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An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome

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ClinicalTrials.gov Identifier: NCT01194973
Recruitment Status : Completed
First Posted : September 3, 2010
Results First Posted : April 24, 2015
Last Update Posted : May 30, 2017
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE August 31, 2010
First Posted Date  ICMJE September 3, 2010
Results First Submitted Date  ICMJE April 7, 2015
Results First Posted Date  ICMJE April 24, 2015
Last Update Posted Date May 30, 2017
Study Start Date  ICMJE July 2010
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
  • Percentage of Patients With Complete TMA Response [ Time Frame: Through 26 weeks ]
    Proportion of Patients with Complete TMA response was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as < 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.
  • Percentage of Patients With Modified Complete TMA Response [ Time Frame: Through 26 weeks ]
    Proportion of Patients with Modified Complete TMA response through 26 weeks of treatment was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as ≥ 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.
Original Primary Outcome Measures  ICMJE
 (submitted: September 2, 2010)
Proportion of patients with complete TMA response. [ Time Frame: includes 26 weeks for the primary endpoint analysis with a possibility of continued treatment if patient continues to benefit from treatment for up to 2 years or until marketing approval for this indication. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
  • Percentage of Patients With Complete Hematologic Response [ Time Frame: Through 26 weeks ]
    Proportion of Patients with Complete Hematologic response through end of study was determined and defined by normalization of platelet count and LDH sustained for at least two consecutive measurements obtained at least four weeks apart.
  • Percentage of Patients With Platelet Count Normalization [ Time Frame: Through 26 weeks ]
    Proportion of Patients with Platelet Count Normalization through 26 weeks of treatment was determined and defined as the platelet count observed to be ≥ 150 x 109/L on at least two consecutive measurements which span a period of at least four weeks
  • Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement [ Time Frame: Through 26 weeks ]
    Proportion of Patients with Estimated Glomerular Filtration Rate (eGFR) Improvement was determined and defined as an increase in eGFR by ≥ 15 mL/min/1.73m^2 from baseline, sustained for at least two consecutive measurements obtained at least four weeks apart.
  • Platelet Count Change From Baseline to 26 Weeks [ Time Frame: Through 26 weeks ]
  • Percentage of Patients With Complete TMA Response [ Time Frame: Through End of Study, Median Exposure 52 Weeks ]
    Proportion of Patients with Complete TMA response through end of study was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as < 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.
  • Percentage of Patients With Modified Complete TMA Response [ Time Frame: Through End of Study, Median Exposure 52 Weeks ]
    Proportion of Patients with Modified Complete TMA response through end of study was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as ≥ 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.
  • Percentage of Patients With Complete Hematologic Response [ Time Frame: Through End of Study, Median Exposure 52 Weeks ]
    Proportion of Patients with Complete Hematologic response through end of study of treatment was determined and defined by normalization of platelet count and LDH sustained for at least two consecutive measurements obtained at least four weeks apart.
  • Percentage of Patients With Platelet Count Normalization [ Time Frame: Through End of Study, Median Exposure 52 Weeks ]
    Proportion of Patients with Platelet Count Normalization through end of study of treatment was determined and defined as the platelet count observed to be ≥ 150 x 109/L on at least two consecutive measurements which span a period of at least four weeks
  • Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement [ Time Frame: Through End of Study, Median Exposure 52 Weeks ]
    Proportion of Patients with Estimated Glomerular Filtration Rate (eGFR) Improvement was determined and defined as an increase in eGFR by ≥ 15 mL/min/1.73m^2 from baseline sustained for at least two consecutive measurements obtained at least four weeks apart
  • Platelet Count Change From Baseline to 52 Weeks [ Time Frame: Through 52 Weeks ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
Official Title  ICMJE An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Atypical Hemolytic-Uremic Syndrome
Intervention  ICMJE Drug: Eculizumab
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.
Study Arms  ICMJE Experimental: Eculizumab
Intervention: Drug: Eculizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 20, 2017)
44
Original Estimated Enrollment  ICMJE
 (submitted: September 2, 2010)
30
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01194973
Other Study ID Numbers  ICMJE C10-004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alexion Pharmaceuticals
Study Sponsor  ICMJE Alexion Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Alexion Pharmaceuticals
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP