Clinical Trial: Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (aHUS)

Brief 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).

Detailed Summary:
Sponsor: Alexion Pharmaceuticals

Current Primary Outcome:

• Platelet Count Change From Baseline to 26 Weeks [ Time Frame: From Baseline to 26 weeks ]
• Percentage of Patients With Platelet Count Normalization [ Time Frame: 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 [ Time Frame: 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.

Original Primary Outcome: Assess the effect of eculizumab to reduce thrombotic microangiopathy (TMA). [ Time Frame: Through 26 Weeks ]

Current Secondary Outcome:

• Percentage of Patients With Complete TMA Response [ Time Frame: Through 26 weeks ]
  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 ≥ 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 [ Time Frame: Through 26 weeks ]
  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.
• Platelet Count Change From Baseline to 156 Weeks [ Time Frame: From Baseline to 156 Weeks ]
• Percentage of Patients With Platelet Count Normalization [ Time Frame: 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.
• Percentage of Patients With Hematologic Normalization [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
• Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration [ Time Frame: Induction Phase for 4 weeks followed by Maintenance Phase starting on Week 5 through 26 weeks or longer ]

Original Secondary Outcome:

• Additional efficacy endpoints related to manifestations of TMA. [ Time Frame: Through 26 weeks ]
• Pharmacokinetics (PK) and pharmacodynamics (PD) of eculizumab in patients with aHUS. [ Time Frame: Through 26 Weeks ]
• Overall safety and tolerability of eculizumab. [ Time Frame: Through 26 Weeks ]

Dates:
Date Received: February 13, 2009
Date Started: May 2009
Date Completion:
Last Updated: June 30, 2015
Last Verified: June 2015