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

NCT01194973 | Completed Phase 2 Results DMC

• 1 other identifier: C10-004
• Study Type: interventional
• Target: 44
• Locations: 7 countries
• Sites: 23

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

Keywords

Atypical Hemolytic-Uremic Syndrome

Outcome Measures

Primary Outcomes (2)

• Percentage of Patients With Complete TMA Response

  Proportion of Patients with Complete TMA response was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as \< 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.

  Through 26 weeks

• Percentage of Patients With Modified Complete TMA Response

  Proportion of Patients with Modified Complete TMA response through 26 weeks of treatment was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as ≥ 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.

  Through 26 weeks

Secondary Outcomes (10)

• Percentage of Patients With Complete Hematologic Response

  Through 26 weeks

• Percentage of Patients With Platelet Count Normalization

  Through 26 weeks

• Percentage of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement

  Through 26 weeks

• Platelet Count Change From Baseline to 26 Weeks

  Through 26 weeks

• Percentage of Patients With Complete TMA Response

  Through End of Study, Median Exposure 52 Weeks

Study Arms (1)

Eculizumab

EXPERIMENTAL

Drug: Eculizumab

Interventions

Eculizumab 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.

Eculizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be willing and able to give written informed consent.
• Patient's age \> 18 years.
• Patients exhibit thrombocytopenia, hemolysis and elevated Serum Creatinine.

You may not qualify if:

• 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.
• Able and willing to comply with study procedures
• Chronic dialysis.
• Prior eculizumab use or hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
• Known familial a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) deficiency (ADAMTS-13 \<5%).
• Typical Hemolytic-Uremic Syndrome (HUS) (known Shiga toxin +).
• History of malignancy within 5 years of screening.
• Known human immunodeficiency virus (HIV) infection.
• Identified drug exposure-related hemolytic-uremic syndrome (HUS).
• Infection-related HUS.
• HUS related to bone marrow transplant (BMT).
• HUS related to vitamin B12 deficiency.
• Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
• 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.
• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (23)

Unknown Facility

Burlington, Massachusetts, 01805, United States

Location

Unknown Facility

Hackensack, New Jersey, 07601, United States

Location

Unknown Facility

New York, New York, 10032, United States

Location

Unknown Facility

Columbus, Ohio, 43210, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Liège, 4020, Belgium

Location

Unknown Facility

Caen, 14033, France

Location

Unknown Facility

Lille, 59037, France

Location

Unknown Facility

Nantes, 44093, France

Location

Unknown Facility

Nice, 6000, France

Location

Unknown Facility

Paris, 75743, France

Location

Unknown Facility

Paris, 75970, France

Location

Unknown Facility

Toulouse, 31059, France

Location

Unknown Facility

Tours, 37044, France

Location

Unknown Facility

Essen, 45147, Germany

Location

Unknown Facility

Hanover, 30625, Germany

Location

Unknown Facility

Bergamo, 24127, Italy

Location

Unknown Facility

Florence, 50134, Italy

Location

Unknown Facility

Barcelona, 14004, Spain

Location

Unknown Facility

Córdoba, 14004, Spain

Location

Unknown Facility

Exeter, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Unknown Facility

Newcastle, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33783815 DERIVED

• 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.

  PMID: 25833956 DERIVED

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Hemolytic-Uremic Syndrome; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc
• Organization: Alexion Pharmaceuticals Inc

clinicaltrials@alexion.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2010
• First Posted: September 3, 2010
• Study Start: July 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: February 1, 2014
• Last Updated: May 30, 2017
• Results First Posted: April 24, 2015

Record last verified: 2015-04

Locations

DE (2); US (5); FR (8); BE (1); IT (2); ES (2); GB (3)