Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS
Condition: Atypical Hemolytic Uremic Syndrome
MeSH terms: Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome; Syndrome; Hemolysis
Intervention: Eculizumab
Intervention description: All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.
Intervention MeSH terms: Eculizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: aHUS

Summary:

      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).
    

Eligibility criteria:

        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