Atypical Hemolytic Uremic SyndromePhase 2aHUSNCT00844428
Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Sensitive aHUS
A Phase 2 study testing eculizumab in people with Atypical Hemolytic Uremic Syndrome, run by Alexion Pharmaceuticals, Inc. at 13 sites in 7 countries.
Trial summary
The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adolescent patients with plasma therapy-sensitive Atypical Hemolytic-Uremic Syndrome (aHUS). Read more about this study
- Who is it for?
- Ages 12 to 17 years
- 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
- 5 participants
- Where
- 13 sitesin 7 countries
- Study dates
- Jul 2009to Dec 2013
- 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 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female patients between ages from 12 and up to 18 years of age weighing ≥ 40 kg 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 the 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.
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- 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.
- Patient's parents/legal guardian must be willing and able to give written informed consent and patient must be willing to give written informed assent (if applicable as determined by the IRB/IEC).
- Able and willing to comply with study procedures.
Who cannot join
- 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.
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- 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 Obeservation 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.
- Patients between the ages from 12 and up to 18 years weighing < 40 kg.
Trial locations and contacts
13 sites in 7 countries.
13 sites in 7 countries
France6 sites
Study site
Bois-Guillaume, 76230
Study site
Bordeaux, 33076
Study site
Lyon, 69437
Study site
Nantes, 44093
Study site
Paris, 75743
Study site
Starsbourg, 67091
About this study
Official title: An Open-Label, Multi-Center Controlled Clinical Trial Of Eculizumab in Adolescent 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 adolescent patients with plasma therapy-sensitive Atypical Hemolytic-Uremic Syndrome (aHUS).
- Conditions
- Atypical Hemolytic Uremic Syndrome
- Being tested
- eculizumab
- 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 TMA Event-free Status
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.
Measured: Through 26 weeks
Percentage of Patients With Hematologic Normalization
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.
Measured: Through 26 weeks
Percentage of Patients With Complete TMA Response
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.
Measured: Through 26 weeks
Secondary outcomes (10)
TMA Intervention Rate
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.
Measured: Through 26 weeks
Platelet Count Change From Baseline to 26 Weeks
Measured: From Baseline to 26 Weeks
Percentage of Patients With Platelet Count Normalization
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
Measured: Through 26 Weeks
Percentage of Patients With TMA Event-free Status
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.
Measured: Through End of Study, Median Exposure 156 Weeks
Percentage of Patients With Hematologic Normalization
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.
Measured: Through End of Study, Median Exposure 156 Weeks
Percentage of Patients With Complete TMA Response
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.
Measured: Through End of Study, Median Exposure 156 Weeks
TMA Intervention Rate
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.
Measured: Through End of Study, Median Exposure 156 Weeks
Platelet Count Change From Baseline to 156 Weeks
Measured: From Baseline to 156 Weeks
Percentage of Patients With Platelet Count Normalization
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.
Measured: Through End of Study, Median Exposure 156 Weeks
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration
Measured: Induction Phase for 4 weeks followed by Maintenance Phase starting on Week 5 through 26 weeks or longer.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2009 (estimated)
- Study startJul 2009
- Primary completionOct 2010
- Study completionDec 2013
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
- 5 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
- NCT00844428
- Sponsor's protocol ID
- C08-003B
- Other IDs
- BB-IND 11075, EudraCT Number 2008-006955-28
- Acronym
- aHUS
- Status last verified
- Jun 2015
- First submitted
- 12 Feb 2009
- Last updated
- 23 Jul 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 33783815Legendre 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.
PubMed 23738544
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multi-Center Controlled Clinical Trial Of Eculizumab in Adolescent Patients With Plasma Therapy-Sensitive Atypical Hemolytic Uremic Syndrome (AHUS)
- ClinicalTrials.gov ID
- NCT00844428
- Acronym / sponsor ID
- aHUS / C08-003B
- Conditions
- Atypical Hemolytic Uremic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 16 Feb 2009 (estimated)
- Results
- Posted 26 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adolescent patients with plasma therapy-sensitive Atypical Hemolytic-Uremic Syndrome (aHUS).
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
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Male or female patients between ages from 12 and up to 18 years of age weighing ≥ 40 kg 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 the 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.
Key exclusion criteria (21 listed)
- 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.
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 TMA Event-free Status
Time frame: Through 26 weeks
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.
Percentage of Patients With Hematologic Normalization
Time frame: Through 26 weeks
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.
Percentage of Patients With Complete TMA Response
Time frame: Through 26 weeks
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.
10 secondary outcomes
TMA Intervention Rate
Time frame: Through 26 weeks
Platelet Count Change From Baseline to 26 Weeks
Time frame: From Baseline to 26 Weeks
Percentage of Patients With Platelet Count Normalization
Time frame: Through 26 Weeks
Percentage of Patients With TMA Event-free Status
Time frame: Through End of Study, Median Exposure 156 Weeks
Percentage of Patients With Hematologic Normalization
Time frame: Through End of Study, Median Exposure 156 Weeks
Percentage of Patients With Complete TMA Response
Time frame: Through End of Study, Median Exposure 156 Weeks
TMA Intervention Rate
Time frame: Through End of Study, Median Exposure 156 Weeks
Platelet Count Change From Baseline to 156 Weeks
Time frame: From Baseline to 156 Weeks
Percentage of Patients With Platelet Count Normalization
Time frame: Through End of Study, Median Exposure 156 Weeks
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 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 23738544Legendre 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.
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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.
13 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 13 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 9 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 23 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in France, United Kingdom, Canada, 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 26 Jan 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 TMA Event-free Status (time frame: Through 26 weeks). The study lists 3 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 NCT00844428, 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 23 Jul 2015.