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

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ClinicalTrials.gov Identifier: NCT04811716
Recruitment Status : Completed
First Posted : March 23, 2021
Last Update Posted : November 27, 2023
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Description
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Brief Summary:

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

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria Drug: Pozelimab Drug: Cemdisiran Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : July 29, 2021
Actual Primary Completion Date : October 25, 2022
Actual Study Completion Date : October 18, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Pozelimab Q4W + Cemdisiran Drug: Pozelimab
Administered Sub-cutaneous (SC) per protocol
Other Name: REGN3918

Drug: Cemdisiran
Administered SC per protocol
Other Name: ALN-CC5
Experimental: Pozelimab Q2W + Cemdisiran Drug: Pozelimab
Administered Sub-cutaneous (SC) per protocol
Other Name: REGN3918

Drug: Cemdisiran
Administered SC per protocol
Other Name: ALN-CC5


Outcome Measures
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Primary Outcome Measures :
  1. Incidence and severity of treatment emergent adverse events (TEAEs) [ Time Frame: Through Week 28 ]
    Open Label Treatment Period (OLTP)


Secondary Outcome Measures :
  1. Percent change of 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)

  2. Maintenance of adequate control of hemolysis [ Time Frame: Day 1 through Week 28 ]
    OLTP

  3. Maintenance of adequate control of hemolysis [ Time Frame: Week 4 through Week 28 ]
    OLTP

  4. Adequate control of hemolysis [ Time Frame: Day 1 through Week 28 ]
    OLTP

  5. Normalization of LDH [ Time Frame: Day 1 through Week 28 ]
    OLTP

  6. Area under the curve (AUC) of LDH over time [ Time Frame: Day 1 through Week 28 ]
    OLTP

  7. AUC of LDH over time [ Time Frame: Week 4 through Week 28 ]
    OLTP

  8. Breakthrough hemolysis [ Time Frame: Baseline through Week 28 ]
    OLTP

  9. Hemoglobin stabilization [ Time Frame: Baseline through Week 28 ]
    OLTP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels

  10. Change in hemoglobin levels [ Time Frame: Baseline to Week 28 ]
    OLTP

  11. Transfusion avoidance [ Time Frame: Baseline to Week 28 ]
    OLTP Not requiring a RBC transfusion as per protocol algorithm

  12. Rate of RBCs transfused [ Time Frame: Baseline to Week 28 ]
    OLTP

  13. Number of units of RBCs transfused [ Time Frame: Baseline to Week 28 ]
    OLTP

  14. Change in CH50 [ Time Frame: Baseline to Week 28 ]
    OLTP

  15. Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale [ Time Frame: Baseline 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

  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) [ Time Frame: Baseline to Week 28 ]
    OLTP EORTC QLQ-C30 comprises 30 items (i.e. single questions), 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. The remaining six single-item (dyspnoea, appetite loss, sleep disturbance, constipation, diarrhoea and the financial impact) scales assess symptoms. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).

  17. Change in physical function (PF) scores on the EORTC QLQ-C30 [ Time Frame: Baseline to Week 28 ]
    OLTP

  18. Concentrations of total pozelimab in serum [ Time Frame: Up to Week 28 ]
    OLTP

  19. Concentrations of cemdisiran in plasma [ Time Frame: Up to Week 28 ]
    OLTP

  20. Change from baseline in concentration of total C5 [ Time Frame: Baseline through Week 28 ]
    OLTP

  21. Incidence of pozelimab anti-drug antibody (ADA) responses over time [ Time Frame: Up to Week 28 ]
    OLTP

  22. Incidence of cemdisiran anti-drug antibody (ADA) responses over time [ Time Frame: Up to Week 28 ]
    OLTP

  23. Incidence and severity of TEAEs for participants who received treatment intensification [ Time Frame: Through Week 28 ]
    OLTP

  24. Change of LDH [ Time Frame: Day 1 to Week 24 ]
    Optional Open-Label Extension Period (OLEP)

  25. Percent change of LDH [ Time Frame: Day 1 to Week 24 ]
    OLEP

  26. Change of LDH [ Time Frame: Day 1 to Week 52 ]
    OLEP

  27. Percent change of LDH [ Time Frame: Day 1 to Week 52 ]
    OLEP

  28. Maintenance of adequate control of hemolysis [ Time Frame: Day 1 through Week 24 ]
    OLEP

  29. Maintenance of adequate control of hemolysis [ Time Frame: Day 1 through Week 52 ]
    OLEP

  30. Adequate control of hemolysis [ Time Frame: Day 1 through Week 52 ]
    OLEP

  31. Normalization of LDH [ Time Frame: Day 1 through week 52 ]
  32. AUC of LDH over time [ Time Frame: Day 1 through Week 52 ]
    OLEP

  33. Breakthrough hemolysis [ Time Frame: Day 1 through Week 24 ]
    OLEP

  34. Breakthrough hemolysis [ Time Frame: Day 1 through Week 52 ]
    OLEP

  35. Hemoglobin stabilization [ Time Frame: Day 1 through Week 24 ]
    OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels

  36. Hemoglobin stabilization [ Time Frame: Day 1 through Week 52 ]
    OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels

  37. Change in hemoglobin levels [ Time Frame: Day 1 to Week 24 ]
    OLEP

  38. Change in hemoglobin levels [ Time Frame: Day 1 to Week 52 ]
    OLEP

  39. Transfusion avoidance [ Time Frame: Day 1 through Week 24 ]
    OLEP Not requiring a RBC transfusion as per protocol algorithm

  40. Transfusion avoidance [ Time Frame: Day 1 through Week 52 ]
    OLEP Not requiring a RBC transfusion as per protocol algorithm

  41. Rate of RBCs transfused [ Time Frame: Day 1 to Week 24 ]
    OLEP

  42. Rate of RBCs transfused [ Time Frame: Day 1 to Week 52 ]
    OLEP

  43. Number of units of RBCs transfused [ Time Frame: Day 1 to Week 24 ]
    OLEP

  44. Number of units of RBCs transfused [ Time Frame: Day 1 to Week 52 ]
    OLEP

  45. Change in CH50 [ Time Frame: Day 1 to Week 16 ]
    OLEP

  46. Change in CH50 [ Time Frame: Day 1 to Week 24 ]
    OLEP

  47. Change in CH50 [ Time Frame: Day 1 to Week 52 ]
    OLEP

  48. Percent change in CH50 [ Time Frame: Day 1 to Week 16 ]
    OLEP

  49. Percent change in CH50 [ Time Frame: Day 1 to Week 24 ]
    OLEP

  50. Percent change in CH50 [ Time Frame: Day 1 to Week 52 ]
    OLEP

  51. Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale [ Time Frame: Day 1 to Week 52 ]
    OLEP

  52. Change in GHS/QoL on the EORTC QLQ-C30 [ Time Frame: Day 1 to Week 52 ]
    OLEP

  53. Change in PF scores on the EORTC QLQ-C30 [ Time Frame: Day 1 to Week 52 ]
    OLEP

  54. Incidence and severity of TEAEs [ Time Frame: Up to Week 52 ]
    OLEP

  55. Concentrations of total pozelimab in serum [ Time Frame: Up to Week 52 ]
    OLEP

  56. Concentrations of total C5 [ Time Frame: Up to Week 52 ]
    OLEP

  57. Concentrations of cemdisiran in plasma [ Time Frame: Up to Week 52 ]
    OLEP

  58. Incidence of pozelimab anti-drug antibody (ADA) responses over time [ Time Frame: Up to Week 52 ]
    OLEP

  59. Incidence of cemdisiran anti-drug antibody (ADA) responses over time [ Time Frame: Up to Week 52 ]
    OLEP


Eligibility Criteria
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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

Key Inclusion Criteria:

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

Key Exclusion Criteria:

  1. 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
  2. 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
  3. Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol
  4. 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
  5. Known hypersensitivity to cemdisiran or any component of cemdisiran formulation

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Contacts and Locations
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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): NCT04811716


Locations
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Hong Kong
Prince of Wales Hospital
Hong Kong, New Territories, Hong Kong, 550540
Hungary
D l Pesti Centrumk rh z Orsz gos Hematol giai s Infektol giai Int zet
Budapest, Nagyvárad Tér 1, Hungary, 1907
Korea, Republic of
Samsung Medical Center
Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
Pusan National University Hospital
Busan, Korea, Republic of, 49241
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Yonsei University College of Medicine, Severance Hospital
Seoul, Korea, Republic of, 3722
Ewha Womans University Medical Centre
Seoul, Korea, Republic of, 7985
Malaysia
Hospital Miri
Miri, Sarawak, Malaysia, 98000
Hospital Sibu
Sibu, Sarawak, Malaysia, 96000
Hospital Sultanah Nur Zahirah
Kuala Terengganu, Terengganu, Malaysia, 20400
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 10002
Chang Gung Memorial Hospital
Taoyuan City, Taiwan, 333
United Kingdom
St. James's University Hospital
Leeds, West Yorkshire, United Kingdom, LS97TF
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
More Information
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04811716    
Other Study ID Numbers: R3918-PNH-2092
2020-005005-17 ( EudraCT Number )
First Posted: March 23, 2021    Key Record Dates
Last Update Posted: November 27, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Regeneron Pharmaceuticals:
PNH
Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
 Male Urogenital Diseases
Urological Manifestations
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases