Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS)

Phase 2

Completed

• Conditions: Atypical Hemolytic Uremic Syndrome
• Interventions: Drug: eculizumab

• Registration Number: NCT00838513
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

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-sensitive Atypical Hemolytic-Uremic Syndrome (aHUS).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-02-03
• Study First Submitted QC: 2009-02-04
• Study First Posted: 2009-02-06
• Study Start: 2009-07
• Primary Completion: 2010-10
• Study Completion: 2013-12
• Results First Submitted: 2014-12-15
• Results First Submitted QC: 2015-01-19
• Results First Posted: 2015-01-26
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-30
• Last Update Posted: 2015-07-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

1. 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.
2. Malignancy within 5 years of screening.
3. Typical HUS (Shiga toxin +).
4. Known HIV infection.
5. Identified drug exposure-related HUS.
6. Infection-related HUS.
7. HUS related to bone marrow transplant.
8. HUS related to vitamin B12 deficiency.
9. Patients with a confirmed diagnosis of sepsis.
10. 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.
11. Pregnancy or lactation.
12. Unresolved meningococcal disease.
13. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
14. 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.
15. Patients who have received previous treatment with eculizumab.
16. Patients receiving IVIg within 8 weeks or Rituximab therapy within 12 weeks of the screening visit.
17. 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.
18. 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.
19. 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.
20. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
eculizumab	eculizumab	-

Primary Outcome Measures

Name	Time	Method
Percentage of Patients With TMA Event-free Status	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	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	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.

Secondary Outcome Measures

Name	Time	Method
Platelet Count Change From Baseline to 26 Weeks	From Baseline to 26 Weeks
Percentage of Patients With Platelet Count Normalization	Through End of Study, Median Exposure 156 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 Not specified.
TMA Intervention Rate	Through End of Study, Median Exposure 156 Weeks	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.
Percentage of Patients With Complete TMA Response	Through End of Study, Median Exposure 156 Weeks	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.
Platelet Count Change From Baseline to 156 Weeks	From Baseline to 156 Weeks
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration	Induction Phase for 4 weeks followed by Maintenance Phase starting on Week 5 through 26 weeks or longer.
Percentage of Patients With TMA Event-free Status	Through End of Study, Median Exposure 156 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	Through End of Study, Median Exposure 156 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.