Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger
Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger
This study will investigate the efficacy and safety of ravulizumab compared to placebo in
 adult participants with thrombotic microangiopathy (TMA) associated with a trigger.
 Participants will be randomized to receive either ravulizumab plus best supportive care or
 placebo plus best supportive care. The treatment period is 26 weeks followed by a 26-week
 off-treatment follow-up period.
Inclusion Criteria:

 1. 18 years of age or older

 2. Body weight ≥ 30 kilograms

 3. Female participants of childbearing potential and male participants with female
 partners of childbearing potential must use highly effective contraception starting at
 screening and continuing until at least 8 months after the last dose of ravulizumab

 4. Diagnosis of TMA associated with a trigger

 5. Vaccinated against meningococcal infection (Neisseria meningitidis), within 3 years
 prior to, or at the time of, randomization. Participants who initiate study drug
 treatment less than 2 weeks after receiving a meningococcal vaccine must receive
 appropriate prophylactic antibiotics for at least 2 weeks after the vaccination. If
 participant cannot receive the meningococcal vaccine, then participant must be willing
 to receive antibiotic prophylaxis coverage against N. meningitidis during the entire
 Treatment Period and for 8 months following the final dose of study drug. Additional
 vaccination (Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae) may be
 considered based on individual patient condition.

 Exclusion Criteria:

 1. Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)

 2. Postpartum aHUS

 3. Known chronic kidney disease with estimated glomerular filtration rate ≤ 45
 mL/min/1.73 m^2 due to any cause

 4. TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening

 5. Primary and secondary glomerular diseases other than lupus

 6. Diagnosis of primary antiphospholipid antibody syndrome

 7. Shiga toxin-producing Escherichia coli infections including but not limited to Shiga
 toxin-related hemolytic uremic syndrome

 8. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin
 type 1 motif, member 13' (ADAMTS13) deficiency (activity < 5%)

 9. Positive direct Coombs test

 10. Diagnosis of disseminated intravascular coagulation (DIC)

 11. Presence of sepsis according within 7 days prior to or during Screening

 12. Presence of monoclonal gammopathy including but not limited to multiple myeloma

 13. Known bone marrow insufficiency or failure evidenced by cytopenias

 14. Unresolved N. meningitidis infection

 15. History of malignancy within 5 years of Screening with the exception of nonmelanoma
 skin cancer or carcinoma in situ of the cervix that has been treated with no evidence
 of recurrence

 16. Use of any complement inhibitors within the past 3 years