Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS
- Registration Number
- NCT00844545
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
Not provided
- 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
- Malignancy within 5 years of screening
- Typical HUS (Shiga toxin +)
- Known HIV infection
- Identified drug exposure-related HUS.
- Infection-related HUS
- HUS related to bone marrow transplant
- HUS related to vitamin B12 deficiency
- Renal function status requiring chronic dialysis
- Patients with a confirmed diagnosis of sepsis
- 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
- Pregnancy or lactation
- Unresolved meningococcal disease
- Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome
- 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
- Patients who have received previous treatment with eculizumab
- Patients receiving IVIG within 8 weeks or Rituximab therapy within 12 weeks of screening.
- 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
- 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.
- 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.
- Hypersensitivity to eculizumab, to murine proteins or to one of the excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Eculizumab Eculizumab -
- Primary Outcome Measures
Name Time Method Platelet Count Change From Baseline to 26 Weeks From Baseline to 26 weeks Percentage of Patients With Platelet Count Normalization Through 26 weeks 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.
Percentage of Patients With Hematologic Normalization Through 26 weeks 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.
- Secondary Outcome Measures
Name Time Method Percentage of Patients With Hematologic Normalization Through End of Study, Median Exposure 100.29 Weeks 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.
Percentage of Patients With Complete TMA Response Through End of Study, Median Exposure 100.29 Weeks 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.
TMA Intervention Rate Through End of Study, Median Exposure 100.29 Weeks 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.
Platelet Count Change From Baseline to 156 Weeks From Baseline to 156 Weeks Percentage of Patients With Platelet Count Normalization Through End of Study, Median Exposure 100.29 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.
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.