Atypical Hemolytic-Uremic SyndromePhase 2NCT01194973
An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
A Phase 2 study testing Eculizumab in people with Atypical Hemolytic-Uremic Syndrome, run by Alexion Pharmaceuticals, Inc. at 23 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atypical Hemolytic-Uremic Syndrome
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 23 sitesin 7 countries
- Study dates
- Jul 2010to Feb 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must be willing and able to give written informed consent.
- Patient's age > 18 years.
- Patients exhibit thrombocytopenia, hemolysis and elevated Serum Creatinine.
- 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
- 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.
- Able and willing to comply with study procedures
Who cannot join
- Chronic dialysis.
- Prior eculizumab use or hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
- Known familial a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) deficiency (ADAMTS-13 <5%).
- Typical Hemolytic-Uremic Syndrome (HUS) (known Shiga toxin +).
- History of malignancy within 5 years of screening.
- Known human immunodeficiency virus (HIV) infection.
Show all 19Show fewer
- Identified drug exposure-related hemolytic-uremic syndrome (HUS).
- Infection-related HUS.
- HUS related to bone marrow transplant (BMT).
- HUS related to vitamin B12 deficiency.
- Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
- 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.
- 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 systemic meningococcal disease.
- 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 receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks or chronic Rituximab therapy within 12 weeks of screening visit.
- 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).
- Participation in any other investigational drug trial or device trial, or procedures beginning 4 weeks prior to screening and throughout the entire trial.
Trial locations and contacts
23 sites in 7 countries.
23 sites in 7 countries
France8 sites
Study site
Caen, 14033
Study site
Lille, 59037
Study site
Nantes, 44093
Study site
Nice, 6000
Study site
Paris, 75743
Study site
Paris, 75970
Study site
Toulouse, 31059
Study site
Tours, 37044
United States5 sites
Study site
Burlington, Massachusetts, 01805
Study site
Columbus, Ohio, 43210
Study site
Hackensack, New Jersey, 07601
Study site
Houston, Texas, 77030
Study site
New York, New York, 10032
United Kingdom3 sites
Study site
Exeter
Study site
London
Study site
Newcastle
About this study
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.
- Conditions
- Atypical Hemolytic-Uremic Syndrome
- Being tested
- Eculizumab
- Keywords
- Atypical Hemolytic-Uremic Syndrome
- Medical subject headings
- Atypical Hemolytic Uremic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
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 group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | Not described Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With Complete TMA Response
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.
Measured: Through 26 weeks
Percentage of Patients With Modified Complete TMA Response
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.
Measured: Through 26 weeks
Secondary outcomes (10)
Percentage of Patients With Complete Hematologic Response
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.
Measured: Through 26 weeks
Percentage of Patients With Platelet Count Normalization
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
Measured: Through 26 weeks
Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
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.
Measured: Through 26 weeks
Platelet Count Change From Baseline to 26 Weeks
Measured: Through 26 weeks
Percentage of Patients With Complete TMA Response
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.
Measured: Through End of Study, Median Exposure 52 Weeks
Percentage of Patients With Modified Complete TMA Response
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.
Measured: Through End of Study, Median Exposure 52 Weeks
Percentage of Patients With Complete Hematologic Response
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.
Measured: Through End of Study, Median Exposure 52 Weeks
Percentage of Patients With Platelet Count Normalization
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
Measured: Through End of Study, Median Exposure 52 Weeks
Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
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
Measured: Through End of Study, Median Exposure 52 Weeks
Platelet Count Change From Baseline to 52 Weeks
Measured: Through 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2010 (estimated)
- Study startJul 2010
- Primary completionOct 2013
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atypical Hemolytic-Uremic SyndromeStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01194973
- Sponsor's protocol ID
- C10-004
- Status last verified
- Apr 2015
- First submitted
- 31 Aug 2010
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 33783815Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, Bedrosian CL, Faas SJ. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015 May 21;125(21):3253-62. doi: 10.1182/blood-2014-09-600411. Epub 2015 Apr 1.
PubMed 25833956
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
- ClinicalTrials.gov ID
- NCT01194973
- Acronym / sponsor ID
- C10-004
- Conditions
- Atypical Hemolytic-Uremic Syndrome
- Keywords
- Atypical Hemolytic-Uremic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2010
- Primary completion
- Oct 2013 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 3 Sep 2010 (estimated)
- Results
- Posted 24 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: Eculizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient must be willing and able to give written informed consent.
- Patient's age > 18 years.
- Patients exhibit thrombocytopenia, hemolysis and elevated Serum Creatinine.
- 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
- 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.
Key exclusion criteria (19 listed)
- Chronic dialysis.
- Prior eculizumab use or hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
- Known familial a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) deficiency (ADAMTS-13 <5%).
- Typical Hemolytic-Uremic Syndrome (HUS) (known Shiga toxin +).
- History of malignancy within 5 years of screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EculizumabAll 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. | Drug | Eculizumab |
Primary outcome
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.
10 secondary outcomes
Percentage of Patients With Complete Hematologic Response
Time frame: Through 26 weeks
Percentage of Patients With Platelet Count Normalization
Time frame: Through 26 weeks
Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
Time frame: Through 26 weeks
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
Percentage of Patients With Modified Complete TMA Response
Time frame: Through End of Study, Median Exposure 52 Weeks
Percentage of Patients With Complete Hematologic Response
Time frame: Through End of Study, Median Exposure 52 Weeks
Percentage of Patients With Platelet Count Normalization
Time frame: Through End of Study, Median Exposure 52 Weeks
Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
Time frame: Through End of Study, Median Exposure 52 Weeks
Platelet Count Change From Baseline to 52 Weeks
Time frame: Through 52 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33783815Pugh 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.
- Derived from this study: PubMed 25833956Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, Bedrosian CL, Faas SJ. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015 May 21;125(21):3253-62. doi: 10.1182/blood-2014-09-600411. Epub 2015 Apr 1.
Related trials for Atypical Hemolytic-Uremic Syndrome
Active, not recruitingPhase 3
A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical Hemolytic Uremic Syndrome
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Active, not recruitingObservational study
A Prospective, Non-interventional, Observational Study of Presentation, Treatment Patterns and Outcomes in Atypical Hemolytic Uremic Syndrome Patients
Atypical Hemolytic Uremic Syndrome(aHUS)
Active, not recruitingPhase 3
A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical Hemolytic Uremic Syndrome
RecruitingObservational study
Ravulizumab Outcomes in Polish Patients With aHUS
Atypical Hemolytic Uremic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
23 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eculizumab in people with Atypical Hemolytic-Uremic Syndrome, run by Alexion Pharmaceuticals, Inc. at 23 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in France, United States, United Kingdom, Germany, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With Complete TMA Response (time frame: Through 26 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01194973, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2017.