open label controlled trial of eculizumab in adolescent patients with plasma therapy-sensitive ahus

Conditions: Atypical Hemolytic Uremic Syndrome

Summary: the purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adolescent patients with plasma therapy-sensitive atypical hemolytic-uremic syndrome (ahus).


Eligibility criteria:
inclusion criteria: 1. male or female patients between ages from 12 and up to 18 years of age weighing ≥ 40 kg who have been diagnosed with atypical hemolytic-uremic syndrome (ahus). 2. patients must be receiving pt for ahus and must be observed to receive ≥ 1 pt treatment every two weeks and no more than 3 pt treatments/week (at an unchanged frequency) for at least 8 weeks before the first dose of ip. 3. platelet count pre-pt baseline set-point (collected in the hours before the qualifying pt episode) is within 75% of the average of the pre-pt platelet counts collected at screening and during the observation period. 4. known complement regulatory protein genetic abnormality. 5. lactate dehydrogenase (ldh) level at screening or at the onset of the current ahus episode was ≥ uln. if ldh is normal at screening, other markers indicative of ongoing hemolysis such as haptoglobin, schistocytes should be evaluated and discussed with sponsor. 6. creatinine level ≥ uln for age. 7. 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 eculizumab treatment discontinuation. 8. 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 (if applicable as determined by the irb/iec). 9. 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. patients with a confirmed diagnosis of sepsis. 10. 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. 11. pregnancy or lactation. 12. unresolved meningococcal disease. 13. known systemic lupus erythematosus (sle) or antiphospholipid antibody positivity or syndrome. 14. 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. 15. patients who have received previous treatment with eculizumab. 16. patients receiving ivig within 8 weeks or rituximab therapy within 12 weeks of the screening visit. 17. 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 and throughout the obeservation period or \[4\] patient is experiencing an acute ahus relapse immediately after transplant. 18. 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. 19. 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. 20. hypersensitivity to eculizumab, to murine proteins, or to one of the excipients. 21. patients between the ages from 12 and up to 18 years weighing \< 40 kg.