An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
The primary purpose is to assess the efficacy and safety of eculizumab in pediatric patients
 with aHUS to control TMA as characterized by thrombocytopenia, hemolysis and renal
 impairment.
Inclusion:

 1. Patient's parent/legal guardian must have been willing and able to give written
 informed consent and the patient must have been willing to give written informed
 assent (if applicable as determined by the central IRB/IEC).

 2. Pediatric patients with aHUS: Patients could have been newly diagnosed, or with
 previously diagnosed disease, or post-kidney transplant with the disease.

 3. Patients one month to 18 years and body weight ≥ 5kg.

 4. Platelet count at screening and baseline visit must have been below lower limit of
 normal (<LLN). If screening visit and baseline visit are combined into one day, an
 additional platelet count value obtained at least 24 hours before screening/baseline
 sample must also be <LLN.

 5. Exhibited signs or symptoms of hemolysis at start of current aHUS event (i.e., lactate
 dehydrogenase (LDH) ≥1.5 x Upper Limit of Normal [ULN] and hemoglobin ≤LLN),
 fragmented RBC with a negative Coombs test.

 6. Serum Creatinine level ≥97 percentile for age at screening (patients requiring
 dialysis for acute renal failure are also eligible).

 7. Patients with aHUS due to complement regulatory protein genetic abnormality or
 anti-complement factor antibody or those in whom known etiologies of hemolytic uremic
 syndrome (HUS) have been ruled out as confirmed in the Exclusion Criteria.

 8. Patients must have been vaccinated against N. meningitidis, pneumococcus and
 haemophilus (per the vaccine label) at least 14 days prior to study drug initiation or
 otherwise be protected by prophylactic antibiotics. Patients under age two years were
 to receive antibiotic prophylaxis throughout the treatment period.

 9. Female patients of childbearing potential (female patients who have achieved menarche)
 must have been practicing an effective, reliable and medically approved contraceptive
 regimen during the entire duration of the study, including the follow-up period. At
 the time of the last follow-up visit, patients must have agreed to continue to use
 adequate contraception methods for up to five months following discontinuation of
 eculizumab treatment.

 10. Able and willing to comply with study procedures

 Exclusion:

 Any of the following was regarded as a criterion for exclusion from the study:

 1. Known familial ADAMTS-13 deficiency (ADAMTS-13 <5%).

 2. Shiga toxin E.coli-related hemolytic uremic syndrome (STEC-HUS [known Shiga toxin +
 E.coli]).

 3. History of malignancy within five years of screening.

 4. Known human immunodeficiency virus (HIV) infection.

 5. Identified drug exposure-related HUS.

 6. Infection-related HUS.

 7. HUS related to bone marrow transplant (BMT).

 8. HUS related to vitamin B12 deficiency.

 9. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or
 syndrome.

 10. Plasma Therapy for >5 weeks prior to enrollment.

 11. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy
 for end-stage renal disease [ESRD]).

 12. Patients with a confirmed diagnosis of sepsis defined as positive blood cultures
 within seven days of the screening visit and not treated with antibiotics to which the
 organism is sensitive.

 13. 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.

 14. Pregnancy or lactation.

 15. History of meningococcal/pneumococcal/gonococcal disease.

 16. 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.

 17. Patients receiving chronic intravenous immunoglobulin (IVIg) within eight weeks unless
 for unrelated medical condition (e.g., Hypogammaglobinemia), or chronic Rituximab
 therapy within 12 weeks of the screening visit.

 18. Patients receiving other immunosuppressive therapies such as steroids, mTOR
 inhibitors, calcineurin inhibitors (e.g., cyclosporine or tacrolimus are excluded
 unless: [1] part of an established post-transplant anti-rejection regime, or [2]
 patient has confirmed anti-Complement Factor antibodies antibody requiring
 immunosuppressive therapy or [3] steroids are being used for a condition other than
 aHUS (example asthma).

 19. Participation in any other investigational drug trial or device trial, or procedures
 beginning four weeks prior to screening and throughout the entire trial

 20. Prior use of eculizumab, hypersensitivity to eculizumab, to murine proteins or to one
 of the excipients.