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Long-term treatment for patients with paroxysmal nocturnal hemoglobinuria using pozelimab and cemdisiran

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

PHASE3 · Regeneron Pharmaceuticals · NCT05744921

This study is testing a new combination of two experimental drugs, pozelimab and cemdisiran, to see if they can safely help adults with paroxysmal nocturnal hemoglobinuria over a long period of time.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment202 (estimated)
Ages18 Years and up
SexAll
SponsorRegeneron Pharmaceuticals (industry)
Drugs / interventionseculizumab, ravulizumab, pozelimab
Locations43 sites (Toronto, Ontario and 42 other locations)
Trial IDNCT05744921 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of a combination therapy using two experimental drugs, pozelimab and cemdisiran, in adult patients with paroxysmal nocturnal hemoglobinuria (PNH). It aims to assess how well this treatment works over the long term, including monitoring for side effects and measuring drug levels in the blood. Additionally, the study will investigate whether patients develop antibodies against the drugs, which could impact their effectiveness. Participants must have completed a prior study or have specific genetic markers related to their PNH condition.

Who should consider this trial

Good fit: Ideal candidates include adults with PNH who have completed a prior study treatment or have specific C5 polymorphisms making them resistant to current therapies.

Not a fit: Patients who do not have PNH or those who are not refractory to existing treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new long-term therapeutic option for patients with PNH, particularly those who are refractory to existing therapies.

How similar studies have performed: Other studies have shown promise with similar combination therapies in treating PNH, but this specific combination is being evaluated for the first time.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

Patients Entering from the Parent Study

1. 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.
2. Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.

Patients Entering with C5 polymorphism

1. 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
2. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
3. Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
4. LDH level ≥2 × upper limit of normal (ULN) at the screening visit
5. 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

1. 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
2. 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

1. 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
2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
3. 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
4. Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
5. Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
6. Known hereditary complement deficiency
7. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
8. 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

Where this trial is running

Toronto, Ontario and 42 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Paroxysmal Nocturnal Hemoglobinuria, PNH

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.