An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
Condition: Atypical Hemolytic-Uremic Syndrome
MeSH terms: Azotemia; 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
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Atypical Hemolytic-Uremic Syndrome

Summary:

      The record Primary purpose is to assess the efficacy of eculizumab in adult patients with
      Atypical Hemolytic- Uremic Syndrome (aHUS) to control Thrombotic Microangiopathy (TMA) as
      characterized by thrombocytopenia, hemolysis and renal impairment.
    

Eligibility criteria:

        Inclusion:

          1. Patient must be willing and able to give written informed consent.

          2. Patient's age > 18 years.

          3. Patients exhibit thrombocytopenia, hemolysis and elevated Serum Creatinine.

          4. Patients with diagnosis of aHUS with or without an identified complement regulatory
             protein genetic abnormality or anti-complement factor antibody and for whom etiologies
             of hemolytic uremic syndrome have been ruled out as confirmed in the exclusion
             criteria

          5. 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. At the time of the last follow-up visit, patients must
             agree to continue to use adequate contraception methods for up to 5 months following
             discontinuation of eculizumab treatment.

          6. Able and willing to comply with study procedures

        Exclusion:

          1. Chronic dialysis.

          2. Prior eculizumab use or hypersensitivity to eculizumab, to murine proteins or to one
             of the excipients.

          3. Known familial a disintegrin and metalloproteinase with a thrombospondin type 1 motif,
             member 13 (ADAMTS-13) deficiency (ADAMTS-13 <5%).

          4. Typical Hemolytic-Uremic Syndrome (HUS) (known Shiga toxin +).

          5. History of malignancy within 5 years of screening.

          6. Known human immunodeficiency virus (HIV) infection.

          7. Identified drug exposure-related hemolytic-uremic syndrome (HUS).

          8. Infection-related HUS.

          9. HUS related to bone marrow transplant (BMT).

         10. HUS related to vitamin B12 deficiency.

         11. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or
             syndrome.

         12. Patients with a confirmed diagnosis of sepsis defined as positive blood cultures
             within 7 days of the screening visit and not treated with antibiotics to which the
             organism is sensitive.

         13. 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.

         14. Pregnancy or lactation.

         15. Unresolved systemic meningococcal disease.

         16. 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.

         17. Patients receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks or chronic
             Rituximab therapy within 12 weeks of screening visit.

         18. Patients receiving other immunosuppressive therapies such as steroids, mechanist
             target of rapamycin (mTOR) inhibitors, calcineurin inhibitors (e.g., cyclosporine or
             tacrolimus) are excluded unless: [1] part of an established post-transplant
             anti-rejection regime, or [2] patient has confirmed anti-Complement Factor Antibodies
             requiring immunosuppressive therapy, or [3] steroids are being used for a condition
             other than aHUS (example asthma).

         19. Participation in any other investigational drug trial or device trial, or procedures
             beginning 4 weeks prior to screening and throughout the entire trial.