Table 5.

Criteria for assessment of the efficacy of eculizumab in adolescents with plasma therapy-resistant aHUS (NCT00844844)

Inclusion criteria

1. Male or female patients up to 18 years of age who have been diagnosed with atypical hemolytic uremic syndrome (aHUS)

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

Screening platelet count, 150 × 109/l and at least 25% lower than remission platelet count or

if remission counts not available, screening platelet count <75 × 109/l

3. Diagnosis of aHUS

4. Lactate dehydrogenase (LDH) level ≥ULN

5. Creatinine level ≥ULN for age

6. Female patients 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

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. ADAMTS13 inhibitor or deficiency (i.e. ADAMTS13 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

8. 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

9. Pregnancy or lactation

10. Unresolved meningococcal disease

11. Known systemic lupus erythematosus (SLE) or antiphospholipid antibody positivity or syndrome

12. 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

13. Patients receiving IVIG or rituximab therapy

14. 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

15. Patients receiving erythrocyte stimulating agents (ESAs) unless already on a stable dose for at least 4 weeks prior to the screening period

16. 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