A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition
Condition: Paroxysmal Nocturnal Hemoglobinuria
MeSH terms: Hemoglobinuria; Hemoglobinuria, Paroxysmal
Intervention: Crovalimab
Intervention description: Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 and 100kg) or 1500 mg IV (for participants with body weight >=100kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, it will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants with body weight between 40 and 100kg) or 1020 mg SC (for participants with body weight >=100kg). Dosing schedule will be as described above.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      This study will enrol participants aged 12 years or older with a body weight >= 40 kilograms
      (kg) diagnosed with PNH who have not been previously treated with complement inhibitor
      therapy. Approximately 50 participants will be treated with Crovalimab for at least 24 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Body weight >= 40 kg at screening.

          -  Willingness and ability to comply with all study visits and procedures.

          -  Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.

          -  LDH Levels >= 2x the ULN at screening.

          -  Participants who have at least four transfusions during 12 months prior to screening
             (documented in the medical record).

          -  Presence of one or more of the following PNH-related signs or symptoms within 3 months
             of screening.

          -  Vaccination against Neisseria meningitidis serotypes A, C, W, and Y < 3 years prior to
             initiation of study treatment (Day 1)

          -  Vaccination against Haemophilius influenzae type B and Streptococcus pneumonia
             according to national vaccination recommendations.

          -  For participants receiving other therapies (e.g., immunosuppressants,
             corticosteroids): stable dose for >= 28 days prior to screening and up to the first
             drug administration.

          -  Adequate hepatic and renal function.

          -  Women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraception during the treatment period and for 46
             weeks (approximately 10.5 months) after the final dose of crovalimab.

          -  Platelet count >=30,000 cubic millimeter (mm^3) at screening

          -  ANC > 500/μl at screening

        Exclusion Criteria:

          -  Current or previous treatment with a complement inhibitor.

          -  History of allogeneic bone marrow transplantation.

          -  History of Neisseria meningitidis infection within 6 months prior to screening and up
             to first drug administration.

          -  Known or suspected immune or hereditary complement deficiency.

          -  Known HIV infection with CD4 count < 200 cells per microlitre (cells/µl) within 24
             weeks prior to screening.

          -  Infection requiring hospitalization or treatment with intravenous (IV) antibiotics
             within 28 days prior to screening and up to the first drug administration, or oral
             antibiotics within 14 days prior to screening and up to the first drug administration.

          -  Active systemic bacterial, viral, or fungal infection within 14 days before first drug
             administration.

          -  Presence of fever (>= 38˚C) within 7 days before the first drug administration.

          -  Splenectomy < 6 months before screening.

          -  History of malignancy within 5 years prior to screening and up to the first drug
             administration.

          -  Pregnant or intending to become pregnant during the study or within 46 weeks (10.5
             months) after the final dose of study treatment.

          -  Participation in another interventional treatment study with an investigational agent
             or use of any experimental therapy within 28 days of screening or within 5 half-lives
             of that investigational product, whichever is greater.