Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
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.
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.