Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS
Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS
The purpose of this study is to determine whether eculizumab is safe and effective in the
 treatment of adolescent patients with plasma therapy-resistant Atypical Hemolytic-Uremic
 Syndrome (aHUS).
Inclusion Criteria:

 1. Male or female patients from 12 and up to 18 years weighing ≥ 40 kg who have been
 diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).

 2. Decrease in platelet count despite at least 4 plasma therapy (PT) treatments in the 1
 week immediately prior to screening.

 1. Screening platelet count , < 150 x10^9/L and at least 25% lower than the average
 remission platelet count or

 2. If remission counts not available, platelet count at onset of the current aHUS
 episode must be ≤75x10^9/L and platelet count at screening must be ≤ 100 x 10^9/L
 despite PT treatment administration of at least 4 PT treatments in the 1 week
 immediately prior to screening

 3. Known complement regulatory protein genetic abnormality

 4. Lactate dehydrogenase (LDH) level ≥ ULN unless the patient has been receiving plasma
 exchange and LDH at the onset of the current aHUS episode was at least the ULN. If LDH
 is normal at screening, other markers indicative of ongoing hemolysis such as
 haptoglobin, schistocytes should be evaluated and discussed with Sponsor

 5. Creatinine level ≥ ULN for age

 6. Female patients of childbearing potential must be practicing an effective, reliable
 and medically approved contraceptive regimen during the entire duration of the study,
 including the follow-up period and for up to 5 months following of eculizumab
 treatment discontinuation.

 7. Patient's parents/legal guardian must be willing and able to give written informed
 consent and patient must be willing to give written informed assent.

 8. Able and willing to comply with study procedures.

 Exclusion Criteria:

 1. TTP, (defined as ADAMTS-13 activity <5%) from an historical observation (prior to
 initiation of plasma therapy) or as tested at the screening visit by the central
 laboratory

 2. Malignancy within 5 years of screening.

 3. Typical HUS (Shiga toxin +).

 4. Known HIV infection.

 5. Identified drug exposure-related HUS.

 6. Infection-related HUS.

 7. HUS related to bone marrow transplant

 8. HUS related to vitamin B12 deficiency

 9. Renal function status requiring chronic dialysis

 10. Patients with a confirmed diagnosis of sepsis

 11. 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.

 12. Pregnancy or lactation.

 13. Unresolved meningococcal disease.

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

 15. 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.

 16. Patients who have received previous treatment with eculizumab

 17. Patients receiving IVIG within 8 weeks or Rituximab therapy within 12 weeks of
 screening.

 18. Patients receiving other immunosuppressive therapies such as steroids, mTOR inhibitors
 or tacrolimus are excluded unless: [1] part of an established 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 or [4] patient is experiencing an acute
 aHUS relapse immediately after transplant

 19. Patients receiving Erythrocyte Stimulating Agents (ESAs) unless already on a stable
 dose for at least 4 weeks prior to the screening period or a washout period of at
 least 2 weeks from the last dose of ESA therapy.

 20. 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.

 21. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients

 22. Patients between ages from 12 and up to 18 years weighing < 40 kg