An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome

NCT ID: NCT01194973

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2014-02-28

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.

Conditions

Atypical Hemolytic-Uremic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eculizumab

Group Type: EXPERIMENTAL

Eculizumab

Intervention Type: DRUG

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.

Interventions

Eculizumab

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Burlington, Massachusetts, United States

Hackensack, New Jersey, United States

New York, New York, United States

Columbus, Ohio, United States

Houston, Texas, United States

Liège, , Belgium

Caen, , France

Lille, , France

Nantes, , France

Nice, , France

Paris, , France

Paris, , France

Toulouse, , France

Tours, , France

Essen, , Germany

Hanover, , Germany

Bergamo, , Italy

Florence, , Italy

Barcelona, , Spain

Córdoba, , Spain

Exeter, , United Kingdom

London, , United Kingdom

Newcastle, , United Kingdom

Countries

United States; Belgium; France; Germany; Italy; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33783815 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25833956 (View on PubMed)

Other Identifiers

C10-004

Identifier Type: -

Identifier Source: org_study_id