Back to resultsOpen Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS (aHUS)
Primary Purpose
Atypical Hemolytic Uremic Syndrome
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Eculizumab
Sponsored by
About this trial
This is an interventional treatment trial for Atypical Hemolytic Uremic Syndrome focused on measuring aHUS
Eligibility Criteria
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
- Renal function status requiring chronic dialysis
- 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 screening.
- 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 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Eculizumab
Arm Description
Outcomes
Primary Outcome Measures
Platelet Count Change From Baseline to 26 Weeks
Percentage of Patients With Platelet Count Normalization
The primary objective of the study (per protocol) was to assess the effect of eculizumab to reduce TMA as measured by platelet count change from baseline (BL) during the Treatment Period (26 weeks) in patients with plasma therapy (PT)-resistant aHUS (protocol defined), including assessment of the proportion of patients who achieved Platelet Count Normalization from baseline through 26 weeks. 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.
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.
Secondary Outcome Measures
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 as ≥25% reduction from baseline in serum creatinine), which was sustained for two consecutive measurements over a period of at least four weeks.
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.
Platelet Count Change 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.
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.
Percentage of Patients With Complete TMA Response
The proportion of patients who achieved a Complete TMA Response from baseline through end of the study 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.
TMA Intervention Rate
TMA Intervention Rate (# PE/PI and # Dialysis Events/Patient/Day) in the eculizumab treatment period (from baseline through end of the study) for PE/PI and (from the fifteenth day following the first eculizumab dose through end of the study) for new dialysis events was compared with the TMA Intervention Rate during the pre-eculizumab treatment period.
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00844545
Brief Title
Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS
Acronym
aHUS
Official Title
An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (aHUS)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
July 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adult patients with plasma therapy-resistant Atypical Hemolytic-Uremic Syndrome (aHUS).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atypical Hemolytic Uremic Syndrome
Keywords
aHUS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Eculizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Eculizumab
Intervention Description
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
Primary Outcome Measure Information:
Title
Platelet Count Change From Baseline to 26 Weeks
Time Frame
From Baseline to 26 weeks
Title
Percentage of Patients With Platelet Count Normalization
Description
The primary objective of the study (per protocol) was to assess the effect of eculizumab to reduce TMA as measured by platelet count change from baseline (BL) during the Treatment Period (26 weeks) in patients with plasma therapy (PT)-resistant aHUS (protocol defined), including assessment of the proportion of patients who achieved Platelet Count Normalization from baseline through 26 weeks. 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.
Time Frame
Through 26 weeks
Title
Percentage of Patients With Hematologic Normalization
Description
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.
Time Frame
Through 26 weeks
Secondary Outcome Measure Information:
Title
Percentage of Patients With Complete TMA Response
Description
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 as ≥25% reduction from baseline in serum creatinine), which was sustained for two consecutive measurements over a period of at least four weeks.
Time Frame
Through 26 weeks
Title
TMA Intervention Rate
Description
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.
Time Frame
Through 26 weeks
Title
Platelet Count Change From Baseline to 156 Weeks
Time Frame
From Baseline to 156 Weeks
Title
Percentage of Patients With Platelet Count Normalization
Description
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.
Time Frame
Through End of Study, Median Exposure 100.29 Weeks
Title
Percentage of Patients With Hematologic Normalization
Description
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.
Time Frame
Through End of Study, Median Exposure 100.29 Weeks
Title
Percentage of Patients With Complete TMA Response
Description
The proportion of patients who achieved a Complete TMA Response from baseline through end of the study 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.
Time Frame
Through End of Study, Median Exposure 100.29 Weeks
Title
TMA Intervention Rate
Description
TMA Intervention Rate (# PE/PI and # Dialysis Events/Patient/Day) in the eculizumab treatment period (from baseline through end of the study) for PE/PI and (from the fifteenth day following the first eculizumab dose through end of the study) for new dialysis events was compared with the TMA Intervention Rate during the pre-eculizumab treatment period.
Time Frame
Through End of Study, Median Exposure 100.29 Weeks
Title
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Renal function status requiring chronic dialysis
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 screening.
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 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
Facility Information:
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
City
Grapevine
State/Province
Texas
ZIP/Postal Code
76051
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
City
Bordeaux
ZIP/Postal Code
33076
Country
France
City
Lyon
ZIP/Postal Code
69437
Country
France
City
Nantes
ZIP/Postal Code
44093
Country
France
City
Paris
ZIP/Postal Code
75743
Country
France
City
Quimper
ZIP/Postal Code
29107
Country
France
City
Saint Priest en Jarez
ZIP/Postal Code
42270
Country
France
City
Tours
ZIP/Postal Code
37044
Country
France
City
Aachen
ZIP/Postal Code
52074
Country
Germany
City
Essen
ZIP/Postal Code
45147
Country
Germany
City
Newcastle
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33783815
Citation
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.
Results Reference
derived
PubMed Identifier
23738544
Citation
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.
Results Reference
derived
Learn more about this trial
Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS
We'll reach out to this number within 24 hrs