ALXN1210 (Ravulizumab) Versus Eculizumab in Complement Inhibitor Treatment-Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Condition: Paroxysmal Nocturnal Hemoglobinuria (PNH)
MeSH terms: Hemoglobinuria; Hemoglobinuria, Paroxysmal
Intervention: Ravulizumab; Eculizumab
Intervention description: All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to <60 kilogram (kg): 2400 mg was given as a single loading dose, followed by 3000 mg as maintenance dose. For participants weighing ≥60 to <100 kg: 2700 mg was given as a loading dose, followed by 3300 mg as maintenance dose. For participants weighing ≥100 kg: 3000 mg was given as a loading dose, followed by 3600 mg as maintenance dose.; All treatments were given as IV infusions. Participants were administered induction doses of 600 mg followed by maintenance doses of 900 mg.
Intervention MeSH terms: Eculizumab; Ravulizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 270.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study was to assess the noninferiority of ravulizumab compared to
      eculizumab in adult participants with PNH who had never been treated with a complement
      inhibitor (treatment-naïve).
    

Eligibility criteria:

        Criteria For Patient Cohort Originally Enrolled in ALXN1210-PNH-301 Study:

        Inclusion Criteria:

          1. Male or female ≥18 years of age.

          2. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.

          3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months
             of screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea),
             anemia (hemoglobin <10 gram/deciliter), history of a major adverse vascular event
             (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red
             blood cells (pRBC) transfusion due to PNH.

          4. Lactate dehydrogenase (LDH) level ≥1.5 times the upper limit of normal at screening.

          5. Documented meningococcal vaccination not more than 3 years prior to, or at the time
             of, initiating study treatment.

          6. Female participants of childbearing potential must use highly effective contraception
             starting at screening and continuing until at least 8 months after the last dose of
             ravulizumab.

          7. Willing and able to give written informed consent and comply with study visit
             schedule.

        Exclusion Criteria:

          1. Treatment with a complement inhibitor at any time.

          2. History of bone marrow transplantation.

          3. Body weight <40 kg.

          4. Females who are pregnant, breastfeeding, or who have a positive pregnancy test at
             screening or Day 1.

          5. Participation in another interventional clinical study or use of any experimental
             therapy within 30 days before initiation of study drug on Day 1 in this study or
             within 5 half-lives of that investigational product, whichever is greater.

          6. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease
             that, in the opinion of the investigator or sponsor, would preclude participation.

          7. Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal
             bleed, severe congestive heart failure, anticipated need for major surgery within 6
             months of randomization, coexisting chronic anemia unrelated to PNH).

        Eligibility Criteria For Roll-over Cohort:

          1. All participants regardless of age, who are currently receiving ALXN1210 IV in an
             ongoing ALXN1210 study in patients with PNH

          2. Participants must be willing and able to give written informed consent and to comply
             with all Extension study visits and procedures, including the use of any data
             collection device(s) to directly record patient data

          3. Females of childbearing potential and male patients with female partners of
             childbearing potential must use highly effective contraception continuing until at
             least 8 months after the last dose of ravulizumab.