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Completed

NCT Number: NCT04888507

Pozelimab and Cemdisiran Combination Therapy in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Switch From Eculizumab Therapy

The primary objective of the study is to evaluate the safety and tolerability of pozelimab and cemdisiran combination therapy in participants with PNH who switch from eculizumab therapy

The secondary objectives of the study are:

* To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of CH50 * To evaluate the effect of the combination treatment on the stability of LDH during the transition period from eculizumab monotherapy to combination with pozelimab and cemdisiran * To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements * To evaluate the effect of the combination treatment on hemoglobin levels * To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life (HRQoL) * To assess the concentrations of total pozelimab and eculizumab in serum; and total cemdisiran and C5 protein in plasma * To assess the immunogenicity of pozelimab and cemdisiran * To assess safety after dose intensification * To evaluate the long-term safety and efficacy of the combination treatment in an optional open-label extension period (OLEP)

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Key information

Conditions

Paroxysmal Nocturnal Hemoglobinuria Anemia Anemia, Hemolytic Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinuria, Paroxysmal Myelodysplastic Syndromes

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Regeneron Study Site

Leeds, LS9 7TF, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Diagnosis of paroxysmal nocturnal hemoglobinuria confirmed by a history of high-sensitivity flow cytometry from prior testing
  • Treated with stable (ie, no change in dose or frequency) eculizumab therapy at the labeled dosing regimen or a higher dose and/or more frequently administered than labeled for at least 12 weeks prior to screening visit

Key Exclusion Criteria:

  • History of bone marrow transplantation or receipt of an organ transplant
  • Body weight <40 kg at screening
  • Current plans for modification of the following background concomitant medications, as applicable, during screening and treatment period: erythropoietin, immunosuppressive drugs, corticosteroids, anti-thrombotic agents, anticoagulants, iron supplements, and folic acid as described in the protocol
  • Any use of complement inhibitor therapy other than eculizumab in the 12 weeks prior to the screening visit or planned use during the study
  • Known hypocellular bone marrow based on a history of reduced age-adjusted bone marrow cellularity and/or bone marrow cellularity ≤25%
  • No documented meningococcal vaccination within 5 years prior to screening visit unless it is documented that vaccination has been administered during the screening period and prior to initiation of study treatment
  • Unable to take antibiotics for meningococcal prophylaxis, if required by local standard of care
  • Any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period
  • Documented positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as described in the protocol
  • Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
  • Recent, unstable medical conditions, excluding PNH and PNH-related complications, within the past 3 months prior to screening visit as described in the protocol
  • Anticipated need for major surgery during the study

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply.

Treatment and study plan

Pozelimab

Drug

Intravenous (IV) loading dose (once) followed after 30 minutes by sub-cutaneous (SC) administration

Other names: REGN3918

Cemdisiran

Drug

SC administration

Other names: ALN-CC5

Primary outcomes

  1. OLTP: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: Up to Day 225

Secondary outcomes

  1. OLTP: Percent Change in Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period

    Time frame: Screening (Day 1) through Day 225

  2. OLTP: Percent Change in LDH From Pre-treatment Through Day 29

    Time frame: Screening (Day 1) through Day 29

  3. OLTP: Percentage of Participants Who Were Transfusion-free From Baseline Through Week 32

    Time frame: Baseline through Week 32

  4. OLTP: Percentage of Participants Who Were Transfusion-free From Week 4 Through Week 32

    Time frame: Week 4 through Week 32

  5. OLTP: Rate of Red Blood Cell (RBC) Transfusions From Baseline Through Week 32

    Time frame: Baseline through Week 32

    The rate of units of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.

  6. OLTP: Rate of RBC Transfusions From Week 4 Through Week 32

    Time frame: Week 4 through Week 32

    The rate of units of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.

  7. OLTP: Number of RBC Units Transfused From Baseline Through Week 32

    Time frame: Baseline through Week 32

  8. OLTP: Number of RBC Units Transfused From Week 4 Through Week 32

    Time frame: Week 4 through Week 32

  9. OLTP: Percentage of Participants With Breakthrough Hemolysis From Baseline Through Week 32

    Time frame: Baseline through Week 32

    Breakthrough hemolysis was defined as having an LDH ≥ 2 x upper limit of normal (ULN) and having signs or symptoms.

  10. OLTP: Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 32

    Time frame: Week 4 through Week 32

    Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.

  11. OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 32

    Time frame: Day 1 through Week 32

    Adequate control was defined as LDH ≤ 1.5 x ULN from Day 1 through Week 32.

  12. OLTP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 32

    Time frame: Week 8 through Week 32

    Adequate control was defined as LDH ≤ 1.5 x ULN from Week 8 through Week 32.

  13. OLTP: Number of Participants With Adequate Control of Hemolysis at Each Visit

    Time frame: Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225

    Adequate control at a visit was defined as having LDH ≤1.5 x ULN at that visit.

  14. OLTP: Number of Participants With Normalization of Their LDH at Each Visit

    Time frame: Days 1, 8, 15, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225

    Normalization was defined as LDH ≤ 1.0 x ULN at that visit.

  15. OLTP: Average LDH From Baseline Through Week 32

    Time frame: Baseline through Week 32

    The trapezoidal rule was used to calculate area under the curve (AUC). Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period.

  16. OLTP: Average LDH From Week 8 Through Week 32

    Time frame: Week 8 through Week 32

    The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period.

  17. OLTP: Percentage of Participants With Hemoglobin Stabilization From Baseline Through Week 32

    Time frame: Baseline through Week 32

    Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 grams per deciliter (g/dL).

  18. OLTP: Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 32

    Time frame: Week 4 through Week 32

    Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.

  19. OLTP: Change From Baseline in Hemoglobin Levels

    Time frame: Baseline, Week 32

  20. OLTP: Change From Baseline in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score

    Time frame: Baseline, Week 32

    The FACIT-Fatigue is a 13-item, self-reported measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in participants with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Total scores range from 0 to 52, with higher scores indicating a higher quality of life.

  21. OLTP: Change From Baseline in Health Related Quality of Life (HRQoL) as Measured by the Global Health Status Subscale of the European Organization for Research and Treatment of Cancer (EORTC)- Quality of Life Cancer Patients Questionnaire (QLQ) - 30 Scale

    Time frame: Baseline, Week 32

    EORTC-QLQ-C30 is a 30-item self-reported questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. The GHS subscale scores ranged from 0 to 100 with higher scores indicating better quality of life.

  22. OLTP: Change From Baseline in Physical Function (PF) Scores on the EORTC QLQ-C30

    Time frame: Baseline, Week 32

    EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a PF scale. PF subscale scores ranged from 0 to 100 with higher scores indicating better quality of life.

  23. OLTP: Change From Baseline in Total Complement Hemolytic Activity Assay (CH50)

    Time frame: Baseline through Week 32

    This assay assessed the activity of the classical pathway of complement to measure C5 activity.

  24. OLTP and OLEP: Concentration of Total Pozelimab in Serum

    Time frame: Pre-dose Days 28, 56, 84, 112, 140, 168, 196, 224, 392, 588; Post-dose Day 28

  25. OLTP: Concentration of Total Eculizumab in Serum

    Time frame: Pre-dose Days 0, 14, 28, 56, 84, 112, 140, 168, 196, 224

  26. OLTP and OLEP: Concentration of Total Cemdisiran in Plasma

    Time frame: Pre-dose and Post-dose Days 0, 84, 196, 224, 588

  27. OLTP and OLEP: Concentration of Total C5 in Plasma

    Time frame: Pre-dose Days 0, 7, 14, 28, 56, 84, 112, 140, 168, 196, 224, 392, 588

  28. OLTP: Number of Participants With Pozelimab Anti-drug Antibodies (ADA)

    Time frame: Baseline through Week 32

  29. OLTP: Number of Participants With Cemdisiran ADA

    Time frame: Baseline through Week 32

  30. OLTP: Number of Participants Who Received Dose Intensification With TEAEs

    Time frame: Baseline through Week 32

  31. OLEP: Number of Participants With TEAEs

    Time frame: Day 1 through Week 52 of the OLEP

  32. OLEP: Percent Change in LDH From Day 1 Through Week 24 of the OLEP

    Time frame: Day 1 through Week 24 of the OLEP

  33. OLEP: Percent Change in LDH From Day 1 Through Week 52 of the OLEP

    Time frame: Day 1 through Week 52 of the OLEP

  34. OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 24 of the OLEP

    Time frame: Day 1 through Week 24 of the OLEP

  35. OLEP: Percentage of Participants Who Were Transfusion-free From Day 1 Through Week 52 of the OLEP

    Time frame: Day 1 through Week 52 of the OLEP

  36. OLEP: Rate of RBC Transfusions From Day 1 Through Week 24 of the OLEP

    Time frame: Day 1 through Week 24 of the OLEP

    The rate of units of transfusion for a participants was calculated based on the duration of treatment exposure of the participant.

  37. OLEP: Rate of RBC Transfusions From Day 1 Through Week 52 of the OLEP

    Time frame: Day 1 through Week 52 of the OLEP

    The rate of units of transfusion for a participants was calculated based on the duration of treatment exposure of the participant.

  38. OLEP: Number of RBC Units Transfused From Day 1 Through Week 24 of the OLEP

    Time frame: Day 1 through Week 24 of the OLEP

  39. OLEP: Number of RBC Units Transfused From Day 1 Through Week 52 of the OLEP

    Time frame: Day 1 through Week 52 of the OLEP

  40. OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 24 of the OLEP

    Time frame: Day 1 through Week 24 of the OLEP

    Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.

  41. OLEP: Percentage of Participants With Breakthrough Hemolysis From Day 1 Through Week 52 of the OLEP

    Time frame: Day 1 through Week 52 of the OLEP

    Breakthrough hemolysis was defined as having an LDH ≥ 2 x ULN and having signs or symptoms.

  42. OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 24 of the OLEP

    Time frame: Day 1 through Week 24 of the OLEP

    Adequate control was defined as LDH ≤ 1.5 x ULN.

  43. OLEP: Percentage of Participants Who Maintained Adequate Control of Hemolysis From Day 1 Through Week 52 of the OLEP

    Time frame: Day 1 through Week 52 of the OLEP

    Adequate control was defined as LDH ≤ 1.5 x ULN.

  44. OLEP: Number of Participants Who Maintained Adequate Control of Hemolysis at Each Visit in OLEP

    Time frame: Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEP

    Adequate control was defined as LDH ≤ 1.5 x ULN at that visit.

  45. OLEP: Number of Participants With Normalization of Their LDH at Each Visit in OLEP

    Time frame: Baseline, Days 57, 113, 169, 225, 281, 365 of the OLEP

    Normalization was defined as LDH ≤ 1.0 x ULN at that visit.

  46. OLEP: Average LDH From Day 1 Through Week 24 of the OLEP

    Time frame: Day 1 through Week 24 of the OLEP

    The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period.

  47. OLEP: Average LDH From Day 1 Through Week 52 of the OLEP

    Time frame: Day 1 through Week 52 of the OLEP

    The trapezoidal rule was used to calculate AUC. Individual mean LDH is defined as AUC divided by (last assessment date of LDH - first assessment date of LDH) of specific period.

  48. OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 24 of the OLEP

    Time frame: Day 1 through Week 24 of the OLEP

    Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.

  49. OLEP: Percentage of Participants With Hemoglobin Stabilization From Day 1 Through Week 52 of the OLEP

    Time frame: Day 1 through Week 52 of the OLEP

    Hemoglobin stabilization was defined as not receiving an RBC transfusion and having no decrease in hemoglobin level of ≥ 2 g/dL.

  50. OLEP: Change From Baseline in Hemoglobin Levels

    Time frame: Day 1 and Week 24 of the OLEP

  51. OLEP: Change From Baseline in Hemoglobin Levels

    Time frame: Day 1 and Week 52 of the OLEP

  52. OLEP: Change From Baseline in FACIT-Fatigue Score

    Time frame: Day 1 and Week 52 of the OLEP

    The FACIT-Fatigue is a 13-item, self-reported measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Total scores range from 0 to 52, with higher scores indicating a higher quality of life.

  53. OLEP: Change From Baseline in HRQoL as Measured by the Global Health Status Subscale of the EORTC-QLQ-30 Scale

    Time frame: Day 1 and Week 52 of the OLEP

    EORTC-QLQ-C30 is a 30-item self-reported questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. GHS subscale scores ranged from 0 to 100 with higher scores indicating better quality of life.

  54. OLEP: Change From Baseline in PF Scores on the EORTC QLQ-C30

    Time frame: Day 1 and Week 52 of the OLEP

    EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a PF scale. PF subscale scores ranged from 0 to 100 with higher scores indicating better quality of life.

  55. OLEP: Change From Baseline in CH50

    Time frame: Baseline, Week 16, Week 32, Week 52 of the OLEP

    This assay assessed the activity of the classical pathway of complement to measure C5 activity.

  56. OLEP: Number of Participants With Pozelimab ADA

    Time frame: Day 1 through Week 52 of the OLEP

  57. OLEP: Number of Participants With Cemdisiran ADA

    Time frame: Day 1 through Week 52 of the OLEP

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

A Single Arm, Open-Label Study to Assess the Safety, Efficacy, and Pharmacodynamic Effects of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Switch From Eculizumab Therapy

Important dates

Study start
2021
Primary completion
2022
Study completion
2023
First posted
May 17, 2021
Registry last updated
Aug 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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