Atypical Hemolytic-Uremic SyndromePhase 2aHUSNCT01193348
An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric 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 17 sites in 9 countries.
Trial summary
The primary purpose is to assess the efficacy and safety of eculizumab in pediatric patients with aHUS to control TMA as characterized by thrombocytopenia, hemolysis and renal impairment. Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Atypical Hemolytic-Uremic Syndrome
- What is being tested?
- Eculizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 17 sitesin 9 countries
- Study dates
- Sep 2010to Apr 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 1 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient's parent/legal guardian must have been willing and able to give written informed consent and the patient must have been willing to give written informed assent (if applicable as determined by the central IRB/IEC).
- Pediatric patients with aHUS: Patients could have been newly diagnosed, or with previously diagnosed disease, or post-kidney transplant with the disease.
- Patients one month to 18 years and body weight ≥ 5kg.
- Platelet count at screening and baseline visit must have been below lower limit of normal (<LLN). If screening visit and baseline visit are combined into one day, an additional platelet count value obtained at least 24 hours before screening/baseline sample must also be <LLN.
- Exhibited signs or symptoms of hemolysis at start of current aHUS event (i.e., lactate dehydrogenase (LDH) ≥1.5 x Upper Limit of Normal [ULN] and hemoglobin ≤LLN), fragmented RBC with a negative Coombs test.
- Serum Creatinine level ≥97 percentile for age at screening (patients requiring dialysis for acute renal failure are also eligible).
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- Patients with aHUS due to complement regulatory protein genetic abnormality or anti-complement factor antibody or those in whom known etiologies of hemolytic uremic syndrome (HUS) have been ruled out as confirmed in the Exclusion Criteria.
- Patients must have been vaccinated against N. meningitidis, pneumococcus and haemophilus (per the vaccine label) at least 14 days prior to study drug initiation or otherwise be protected by prophylactic antibiotics. Patients under age two years were to receive antibiotic prophylaxis throughout the treatment period.
- Female patients of childbearing potential (female patients who have achieved menarche) must have been 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 have agreed to continue to use adequate contraception methods for up to five months following discontinuation of eculizumab treatment.
- Able and willing to comply with study procedures
Who cannot join
- Any of the following was regarded as a criterion for exclusion from the study:
- Known familial ADAMTS-13 deficiency (ADAMTS-13 <5%).
- Shiga toxin E.coli-related hemolytic uremic syndrome (STEC-HUS [known Shiga toxin + E.coli]).
- History of malignancy within five years of screening.
- Known human immunodeficiency virus (HIV) infection.
- Identified drug exposure-related HUS.
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- 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.
- Plasma Therapy for >5 weeks prior to enrollment.
- Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage renal disease [ESRD]).
- Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within seven 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.
- History of meningococcal/pneumococcal/gonococcal 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 eight weeks unless for unrelated medical condition (e.g., Hypogammaglobinemia), or chronic Rituximab therapy within 12 weeks of the screening visit.
- 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 antibody 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 four weeks prior to screening and throughout the entire trial
- Prior use of eculizumab, hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
Trial locations and contacts
17 sites in 9 countries.
17 sites in 9 countries
United States4 sites
Study site
Atlanta, Georgia, 30322
Study site
Corpus Christi, Texas, 78411
Study site
Hackensack, New Jersey, 07601
Study site
Spokane, Washington, 99204
France4 sites
Study site
Lille, 59800
Study site
Marseille, 13385
Study site
Paris, 75935
Study site
Rouen, 76000
About this study
The primary purpose is to assess the efficacy and safety of eculizumab in pediatric patients with aHUS to control 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
Fixed dosing is based on body weight cohorts. Adjustment of dose to accommodate patient growth is possible.
| 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.
Proportion 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 ≥ 25% improvement in serum creatinine from baseline which was sustained for at least two consecutive measurements obtained at least four weeks apart).
Measured: Through 26 weeks
Secondary outcomes (14)
Proportion of Patients With Complete Hematologic Response
Proportion of Patients with Complete Hematologic response through 26 weeks 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 26 weeks
Proportion 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
Proportion 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/1.73m2 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
Proportion 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 ≥ 25% improvement in serum creatinine from baseline which was sustained for at least two consecutive measurements obtained at least four weeks apart).
Measured: Through End of Study, Median Exposure 55 Weeks
Proportion 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 End of Study, Median Exposure 55 Weeks
Proportion of Patients With Platelet Count Normalization
Proportion of Patients with Platelet Count Normalization through end of study 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 55 Weeks
Proportion 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/1.73m2 from baseline, sustained for at least two consecutive measurements obtained at least four weeks apart.
Measured: Through End of Study, Median Exposure 55 Weeks
Platelet Count Change From Baseline to 52 Weeks
Measured: Through 52 Weeks
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 5 - <10kg) N=3
Measured: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort.Maintenance Phase was started 1 week after induction phase and dosing of eculizumab administration was every 2 weeks or every 3 weeks depending on patient weight cohort
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 10 - <20kg) N=7
Measured: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort.Maintenance Phase was started 1 week after induction phase and dosing of eculizumab administration was every 2 weeks or every 3 weeks depending on patient weight cohort
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 20 - <30kg)
Measured: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 30 - <40kg) N=1
Measured: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort ≥40kg) N=5
Measured: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionJan 2014
- Study completionApr 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 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
- NCT01193348
- Sponsor's protocol ID
- C10-003
- Acronym
- aHUS
- Status last verified
- Apr 2015
- First submitted
- 31 Aug 2010
- Last updated
- 29 Apr 2015
- 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 33783815Tschumi S, Gugger M, Bucher BS, Riedl M, Simonetti GD. Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatr Nephrol. 2011 Nov;26(11):2085-8. doi: 10.1007/s00467-011-1989-4. Epub 2011 Aug 30.
PubMed 21877169
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2015. 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 Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
- ClinicalTrials.gov ID
- NCT01193348
- Acronym / sponsor ID
- aHUS / C10-003
- Conditions
- Atypical Hemolytic-Uremic Syndrome
- Keywords
- Atypical Hemolytic-Uremic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Jan 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 1 Sep 2010 (estimated)
- Results
- Posted 29 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 primary purpose is to assess the efficacy and safety of eculizumab in pediatric patients with aHUS to control TMA as characterized by thrombocytopenia, hemolysis and renal impairment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: Eculizumab |
Who may qualify
- Ages
- 1 month to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Patient's parent/legal guardian must have been willing and able to give written informed consent and the patient must have been willing to give written informed assent (if applicable as determined by the central IRB/IEC).
- Pediatric patients with aHUS: Patients could have been newly diagnosed, or with previously diagnosed disease, or post-kidney transplant with the disease.
- Patients one month to 18 years and body weight ≥ 5kg.
- Platelet count at screening and baseline visit must have been below lower limit of normal (<LLN). If screening visit and baseline visit are combined into one day, an additional platelet count value obtained at least 24 hours before screening/baseline sample must also be <LLN.
- Exhibited signs or symptoms of hemolysis at start of current aHUS event (i.e., lactate dehydrogenase (LDH) ≥1.5 x Upper Limit of Normal [ULN] and hemoglobin ≤LLN), fragmented RBC with a negative Coombs test.
Key exclusion criteria (21 listed)
- Known familial ADAMTS-13 deficiency (ADAMTS-13 <5%).
- Shiga toxin E.coli-related hemolytic uremic syndrome (STEC-HUS [known Shiga toxin + E.coli]).
- History of malignancy within five years of screening.
- Known human immunodeficiency virus (HIV) infection.
- Identified drug exposure-related HUS.
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 |
|---|---|---|
| EculizumabFixed dosing is based on body weight cohorts. Adjustment of dose to accommodate patient growth is possible. | Drug | Eculizumab |
Primary outcome
Proportion 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 ≥ 25% improvement in serum creatinine from baseline which was sustained for at least two consecutive measurements obtained at least four weeks apart).
14 secondary outcomes
Proportion of Patients With Complete Hematologic Response
Time frame: Through 26 weeks
Proportion of Patients With Platelet Count Normalization
Time frame: Through 26 weeks
Proportion 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
Proportion of Patients With Complete TMA Response
Time frame: Through End of Study, Median Exposure 55 Weeks
Proportion of Patients With Complete Hematologic Response
Time frame: Through End of Study, Median Exposure 55 Weeks
Proportion of Patients With Platelet Count Normalization
Time frame: Through End of Study, Median Exposure 55 Weeks
Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
Time frame: Through End of Study, Median Exposure 55 Weeks
Platelet Count Change From Baseline to 52 Weeks
Time frame: Through 52 Weeks
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 5 - <10kg) N=3
Time frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort.Maintenance Phase was started 1 week after induction phase and dosing of eculizumab administration was every 2 weeks or every 3 weeks depending on patient weight cohort
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 10 - <20kg) N=7
Time frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort.Maintenance Phase was started 1 week after induction phase and dosing of eculizumab administration was every 2 weeks or every 3 weeks depending on patient weight cohort
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 20 - <30kg)
Time frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 30 - <40kg) N=1
Time frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort ≥40kg) N=5
Time frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2015.
- 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 21877169Tschumi S, Gugger M, Bucher BS, Riedl M, Simonetti GD. Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatr Nephrol. 2011 Nov;26(11):2085-8. doi: 10.1007/s00467-011-1989-4. Epub 2011 Aug 30.
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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.
17 sites in 9 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 17 sites in 9 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 10 inclusion and 21 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 29 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, France, Italy, United Kingdom, Australia and 4 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 29 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?
Proportion of Patients With Complete TMA Response (time frame: Through 26 weeks). 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 NCT01193348, 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 29 Apr 2015.