- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00838513
Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS) (aHUS)
June 30, 2015 updated by: Alexion Pharmaceuticals
An Open-label, Multi-center Controlled Clinical Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive 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-sensitive Atypical Hemolytic-Uremic Syndrome (aHUS).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Toronto, Canada
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Bois-Guillaume, France, 76230
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Bordeaux, France, 33076
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Lyon, France, 69437
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Nantes, France, 44093
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Paris, France, 75743
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Strasbourg, France, 67091
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Hannover, Germany, 30625
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Genova, Italy, 16147
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Nijmegen, Netherlands, 6525
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Stockholm, Sweden, 14186
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Exeter, United Kingdom
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Glasgow, United Kingdom
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Critera:
- Male or female patients' ≥18 years of age who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).
- Patients must be receiving PT for aHUS and must be observed to receive ≥ 1 PT treatment every two weeks and no more than 3 PT treatments/week (at an unchanged frequency) for at least 8 weeks before first dose of IP.
- Platelet Count Pre-PT Baseline Set-Point (collected in the hours before the Qualifying PT Episode) is within 75% of the average of the Pre-PT platelet counts collected at Screening and during the Observation Period.
- Known complement regulatory protein genetic abnormality.
- Lactate dehydrogenase (LDH) level at screening or at the onset of the current aHUS episode was ≥ ULN. If LDH is normal at screening, other markers indicative of ongoing hemolysis such as haptoglobin, schistocytes should be evaluated and discussed with Sponsor.
- Creatinine level ≥ ULN for age.
- 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 and for up to 5 months following eculizumab treatment discontinuation.
- Able to give written informed consent.
- Able and willing to comply with study procedures.
Exclusion Criteria:
- 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.
- 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 the screening visit.
- 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 and throughout the Observation 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: eculizumab
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Patients With TMA Event-free Status
Time Frame: Through 26 weeks
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TMA Event-free status is defined as the absence for at least 12 weeks of [1] decrease in platelet count of > 25% from the Platelet Count Pre-PT Baseline Set Point; [2] PT while the patient is receiving eculizumab, and [3] new dialysis.
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Through 26 weeks
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Percentage of Patients With Hematologic Normalization
Time Frame: Through 26 weeks
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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.
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Through 26 weeks
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Percentage of Patients With Complete TMA Response
Time Frame: Through 26 weeks
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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.
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Through 26 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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TMA Intervention Rate
Time Frame: Through 26 weeks
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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.
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Through 26 weeks
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Platelet Count Change From Baseline to 26 Weeks
Time Frame: From Baseline to 26 Weeks
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From Baseline to 26 Weeks
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Percentage of Patients With Platelet Count Normalization
Time Frame: Through 26 Weeks
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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
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Through 26 Weeks
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Percentage of Patients With TMA Event-free Status
Time Frame: Through End of Study, Median Exposure 156 Weeks
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TMA Event-free status is defined as the absence for at least 12 weeks of [1] decrease in platelet count of > 25% from the Platelet Count Pre-PT Baseline Set Point; [2] PT while the patient is receiving eculizumab, and [3] new dialysis.
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Through End of Study, Median Exposure 156 Weeks
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Percentage of Patients With Hematologic Normalization
Time Frame: Through End of Study, Median Exposure 156 Weeks
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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.
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Through End of Study, Median Exposure 156 Weeks
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Percentage of Patients With Complete TMA Response
Time Frame: Through End of Study, Median Exposure 156 Weeks
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The proportion of patients who achieved a Complete TMA Response from baseline through end of study 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.
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Through End of Study, Median Exposure 156 Weeks
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TMA Intervention Rate
Time Frame: Through End of Study, Median Exposure 156 Weeks
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TMA Intervention Rate (# PE/PI and # Dialysis Events/Patient/Day) in the eculizumab treatment period (from baseline through end of study) for PE/PI and (from the fifteenth day following the first eculizumab dose through end of study) for new dialysis events was compared with the TMA Intervention Rate during the pre-eculizumab treatment period.
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Through End of Study, Median Exposure 156 Weeks
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Platelet Count Change From Baseline to 156 Weeks
Time Frame: From Baseline to 156 Weeks
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From Baseline to 156 Weeks
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Percentage of Patients With Platelet Count Normalization
Time Frame: Through End of Study, Median Exposure 156 Weeks
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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 Not specified.
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Through End of Study, Median Exposure 156 Weeks
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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.
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Induction Phase for 4 weeks followed by Maintenance Phase starting on Week 5 through 26 weeks or longer.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Pugh D, O'Sullivan ED, Duthie FA, Masson P, Kavanagh D. Interventions for atypical haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Mar 23;3(3):CD012862. doi: 10.1002/14651858.CD012862.pub2.
- Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nurnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. doi: 10.1056/NEJMoa1208981.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2009
Primary Completion (ACTUAL)
October 1, 2010
Study Completion (ACTUAL)
December 1, 2013
Study Registration Dates
First Submitted
February 3, 2009
First Submitted That Met QC Criteria
February 4, 2009
First Posted (ESTIMATE)
February 6, 2009
Study Record Updates
Last Update Posted (ESTIMATE)
July 23, 2015
Last Update Submitted That Met QC Criteria
June 30, 2015
Last Verified
June 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Kidney Diseases
- Urologic Diseases
- Disease
- Hematologic Diseases
- Anemia
- Thrombocytopenia
- Blood Platelet Disorders
- Anemia, Hemolytic
- Thrombotic Microangiopathies
- Uremia
- Syndrome
- Azotemia
- Hemolysis
- Hemolytic-Uremic Syndrome
- Atypical Hemolytic Uremic Syndrome
- Physiological Effects of Drugs
- Immunosuppressive Agents
- Immunologic Factors
- Complement Inactivating Agents
- Eculizumab
Other Study ID Numbers
- C08-003A
- BB-IND 11075
- EudraCT Number 2008-006954-17
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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