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Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (ACCESS 2)

PHRR220418-004539

R3918-PNH-2022

2022-CT0666

A Randomized, Open-Label Eculizumab and Ravulizumab Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients with Paroxysmal Nocturnal Hemoglobinuria Who are Currently Treated with Eculizumab or Ravulizumab/

This study is a randomized, open-label, eculizumab and ravulizumab-controlled, non-inferiority study. The study plans to enroll approximately 140 patients with PNH who are currently treated with either eculizumab or ravulizumab at the labeled posology. The study consists of an up to 6- week screening period and a 36-week open-label treatment period (OLTP). Patients who complete the OLTP in the anti-C5 standard-of-care arm (ie, randomized to continue eculizumab or ravulizumab) and plan to enroll in the follow-on open-label long-term extension (OLE) study with pozelimab and cemdisiran combination must participate in a post-OLTP transition period.  Patients who discontinue treatment as well as patients who decline enrollment into the follow-on study of the OLE will undergo a safety off-treatment follow up period of up to 52 weeks.

Regime Classification Priority
2017 - 2022 Research in equity and health Drug Discovery and Development
Start Date Duration in Months Target Completion Date Actual Completion Date
0000-00-00 7 2022-10-31 2026-09-18

Ongoing

Institution Classification Region LTO #
Regeneron Pharmaceuticals, Inc. Private Business United States of America
Institution Classification Region LTO #
PPD Pharmaceutical Development Philippines Corporation Private Business NCR CDRR-NCR-CRO-78019
Institution Region
Regeneron Pharmaceuticals, Inc. United States of America
Name E-Mail Institution and Institution Address
Pending info Pending info Pending info
Name E-Mail Institution and Institution Address
Clinical Trial Management Study Director clinicaltrials@regeneron.com Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road Tarrytown, NY 10591
Name Expertise Affiliation
Priscilla B. Caguioa, MD Hematology and Medical Oncology St Lukes Medical Center - Global City
Project Location Institutional Ethics Review Board
St Lukes Medical Center - Global City St. Lukes Medical Center- Institutional Ethics Review Committee

Paroxysmal Nocturnal Hemoglobinuria

To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy

  1. Proportion of patients with transfusion avoidance [ Time Frame: Day 1 through week 36 ]
    Patients who do not receive an RBC transfusion as per protocol algorithm based on post baseline hemoglobin values
  2. Proportion of patients with transfusion avoidance [ Time Frame: Week 4 through week 36 ]
    Patients who do not receive an RBC transfusion as per protocol algorithm based on post baseline hemoglobin values
  3. Proportion of patients with breakthrough hemolysis [ Time Frame: Day 1 through week 36 ]
    Patients with an increase in LDH with concomitant signs or symptoms associated with hemolysis as described in the protocol
  4. Proportion of patients with breakthrough hemolysis [ Time Frame: Week 4 (day 29) through week 36 ]
    Patients with an increase in LDH with concomitant signs or symptoms associated with hemolysis as described in the protocol
  5. Proportion of patients with hemoglobin stabilization [ Time Frame: Day 1 through week 36 ]
    Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level as defined in the protocol
  6. Proportion of patients with hemoglobin stabilization [ Time Frame: Week 4 (day 29) through week 36 ]
    Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level as defined in the protocol
  7. Proportion of patients with adequate control of LDH [ Time Frame: Day 1 through week 36 ]
    Proportion of patients with adequate control of LDH as defined in the protocol
  8. Proportion of patients with adequate control of LDH [ Time Frame: Week 8 (day 57) through week 36 ]
    Proportion of patients with adequate control of LDH as defined in the protocol
  9. Proportion of patients with normalization of LDH [ Time Frame: Day 1 through week 36 ]
    Proportion of patients with normalization of LDH as defined in the protocol
  10. Proportion of patients with normalization of LDH [ Time Frame: Week 8 (day 57) through week 36 ]
    Proportion of patients with normalization of LDH as defined in the protocol
  11. Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale [ Time Frame: From baseline to week 36 ]
    The FACIT-Fatigue is a 13 item, self-administered clinical outcome assessment (COA) 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). Scores range from 0 to 52, with higher scores indicating greater fatigue.
  12. Change in Physical Function (PF) score on the European organization for research and treatment of cancer quality-of-Life questionnaire Core 30 Items (EORTC-QLQ-C30) [ Time Frame: From baseline to week 36 ]
    EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
  13. Change in global health status (GHS)/QoL scale score on the EORTC-QLQ-C30 [ Time Frame: From baseline to week 36 ]
    EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
  14. Rate of RBCs transfused per protocol algorithm [ Time Frame: Day 1 through week 36 ]
    Per protocol algorithm
  15. Rate of RBCs transfused per protocol algorithm [ Time Frame: Week 4 through week 36 ]
    Per protocol algorithm
  16. Number of units of RBCs transfused per protocol algorithm [ Time Frame: Day 1 through week 36 ]
    Per protocol algorithm
  17. Number of units of RBCs transfused per protocol algorithm [ Time Frame: Week 4 through week 36 ]
    Per protocol algorithm
  18. Change in hemoglobin levels [ Time Frame: From baseline to week 36 ]
    Per protocol algorithm
  19. Incidence and severity of treatment emergent serious adverse events (SAEs) [ Time Frame: Up to 88 weeks ]
    Treatment period and safety follow up period
  20. Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest [ Time Frame: Up to 88 weeks ]
    Treatment period and safety follow up period
  21. Incidence and severity TEAEs leading to treatment discontinuation [ Time Frame: Up to 88 weeks ]
    Treatment period and safety follow up period
  22. Change in total CH50 [ Time Frame: From baseline to week 36 ]
  23. Percent change in total CH50 [ Time Frame: From baseline to week 36 ]
  24. Concentration of total C5 in plasma [ Time Frame: Through week 62 ]
    Treatment period and safety follow up period
  25. Concentrations of total pozelimab in serum [ Time Frame: Through week 62 ]
    Treatment period and safety follow up period
  26. Concentrations of total cemdisiran in plasma [ Time Frame: Through week 32 ]
    Treatment period
  27. Concentrations of total eculizumab in serum [ Time Frame: Through week 40 ]
    Treatment period
  28. Concentrations of total ravulizumab in plasma [ Time Frame: Through week 44 ]
    Treatment period
  29. Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab [ Time Frame: Through week 62 ]
    Treatment period and safety follow up period
  30. Incidence of treatment emergent ADAs to cemdisiran [ Time Frame: Through week 62 ]
    Treatment period and safety follow up period

Pending

  • Brazil
  • China
  • Colombia
  • France
  • Germany
  • Greece
  • Hungary
  • Italy
  • Japan
  • Malaysia
  • Mexico
  • North Korea
  • Philippines
  • Poland
  • Romania
  • Singapore
  • Spain
  • Taiwan
  • Thailand
  • United Kingdom
  • United States

Clinical Trial

R3918-PNH-2022

Unspecified

2022-03-18

0000-00-00

1

Unspecified

Unspecified

0000-00-00

Key Inclusion Criteria:

  1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
  2. Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor

Key Exclusion Criteria:

  1. Patients with a screening LDH >1.5 × ULN who have not taken their C5 inhibitor within the labeled dose interval at the dose prior to the screening LDH assessment
  2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
  3. Body weight < 40 kilograms at screening visit
  4. Any use of complement inhibitor therapy other than eculizumab or ravulizumab in the 26 weeks prior to the screening visit or planned use during the study with the exception of study treatments
  5. Not meeting meningococcal vaccination requirements for eculizumab or ravulizumab according to the current local prescribing information (where available) and at a minimum documentation of meningococcal vaccination within 5 years prior to screening visit.
  6. Any contraindication for receiving Neisseria meningitidis vaccination.
  7. Positive for hepatitis B, and/ or hepatitis C as described in the protocol
  8. History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
  9. Participation in another interventional clinical study (except R3918-PNH-2021) or use of any experimental therapy within 30 days before screening visit or within 5 half-lives of that investigational product, whichever is greater, with the exception of eculizumab or ravulizumab.
  10. Patients with functional or anatomic asplenia

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Interventional

Cemdisiran, Eculizumab, Pozelimab, Ravulizumab

Unspecified

None

Randomized

Open Label

Unspecified

Parallel

Treatment

Phase II/III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others
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