A C5 inhibitor-controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 12

Inclusion Criteria

1. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes described in the protocol
2. Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
3. LDH level >=2xULN at the screening visit
4. Other Inclusion Criteria Apply.

Exclusion Criteria

1. Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening.
2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant.
3. Body weight <40 kilograms at screening visit.
4. Planned use of any complement inhibitor therapy other than study drugs during the treatment period.
5. Not meeting meningococcal vaccination requirements for ravulizumab (Cohort A) or eculizumab (Cohort B) 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. Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab [Cohort A] or eculizumab [Cohort B] prescribing information, where available, or national guidelines/local practice or if necessary when vaccination is less than 2 weeks from study treatment initiation).
8. Any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period.
9. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases.
10. Other Exclusion Criteria Apply.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Cohort A:<br>Percent change in lactate dehydrogenase (LDH) [Time Frame: From baseline to week 26]<br><br>Cohort B:<br>1. Maintenance of adequate control of hemolysis [Time Frame: week 8 through week 26, inclusive]<br>2. Transfusion avoidance [Time Frame: Day 1 through week 26]

Secondary Outcome Measures

Name	Time	Method

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