AN OPEN-LABEL, MULTI-CENTER CONTROLLED CLINICAL TRIAL OF ECULIZUMAB IN ADOLESCENT PATIENTS WITH PLASMA THERAPY-RESISTANT ATYPICAL HEMOLYTIC-UREMIC SYNDROME (AHUS)

1. Male or female patients from 12 and up to 18 years of age who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS). Patients may be newly diagnosed, experiencing a relapse of the disease, or having a post-transplant recurrence of the disease.
2. Patients must exhibit a decrease in platelet count despite at least 4 Plasma Therapy (PT) treatments in the 1 week immediately prior to screening. At screening, platelet count must be < 150 x 10 9/L and at least 25% lower than the average of 3 platelet counts obtained during remission and at least 1 month apart over the 12 months prior to screening (designated the *average remission platelet count*).
3. If historical counts are not available, platelet count at screening must be < 75 x 10 9/L despite PT treatment administration of at least 4 PT treatments in the 1 week immediately prior to screening.
4. Known complement regulatory protein genetic abnormality, i.e., a mutation in
Complement Protein 3, factor H or associated factor, factor I, or membrane cofactor
protein 1 (MCP-1) or known Factor B gain-of-function mutation, or known anti-CFH
antibody (*aHUS lesions*).
• Patients diagnosed with aHUS with any of these aHUS lesions are eligible and will be assigned to one of the following parallel categories during the treatment period of the trial:
* (Category 1) Complement Protein 3 or factor H or factor I functional deficiency
or abnormal factor interaction (C3/CFH/CFI FFP Group);
* (Category 2) Factor B Gain of Function;
* (Category 3) Anti-CFH Antibody (Anti-CFH Group);
* (Category 4) MCP-1 deficiency (MCP-1 Group);
5. Patients diagnosed with HUS of the atypical type without documented complement regulatory protein genetic abnormality or known anti-CFH antibody are eligible if other etiologies of HUS have been ruled out as confirmed in the Exclusion Criteria (i.e., including Shiga-toxin negative, non-infectious, non-drug-exposure-related [e.g., cyclosporine]), no known HIV positivity, and anti-phospholipid antibody negative). Thrombotic thrombocytopenic purpura also must be ruled out (i.e., ADAMTS-13 activity must be > 5%; see Exclusion Criteria). Patients meeting these conditions will be assigned to Category 5. In addition, these patients will undergo genetic testing to determine if a mutation can be identified. If a mutation is identified, the patient will be reassigned to the appropriate category.
6. Lactate dehydrogenase (LDH) level >= ULN;
7. Creatinine level >= ULN for age (patients requiring acute dialysis for acute renal failure also eligible).
8. Sexually active women of childbearing potential must be practicing an effective, reliable and medically acceptable contraceptive regimen during the entire duration of the study, including the follow-up period.
9. Patient's parents/legal guardian must be willing and able to give written informed consent and patients must be willing to give written informed assent.
10. Able and willing to comply with study procedures.

1. ADAMTS-13 inhibitor or deficiency (i.e., ADAMTS-13 activity <5%) as measured at the screening visit.
2. Malignancy.
3. Typical HUS (Shiga toxin +).
4. Known HIV infection.
5. Identified drug exposure-related HUS.
6. Infection-related HUS.
7. Renal function status requiring chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy).
8. Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within 7 days of the screening visit and not treated with antibiotics to which the organism is sensitive.
9. Presence or suspicion of active and untreated systemic bacterial infection that, in the opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease.
10. Pregnancy or lactation.
11. Unresolved meningococcal disease.
12. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
13. Any medical or psychological condition that, in the opinion of the investigator, could increase the patient*s risk by participating in the study or confound the outcome of the study.
14. Patients receiving IVIg or Rituximab therapy.
15. Patients receiving other immunosuppressive therapies such as steroids, mTOR inhibitors or FK506 inhibitors are excluded unless: [1] part of a post-transplant anti-rejection regime, [2] patient has confirmed anti-CFH antibody requiring immunosuppressive therapy and [3] dose of such medications have been unchanged for at least 4 weeks prior to the screening period.
16. Patients receiving Erythrocyte Stimulating Agents (ESAs) unless already on a stable dose for at least 4 weeks prior to the screening period.
17. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedures beginning 4 weeks prior to screening and throughout the entire trial.