Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
Condition: Atypical Hemolytic Uremic Syndrome (aHUS)
MeSH terms: Azotemia; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome; Syndrome; Hemolysis
Intervention: Ravulizumab
Intervention description: Participant received weight-based dosages for 26 weeks during the Initial Evaluation Period. Participants received a loading dose on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter for participants weighing ≥ 20 kg, or once every 4 weeks for participant weighing < 20 kg.
Intervention MeSH terms: Ravulizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to assess the efficacy of ravulizumab to control disease activity
      in children and adolescents with aHUS who have not previously used a complement inhibitor
      (complement inhibitor treatment-naïve), as well as in complement inhibitor-experienced
      (eculizumab-experienced) adolescent participants.
    

Eligibility criteria:

        Inclusion Criteria:

        Complement Inhibitor Treatment Naïve:

          1. Participants from birth up to <18 years of age and weighing ≥5 kilograms (kg) at the
             time of consent.

          2. Participants had not been previously treated with complement inhibitors.

          3. Evidence of thrombotic microangiopathy (TMA), including low platelet count, hemolysis
             (breaking of red blood cells inside of blood vessels), and decreased kidney function.

          4. Documented meningococcal vaccination not more than 3 years prior to dosing, and
             vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.

          5. Female participants of childbearing potential and male participants with female
             partners of childbearing potential must have used highly effective contraception
             starting at screening and continuing until at least 8 months after the last dose of
             ravulizumab.

        Eculizumab Experienced:

          1. Participants between 12 and <18 years of age (non-Japanese sites) or <18 years of age
             (Japanese sites) who had been treated with eculizumab according to the labelled dosing
             recommendation for aHUS for at least 90 days prior to screening.

          2. Participants with documented diagnosis of aHUS.

          3. Participants with clinical evidence of response to eculizumab indicated by stable TMA
             parameters at screening.

          4. Documented meningococcal vaccination not more than 3 years prior to dosing, and
             vaccination against Streptococcus pneumoniae and Haemophilus influenzae type b.

          5. Females of childbearing potential and male participants with female partners of
             childbearing potential must have used highly effective contraception starting at
             screening and continuing until at least 8 months after the last dose of ravulizumab.

        Exclusion Criteria:

          1. Known familial or acquired ADAMTS13 ("a disintegrin and metalloproteinase with a
             thrombospondin type 1 motif, member 13") deficiency (activity <5%).

          2. Known Shiga toxin-related hemolytic uremic syndrome.

          3. Positive direct Coombs test.

          4. Females who planned to become pregnant during the study or were currently pregnancy or
             breastfeeding.

          5. Identified drug exposure-related hemolytic uremic syndrome.

          6. Bone marrow transplant/hematopoietic stem cell transplant within the last 6 months
             prior to the start of screening.

          7. Hemolytic uremic syndrome related to known genetic defects of cobalamin C metabolism.

          8. Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or
             antiphospholipid antibody positivity or syndrome.

          9. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy
             for end-stage kidney disease.

         10. For eculizumab-experienced participants, prior use of complement inhibitors other than
             eculizumab.

         11. For eculizumab-experienced participants, any known abnormal TMA parameters within 90
             days prior to screening.