Update Posted : October 21, 2022
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

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

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria Drug: APL-2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 27, 2019
Actual Primary Completion Date : June 23, 2021
Actual Study Completion Date : June 23, 2021


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




Primary Outcome Measures :
  1. Number of Subjects Who Achieved Hemoglobin (Hb) Stabilization [ Time Frame: From Baseline (Day 1) up to Week 26 ]
    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.

  2. Change From Baseline in Lactate Dehydrogenase (LDH) Concentration At Week 26 [ Time Frame: Baseline (Day 1) and 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 :
  1. Number of Subjects With an Hb Response in the Absence of Transfusions [ Time Frame: Baseline and Week 26 ]
    An Hb response was defined as a =>1 g/dL increase in Hb from baseline at Week 26.

  2. Change From Baseline in Absolute Reticulocyte Count (ARC) at Week 26 [ Time Frame: Baseline and 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.

  3. Change From Baseline in Hb Concentration at Week 26 [ Time Frame: Baseline and 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.

  4. Percentage of Subjects Who Received Transfusion or Decrease of Hb >2 g/dL From Baseline [ Time Frame: At Week 26 ]
    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.

  5. Percentage of Subjects With Transfusion Avoidance [ Time Frame: At Week 26 ]
    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.

  6. Number of PRBC Units Transfused From Baseline Through Week 26 [ Time Frame: Up to Week 26 ]
    The number of units of PRBC transfusions was estimated. In one transfusion subjects received one or more units.

  7. Change From Baseline in Functional Assessment of Chronic Illness Therapy- (FACIT-Fatigue) Scale Score at Week 26 [ Time Frame: Baseline and 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.

  8. Percentage of Subjects With Hb Normalization Levels at Week 26 [ Time Frame: Baseline and 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.

  9. Percentage of Subjects With LDH Normalization at Week 26 [ Time Frame: 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.

  10. 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 [ Time Frame: Baseline and 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.

  11. Change From Baseline in Linear Analog Assessment (LASA) Scales Score at Week 26 [ Time Frame: Baseline and 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".

  12. Percentage of Subjects With ARC Normalization [ Time Frame: At Week 26 ]
    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.

  13. Number of Subjects With Failure of Hb Stabilization [ Time Frame: Up to Week 26 ]
    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.

  14. Time to First PRBC Transfusion [ Time Frame: Up to Week 26 ]
    Time to first-on-study PRBC transfusions during RCP were reported. Here NA indicates not estimable.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04085601


Locations
Show Show 30 study locations
Sponsors and Collaborators
Apellis Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Apellis Pharmaceuticals, Inc.:
Study Protocol  [PDF] August 10, 2020
Statistical Analysis Plan  [PDF] April 27, 2021

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04085601    
Other Study ID Numbers: APL2-308
First Posted: September 11, 2019    Key Record Dates
Results First Posted: October 21, 2022
Last Update Posted: October 21, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases