Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Sensitive 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: 5.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No

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.