Clinical trial NCT01194973: An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
Official title: An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atypical Hemolytic-Uremic Syndrome
Keywords: Atypical Hemolytic-Uremic Syndrome
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-09-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion:

1. Patient must be willing and able to give written informed consent.
2. Patient's age \> 18 years.
3. Patients exhibit thrombocytopenia, hemolysis and elevated Serum Creatinine.
4. 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
5. 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.
6. Able and willing to comply with study procedures

Exclusion:

1. Chronic dialysis.
2. Prior eculizumab use or hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
3. Known familial a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) deficiency (ADAMTS-13 \<5%).
4. Typical Hemolytic-Uremic Syndrome (HUS) (known Shiga toxin +).
5. History of malignancy within 5 years of screening.
6. Known human immunodeficiency virus (HIV) infection.
7. Identified drug exposure-related hemolytic-uremic syndrome (HUS).
8. Infection-related HUS.
9. HUS related to bone marrow transplant (BMT).
10. HUS related to vitamin B12 deficiency.
11. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
12. 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.
13. 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.
14. Pregnancy or lactation.
15. Unresolved systemic meningococcal disease.
16. 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.
17. Patients receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks or chronic Rituximab therapy within 12 weeks of screening visit.
18. 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).
19. Participation in any other investigational drug trial or device trial, or procedures beginning 4 weeks prior to screening and throughout the entire trial.

Primary outcomes:
measure: Percentage of Patients With Complete TMA Response
timeFrame: Through 26 weeks
measure: Percentage of Patients With Modified Complete TMA Response
timeFrame: Through 26 weeks
Secondary outcomes:
measure: Percentage of Patients With Complete Hematologic Response
timeFrame: Through 26 weeks
measure: Percentage of Patients With Platelet Count Normalization
timeFrame: Through 26 weeks
measure: Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
timeFrame: Through 26 weeks
measure: Platelet Count Change From Baseline to 26 Weeks
timeFrame: Through 26 weeks
measure: Percentage of Patients With Complete TMA Response
timeFrame: Through End of Study, Median Exposure 52 Weeks
measure: Percentage of Patients With Modified Complete TMA Response
timeFrame: Through End of Study, Median Exposure 52 Weeks
measure: Percentage of Patients With Complete Hematologic Response
timeFrame: Through End of Study, Median Exposure 52 Weeks
measure: Percentage of Patients With Platelet Count Normalization
timeFrame: Through End of Study, Median Exposure 52 Weeks
measure: Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
timeFrame: Through End of Study, Median Exposure 52 Weeks
measure: Platelet Count Change From Baseline to 52 Weeks
timeFrame: Through 52 Weeks
Other outcomes:
Locations:
city: Burlington
country: United States
state: Massachusetts
city: Hackensack
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Columbus
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: Liège
country: Belgium
city: Caen
country: France
city: Lille
country: France
city: Nantes
country: France
city: Nice
country: France
city: Paris
country: France
city: Paris
country: France
city: Toulouse
country: France
city: Tours
country: France
city: Essen
country: Germany
city: Hannover
country: Germany
city: Bergamo
country: Italy
city: Firenze
country: Italy
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Exeter
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle
country: United Kingdom
Study officials:
References:
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.
citation: Cofiell 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.