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Completed

NCT Number: NCT04811716

Pozelimab and Cemdisiran Combination Treatment in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy

The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP)

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 total complement hemolysis activity (CH50) * To evaluate the effect of the combination treatment on hemoglobin levels * To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements * To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life * To assess the concentrations of total pozelimab in serum and total complement component (C) 5 and cemdisiran in plasma * To assess immunogenicity to pozelimab and cemdisiran * To evaluate the long-term safety and efficacy of pozelimab and cemdisiran in an optional open-label extension period (OLEP) * To assess safety after treatment intensification with pozelimab and cemdisiran

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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

Prince of Wales Hospital, Hong Kong, New Territories

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Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

  • Participants with PNH who are receiving treatment with pozelimab monotherapy in the R3918- PNH-1868 study (NCT04162470)

Key Exclusion Criteria:

  • Documented, positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as defined in the protocol
  • Participants with documented history of liver cirrhosis or participants with liver disease with evidence of currently impaired liver function; or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) as described in the protocol
  • Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol
  • Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the participant unsuitable for enrollment or would jeopardize the safety of the participant
  • Known hypersensitivity to cemdisiran or any component of cemdisiran formulation

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Treatment and study plan

Pozelimab

Drug

Administered Sub-cutaneous (SC) per protocol

Other names: REGN3918

Cemdisiran

Drug

Administered SC per protocol

Other names: ALN-CC5

Primary outcomes

  1. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

    Time frame: Through Week 28

    Open Label Treatment Period (OLTP)

Secondary outcomes

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

    Time frame: End of treatment period, approximately 28 Weeks

    OLTP Pre-treatment (mean of LDH values prior to combination dosing); End-of-treatment (mean of LDH value at week 24- through week 28); percentage of change in Upper Limit of Normal (xULN).

  2. Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) through Week 28

    OLTP Adequate control of hemolysis is defined as LDH values ≤1.5 × Upper limit of normal (ULN) from baseline (day 1) to week 28

  3. Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28

    Time frame: Week 4 through Week 28

    OLTP

  4. Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28

    Time frame: Day 1 through Week 28

    OLTP; Adequate control at a visit is defined as having LDH <=1.5 x ULN at that visit

  5. Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) through Week 28

    OLTP; Normalization of LDH was defined as LDH ≤1.0 × ULN at each visit

  6. Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) through Week 28

    OLTP

  7. Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28

    Time frame: Week 4 through Week 28

    OLTP

  8. Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) through Week 28

    OLTP

    Breakthrough hemolysis is defined as an increase in LDH with concomitant signs or symptoms associated with hemolysis:

    • An increase in LDH occurs when:
    • LDH ≥2 × ULN if pre-treatment LDH is ≤1.5 × ULN or
    • LDH ≥2 × ULN after initial achievement of LDH ≤1.5 × ULN if pre-treatment LDH is >1.5 × ULN Signs or symptoms should correspond to those known to be associated with intravascular hemolysis due to Paroxysmal nocturnal hemoglobinuria (PNH) limited to the following: new onset or worsening fatigue, headache, dyspnea, hemoglobinuria, abdominal pain, scleral icterus, erectile dysfunction, chest pain, confusion, dysphagia, anemia including hemoglobin value significantly lower (ie, ≥2g/dL decrease) compared to patient's known baseline hemoglobin values, and thrombotic event.

  9. Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) through Week 28

    OLTP Hemoglobin stabilization was defined as participants who did not receive an RBC transfusion and had no decrease in hemoglobin level of ≥2 grams per deciLiter (g/dL).

  10. Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) to Week 28

    OLTP

  11. Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) to Week 28

    OLTP Not requiring a red blood cell (RBC) transfusion as per protocol algorithm

  12. Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28

    Time frame: Baseline (Day 1) to Week 28

    OLTP Rate of RBCs transfused is defined as number of events per person-years of treatment. For each participant, the participant-years are the time from first dose date to week 28 (or early terminations visit if subject discontinued the study early) in the OLTP.

  13. Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) to Week 28

    OLTP

  14. Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) to Week 28

    OLTP

  15. Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) to Week 28

    OLTP FACIT fatigue is a 13-item scale and for each item 4 is not at all fatigued to 0 very much fatigued. Higher FACIT-Fatigue scores indicate less fatigue (scores range from 0-52). A 5-point change is considered clinically meaningful.

  16. Change in Global Health Status/Quality of Life Scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire Core 30 Items (EORTC QLQ-C30) From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) to Week 28

    OLTP EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.

  17. Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28

    Time frame: Baseline (Day 1) to Week 28

    OLTP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.

  18. Concentrations of Total Pozelimab in Serum on Week 28

    Time frame: On Week 28

    OLTP

  19. Concentrations of Cemdisiran in Plasma on Week 28

    Time frame: On Week 28

    OLTP

  20. Concentrations of Total C5 on Week 28

    Time frame: On Week 28

    OLTP

  21. Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time

    Time frame: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])

    OLTP and OLEP

  22. Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time

    Time frame: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])

    OLTP and OLEP

  23. Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification

    Time frame: Through Week 28

    OLTP No participants received dose intensification during the study; Therefore, assessment of the safety of pozelimab + cemdisiran combination therapy in participants requiring dose intensification was not conducted.

  24. Change of LDH From Baseline (Day 1e) to Week 24e

    Time frame: Baseline (Day 1e) to Week 24e

    Optional Open-Label Extension Period (OLEP)

  25. Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e

    Time frame: Baseline (Day 1e) to Week 24e

    OLEP; Percentage of change for units per liter (U/L)

  26. Change of LDH From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP

  27. Percent Change of LDH From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP

  28. Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e

    Time frame: Baseline (Day 1e) through Week 24e

    OLEP

  29. Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e

    Time frame: Baseline (Day 1e) through Week 52e

    OLEP

  30. Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e

    Time frame: Baseline (Day 1e) through Week 52e

    OLEP Adequate control at a visit is defined as having LDH <=1.5 x ULN at that visit

  31. Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e

    Time frame: Baseline (Day 1e) through week 52e

    OLEP

  32. Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e

    Time frame: Baseline (Day 1e) through Week 52e

    OLEP

  33. Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e

    Time frame: Baseline (Day 1e) through Week 24e

    OLEP

  34. Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e

    Time frame: Baseline (Day 1e) through Week 52e

    OLEP

  35. Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e

    Time frame: Baseline (Day 1e) through Week 24e

    OLEP Participants who did not receive RBC transfusion and had no decrease in hemoglobin levels

  36. Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e

    Time frame: Baseline (Day 1e) through Week 52e

    OLEP Participants who did not receive RBC transfusion and had no decrease in hemoglobin levels

  37. Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e

    Time frame: Baseline (Day 1e) to Week 24e

    OLEP

  38. Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP

  39. Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e

    Time frame: Baseline (Day 1e) through Week 24e

    OLEP Not requiring a RBC transfusion as per protocol algorithm

  40. Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP Not requiring a RBC transfusion as per protocol algorithm

  41. Rate of RBCs Transfused From Baseline (Day 1e) to Week 24e

    Time frame: Baseline (Day 1e) to Week 24e

    OLEP

  42. Rate of RBCs Transfused From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP

  43. Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 24e

    Time frame: Baseline (Day 1e) to Week 24e

    OLEP

  44. Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP

  45. Change in CH50 From Baseline (Day 1e) to Week 16e

    Time frame: Baseline (Day 1e) to Week 16e

    OLEP

  46. Change in CH50 From Baseline (Day 1e) to Week 24e

    Time frame: Baseline (Day 1e) to Week 24e

    OLEP

  47. Change in CH50 From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP

  48. Percent Change in CH50 From Baseline (Day 1e) to Week 16e

    Time frame: Baseline (Day 1e) to Week 16e

    OLEP

  49. Percent Change in CH50 From Baseline (Day 1e) to Week 24e

    Time frame: Baseline (Day 1e) to Week 24e

    OLEP

  50. Percent Change in CH50 From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP

  51. Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP; The FACIT-Fatigue is a 13-item, self-administered assessment of 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 QoL in participants with cancer and other chronic illnesses. The FACIT-Fatigue items are measured with a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating less fatigue. A 5-point change is considered clinically meaningful.

  52. Change in GHS/QoL on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.

  53. Change in PF Scores on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e

    Time frame: Baseline (Day 1e) to Week 52e

    OLEP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.

  54. Percentage of Participants With TEAEs Up to Week 52

    Time frame: Up to Week 52

    OLEP

  55. Concentrations of Total Pozelimab in Serum on Week 52

    Time frame: On Week 52

    OLEP

  56. Concentrations of Total C5 on Week 52

    Time frame: On Week 52

    OLEP

  57. Concentrations of Cemdisiran in Plasma on Week 52

    Time frame: On Week 52

    OLEP

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

A Randomized, Open-label, Two-arm Study to Evaluate the Safety, Efficacy, and Pharmacodynamic Effects of Pozelimab and Cemdisiran Combination Treatment in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy

Important dates

Study start
2021
Primary completion
2022
Study completion
2023
First posted
Mar 23, 2021
Registry last updated
Apr 8, 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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