Study to Evaluate the Efficacy and Safety of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Condition: Paroxysmal Nocturnal Hemoglobinuria (PNH)
MeSH terms: Hemoglobinuria; Hemoglobinuria, Paroxysmal
Intervention: REGN3918
Intervention description: Single intravenous (IV) dose, then a subcutaneous (SC) dose once weekly (QW).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to demonstrate a reduction in intravascular hemolysis
      by REGN3918 over 26 weeks of treatment in patients with active PNH who are treatment-naive to
      complement inhibitor therapy or have not recently received complement inhibitor therapy.

      The secondary objectives of the study are:

        -  To evaluate the safety and tolerability of REGN3918.

        -  To evaluate the effect of REGN3918 on parameters of intravascular hemolysis

        -  To assess the concentrations of total REGN3918 in serum.

        -  To evaluate the incidence of treatment-emergent anti-drug antibodies to REGN3918 over
           time

        -  To evaluate the effect of REGN3918 on patient-reported outcomes (PROs) measuring fatigue
           and health-related quality of life
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) confirmed by high-sensitivity
             flow cytometry

          -  PNH granulocytes > 10% at screening visit

          -  Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms
             (eg, fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia
             [hemoglobin <10 g/dL], history of a MAVE [including thrombosis], dysphagia, or
             erectile dysfunction) or history of red blood cell (RBC) transfusion due to PNH within
             3 months of screening.

          -  Lactate dehydrogenase (LDH) level ≥ 2 × upper limit of normal (ULN) at screening
             visit.

        Key Exclusion Criteria:

          -  Prior treatment with a complement inhibitor either within 6 months prior to screening
             visit or at any time where the patient was refractory to complement inhibitor therapy,
             in the opinion of the investigator (with the exception of eculizumab refractory
             patients due to the C5 variant R885H/C)

          -  History of bone marrow transplantation

          -  Body weight < 40 kilograms at screening visit

          -  Peripheral blood absolute neutrophil count (ANC) <500/μL [<0.5 x 109/L] or peripheral
             blood platelet count <50,000/μL

          -  Documented history of systemic fungal disease or unresolved tuberculosis, or evidence
             of active or latent tuberculosis infection (LTBI) during screening period

          -  Any contraindication for receiving Neisseria meningitidis vaccination and antibiotic
             prophylaxis therapy as recommended in the study

          -  Any active, ongoing infection within 2 weeks of screening or during the screening
             period

          -  Any clinically significant abnormality identified at the time of screening that in the
             judgment of the Investigator or any sub-Investigator would preclude safe completion of
             the study or constrain endpoints assessment such as major systemic diseases, or
             patients with short life expectancy

          -  Women who are pregnant, breastfeeding, or who have a positive pregnancy test at
             screening visit or day 1

        NOTE: Other protocol defined Inclusion/Exclusion criteria apply.