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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01194973
First received: August 31, 2010
Last updated: April 7, 2015
Last verified: April 2015
  Purpose

The record Primary purpose is to assess the efficacy of eculizumab in adult patients with aHUS to control TMA as characterized by thrombocytopenia, hemolysis and renal impairment.


Condition Intervention Phase
Atypical Hemolytic-Uremic Syndrome
Drug: Eculizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome

Resource links provided by NLM:


Further study details as provided by Alexion Pharmaceuticals:

Primary Outcome Measures:
  • Proportion of Patients With Complete TMA Response [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients With Modified Complete TMA Response [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Proportion of Patients With Complete Hematologic Response [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients With Platelet Count Normalization [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    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

  • Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    Proportion of Patients with Estimated Glomerular Filtration Rate (eGFR) Improvement was determined and defined as an increase in eGFR by ≥ 15 mL/min/1.73m2 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 ] [ Designated as safety issue: No ]
  • Proportion of Patients With Complete TMA Response [ Time Frame: Through End of Study, Median Exposure 52 Weeks ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients With Modified Complete TMA Response [ Time Frame: Through End of Study, Median Exposure 52 Weeks ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients With Complete Hematologic Response [ Time Frame: Through End of Study, Median Exposure 52 Weeks ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients With Platelet Count Normalization [ Time Frame: Through End of Study, Median Exposure 52 Weeks ] [ Designated as safety issue: No ]
    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

  • Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement [ Time Frame: Through End of Study, Median Exposure 52 Weeks ] [ Designated as safety issue: No ]
    Proportion of Patients with Estimated Glomerular Filtration Rate (eGFR) Improvement was determined and defined as an increase in eGFR by ≥ 15 mL/min/1.73m2 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 ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: July 2010
Study Completion Date: February 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eculizumab 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ADAMTS-13 deficiency (ADAMTS-13 <5%).
  4. Typical 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 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, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194973

Locations
United States, Massachusetts
Burlington, Massachusetts, United States, 01805
United States, New Jersey
Hackensack, New Jersey, United States, 07601
United States, New York
New York, New York, United States, 10032
United States, Ohio
Columbus, Ohio, United States, 43210
United States, Texas
Houston, Texas, United States, 77030
Belgium
Liège, Belgium, 4020
France
Caen, France, 14033
Lille, France, 59037
Nantes, France, 44093
Nice, France, 6000
Paris, France, 75743
Paris, France, 75970
Toulouse, France, 31059
Tours, France, 37044
Germany
Essen, Germany, 45147
Hannover, Germany, 30625
Italy
Bergamo, Italy, 24127
Firenze, Italy, 50134
Spain
Barcelona, Spain, 14004
Cordoba, Spain, 14004
United Kingdom
Exeter, United Kingdom
London, United Kingdom
Newcastle, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
  More Information

No publications provided

Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01194973     History of Changes
Other Study ID Numbers: C10-004
Study First Received: August 31, 2010
Results First Received: April 7, 2015
Last Updated: April 7, 2015
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Keywords provided by Alexion Pharmaceuticals:
Atypical Hemolytic-Uremic Syndrome

Additional relevant MeSH terms:
Hemolytic-Uremic Syndrome
Azotemia
Hemolysis
Syndrome
Anemia
Anemia, Hemolytic
Blood Platelet Disorders
Disease
Hematologic Diseases
Kidney Diseases
Pathologic Processes
Thrombocytopenia
Thrombotic Microangiopathies
Uremia
Urologic Diseases

ClinicalTrials.gov processed this record on May 25, 2015