Atypical Hemolytic Uremic Syndrome Clinical Trial
— aHUSOfficial title:
An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (aHUS)
The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adult patients with plasma therapy-resistant Atypical Hemolytic-Uremic Syndrome (aHUS).
Status | Completed |
Enrollment | 16 |
Est. completion date | July 2013 |
Est. primary completion date | September 2010 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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 |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Alexion Pharmaceuticals |
United States, Austria, France, Germany, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Platelet Count Change From Baseline to 26 Weeks | From Baseline to 26 weeks | No | |
Primary | Percentage of Patients With Platelet Count Normalization | The primary objective of the study (per protocol) was to assess the effect of eculizumab to reduce TMA as measured by platelet count change from baseline (BL) during the Treatment Period (26 weeks) in patients with plasma therapy (PT)-resistant aHUS (protocol defined), including assessment of the proportion of patients who achieved Platelet Count Normalization from baseline through 26 weeks. Platelet Count Normalization was defined as the platelet count observed to be =150 x 10^9/L on at least two consecutive measurements which span a period of at least four weeks. | Through 26 weeks | No |
Primary | Percentage of Patients With Hematologic Normalization | Hematologic Normalization was defined as normalization of both platelet count and lactic dehydrogenase (LDH) sustained for at least two consecutive measurements which spanned a period of at least four weeks. | Through 26 weeks | No |
Secondary | Percentage of Patients With Complete TMA Response | The proportion of patients who achieved a Complete TMA Response from baseline through 26 weeks of treatment with eculizumab was determined. Complete TMA Response was defined as Hematologic Normalization plus improvement in renal function (defined as as =25% reduction from baseline in serum creatinine), which was sustained for two consecutive measurements over a period of at least four weeks. | Through 26 weeks | No |
Secondary | TMA Intervention Rate | TMA Intervention Rate (# PE/PI and # Dialysis Events/Patient/Day) in the eculizumab treatment period (from baseline through 26 weeks) for PE/PI and (from the fifteenth day following the first eculizumab dose through 26 weeks) for new dialysis events was compared with the TMA Intervention Rate during the pre-eculizumab treatment period. | Through 26 weeks | No |
Secondary | Platelet Count Change From Baseline to 156 Weeks | From Baseline to 156 Weeks | No | |
Secondary | Percentage of Patients With Platelet Count Normalization | Platelet Count Normalization was defined as the platelet count observed to be =150 x 10^9/L on at least two consecutive measurements which span a period of at least four weeks. | Through End of Study, Median Exposure 100.29 Weeks | No |
Secondary | Percentage of Patients With Hematologic Normalization | Hematologic Normalization was defined as normalization of both platelet count and lactic dehydrogenase (LDH) sustained for at least two consecutive measurements which spanned a period of at least four weeks. | Through End of Study, Median Exposure 100.29 Weeks | No |
Secondary | Percentage of Patients With Complete TMA Response | The proportion of patients who achieved a Complete TMA Response from baseline through end of the study was determined. Complete TMA Response was defined as Hematologic Normalization plus improvement in renal function (defined as =25% reduction from baseline in serum creatinine), which was sustained for two consecutive measurements over a period of at least four weeks. | Through End of Study, Median Exposure 100.29 Weeks | No |
Secondary | TMA Intervention Rate | TMA Intervention Rate (# PE/PI and # Dialysis Events/Patient/Day) in the eculizumab treatment period (from baseline through end of the study) for PE/PI and (from the fifteenth day following the first eculizumab dose through end of the study) for new dialysis events was compared with the TMA Intervention Rate during the pre-eculizumab treatment period. | Through End of Study, Median Exposure 100.29 Weeks | No |
Secondary | Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration | Induction Phase for 4 weeks followed by Maintenance Phase starting on Week 5 through 26 weeks or longer. | No |
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