Skip to main content
OpenTrials
Recruiting

NCT Number: NCT05744921

A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works

This study is researching an experimental treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of this study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH in the long term. The pozelimab + cemdisiran combination may be referred to as "study drugs" in this section.

This study is looking at several other research questions, including:

* How effective is the pozelimab + cemdisiran combination? * What side effects may happen from taking the study drugs? * How much of each study drug is in the blood at different times? * Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)

Recruiting

Interested in participating?

Request Info

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 3

Primary location

Toronto General Hospital, Toronto, Ontario, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

Patients Entering from the Parent Study

  • Patients with PNH who have completed, without permanent discontinuation, study treatment in the parent study (R3918-PNH-2021[NCT05133531]), including the post-Open-label treatment period (OLTP) transition period, if applicable.
  • Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.

Patients Entering with C5 polymorphism

  • Patients with PNH who have a documented C5 polymorphism rendering them refractory to eculizumab or ravulizumab (eg, p.Arg885His, p.Arg885Cys), as described in the protocol
  • Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
  • Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
  • LDH level ≥2 × upper limit of normal (ULN) at the screening visit
  • Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol

Key Exclusion Criteria:

Patients Entering from the Parent Study

  • Significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient
  • Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study

Patients Entering with C5 polymorphism

  • Prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening, except for prior eculizumab or ravulizumab which are not exclusionary
  • Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
  • Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to enrollment and serotype B vaccine within 3 years prior to enrollment as described in the protocol
  • Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
  • Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
  • Known hereditary complement deficiency
  • Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
  • Documented history of liver cirrhosis or patients with liver disease with evidence of current impaired liver function or patients with elevations in Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) (unrelated to PNH or its complications) as described in the protocol

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Treatment and study plan

Pozelimab

Drug

Administered per the protocol

Other names: REGN3918

Cemdisiran

Drug

Administered per the protocol

Other names: ALN-CC5

Primary outcomes

  1. Incidence of treatment-emergent serious adverse events (SAEs)

    Time frame: Up to week 108

    An SAE is any untoward medical occurrence that at any dose:

    • Results in death
    • Is life-threatening
    • Requires in-patient hospitalization or prolongation of existing hospitalization.
    • Results in persistent or significant disability/incapacity
    • Is a congenital anomaly/birth defect.
    • Is an important medical event

  2. Severity of treatment-emergent SAEs

    Time frame: Up to week 108

  3. Incidence of treatment emergent adverse events of special interest (AESIs)

    Time frame: Up to week 108

    An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it

  4. Severity of treatment emergent AESIs

    Time frame: Up to week 108

  5. Incidence of adverse events (AEs) leading to permanent treatment discontinuation

    Time frame: Up to week 108

    Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.

  6. Severity of adverse events (AEs) leading to permanent treatment discontinuation

    Time frame: Up to week 108

    Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.

  7. Percent change from baseline in lactate dehydrogenase (LDH)

    Time frame: Baseline to week 36

Secondary outcomes

  1. Adequate control of hemolysis (LDH ≤1.5 × ULN)

    Time frame: Post-baseline through week 108

  2. Transfusion avoidance

    Time frame: Post-baseline through week 36

    Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

  3. Transfusion avoidance

    Time frame: Post-baseline through week 48

    Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

  4. Transfusion avoidance

    Time frame: Post-baseline through week 76

    Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

  5. Transfusion avoidance

    Time frame: Post-baseline through week 108

    Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

  6. Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)

    Time frame: Post-baseline through week 36

  7. Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)

    Time frame: Post-baseline through week 48

  8. Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)

    Time frame: Post-baseline through week 76

  9. Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)

    Time frame: Post-baseline through week 108

  10. Hemoglobin stabilization

    Time frame: Post-baseline through week 36

    Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL

  11. Hemoglobin stabilization

    Time frame: Post-baseline through week 48

    Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL

  12. Hemoglobin stabilization

    Time frame: Post-baseline through week 76

    Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL

  13. Hemoglobin stabilization

    Time frame: Post-baseline through week 108

    Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL

  14. Percent change in LDH

    Time frame: From baseline to week 48

  15. Percent change in LDH

    Time frame: From baseline to week 76

  16. Percent change in LDH

    Time frame: From baseline to week 108

  17. Change in fatigue

    Time frame: From baseline to week 36

    Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO 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 QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using 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 greater fatigue.

  18. Change in fatigue

    Time frame: From baseline to week 48

    Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO 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 QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.

  19. Change in fatigue

    Time frame: From baseline to week 76

    Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO 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 QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.

  20. Change in fatigue

    Time frame: From baseline to weeks 108

    Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO 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 QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.

  21. Change in physical function (PF) scores on the EORTC QLQ-C30

    Time frame: From baseline to week 36

    EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire)

    EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

  22. Change in PF scores on the EORTC QLQ-C30

    Time frame: From baseline to week 48

    EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire)

    EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

  23. Change in PF scores on the EORTC QLQ-C30

    Time frame: From baseline to week 76

    EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire)

    EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

  24. Change in PF scores on the EORTC QLQ-C30

    Time frame: From baseline to week 108

    EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire)

    EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

  25. Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30

    Time frame: From baseline to week 36

    GHS/QoL (Global Health Status/ Quality of Life)

    Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

  26. Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30

    Time frame: From baseline to week 48

    GHS/QoL (Global Health Status/ Quality of Life)

    Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

  27. Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30

    Time frame: From baseline to week 76

    GHS/QoL (Global Health Status/ Quality of Life)

    Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

  28. Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30

    Time frame: From baseline to week 108

    GHS/QoL (Global Health Status/ Quality of Life)

    Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

  29. Normalization of LDH

    Time frame: From post-baseline through week 108

  30. Rate of red blood cell (RBC) transfusion

    Time frame: Post-baseline through week 36

    Per protocol algorithm

  31. Rate of RBC transfusion

    Time frame: Post-baseline through week 48

    Per protocol algorithm

  32. Rate of RBC transfusion

    Time frame: Post-baseline through week 76

    Per protocol algorithm

  33. Rate of RBC transfusion

    Time frame: Post-baseline through week 108

    Per protocol algorithm

  34. Number of units of RBC transfusion

    Time frame: Post-baseline through week 36

    Per protocol algorithm

  35. Number of units of RBC transfusion

    Time frame: Post-baseline through week 48

    Per protocol algorithm

  36. Number of units of RBC transfusion

    Time frame: Post-baseline through week 76

    Per protocol algorithm

  37. Number of units of RBC transfusion

    Time frame: Post-baseline through week 108

    Per protocol algorithm

  38. Percentage of days with LDH ≤1.5x upper limit of normal (ULN)

    Time frame: Post-baseline through week 36

  39. Percentage of days with LDH ≤1.5x ULN

    Time frame: Post-baseline through week 48

  40. Percentage of days with LDH ≤1.5x ULN

    Time frame: Post-baseline through week 76

  41. Percentage of days with LDH ≤1.5x ULN

    Time frame: Post-baseline through week 108

  42. Change in hemoglobin levels

    Time frame: From baseline to week 36

  43. Change in hemoglobin levels

    Time frame: From baseline to week 48

  44. Change in hemoglobin levels

    Time frame: From baseline to week 76

  45. Change in hemoglobin levels

    Time frame: From baseline to week 108

  46. Change in total complement hemolytic activity assay (CH50)

    Time frame: Through week 108

  47. Percent change in CH50

    Time frame: Through week 108

  48. Concentrations of total pozelimab in serum

    Time frame: Through week 108

  49. Concentrations of cemdisiran in plasma

    Time frame: Through week 24

  50. Incidence of treatment-emergent anti-drug antibodies to pozelimab

    Time frame: Through week 108

  51. Incidence of treatment-emergent anti-drug antibodies to cemdisiran

    Time frame: Through week 108

  52. Concentration of total complement component 5 (C5) in plasma

    Time frame: Through week 108

  53. Percent change of concentration of total C5 in plasma

    Time frame: Through week 108

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Administrator

CONTACT

[email protected]

844-734-6643

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria

Acronym: ACCESS-EXT

Important dates

Study start
2023
Primary completion
2028
Study completion
2028
First posted
Feb 27, 2023
Registry last updated
Jul 30, 2026

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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.