An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome

NCT01193348 | Completed Phase 2 Results DMC

• 1 other identifier: C10-003
• Study Type: interventional
• Target: 22
• Locations: 9 countries
• Sites: 17

Brief Summary

The primary purpose is to assess the efficacy and safety of eculizumab in pediatric patients with aHUS to control TMA as characterized by thrombocytopenia, hemolysis and renal impairment.

Conditions

Atypical Hemolytic-Uremic Syndrome

Keywords

Atypical Hemolytic-Uremic Syndrome

Outcome Measures

Primary Outcomes (1)

• Proportion 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 ≥ 25% improvement in serum creatinine from baseline which was sustained for at least two consecutive measurements obtained at least four weeks apart).

  Through 26 weeks

Secondary Outcomes (14)

• Proportion of Patients With Complete Hematologic Response

  Through 26 weeks

• Proportion of Patients With Platelet Count Normalization

  Through 26 weeks

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

  Through 26 weeks

• Platelet Count Change From Baseline to 26 Weeks

  Through 26 weeks

• Proportion of Patients With Complete TMA Response

  Through End of Study, Median Exposure 55 Weeks

Study Arms (1)

Eculizumab

EXPERIMENTAL

Drug: Eculizumab

Interventions

Eculizumab DRUG

Fixed dosing is based on body weight cohorts. Adjustment of dose to accommodate patient growth is possible.

Eculizumab

Eligibility Criteria

• Age: 1 Month - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient's parent/legal guardian must have been willing and able to give written informed consent and the patient must have been willing to give written informed assent (if applicable as determined by the central IRB/IEC).
• Pediatric patients with aHUS: Patients could have been newly diagnosed, or with previously diagnosed disease, or post-kidney transplant with the disease.
• Patients one month to 18 years and body weight ≥ 5kg.
• Platelet count at screening and baseline visit must have been below lower limit of normal (\<LLN). If screening visit and baseline visit are combined into one day, an additional platelet count value obtained at least 24 hours before screening/baseline sample must also be \<LLN.
• Exhibited signs or symptoms of hemolysis at start of current aHUS event (i.e., lactate dehydrogenase (LDH) ≥1.5 x Upper Limit of Normal \[ULN\] and hemoglobin ≤LLN), fragmented RBC with a negative Coombs test.
• Serum Creatinine level ≥97 percentile for age at screening (patients requiring dialysis for acute renal failure are also eligible).

You may not qualify if:

• Patients must have been vaccinated against N. meningitidis, pneumococcus and haemophilus (per the vaccine label) at least 14 days prior to study drug initiation or otherwise be protected by prophylactic antibiotics. Patients under age two years were to receive antibiotic prophylaxis throughout the treatment period.
• Female patients of childbearing potential (female patients who have achieved menarche) must have been 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 have agreed to continue to use adequate contraception methods for up to five months following discontinuation of eculizumab treatment.
• Able and willing to comply with study procedures
• Known familial ADAMTS-13 deficiency (ADAMTS-13 \<5%).
• Shiga toxin E.coli-related hemolytic uremic syndrome (STEC-HUS \[known Shiga toxin + E.coli\]).
• History of malignancy within five years of screening.
• Known human immunodeficiency virus (HIV) infection.
• Identified drug exposure-related 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.
• Plasma Therapy for \>5 weeks prior to enrollment.
• Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage renal disease \[ESRD\]).
• Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within seven days of the screening visit and not treated with antibiotics to which the organism is sensitive.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (17)

Unknown Facility

Atlanta, Georgia, 30322, United States

Location

Unknown Facility

Hackensack, New Jersey, 07601, United States

Location

Unknown Facility

Corpus Christi, Texas, 78411, United States

Location

Unknown Facility

Spokane, Washington, 99204, United States

Location

Unknown Facility

North Adelaide, South Australia, 5006, Australia

Location

Unknown Facility

Ghent, 9000, Belgium

Location

Unknown Facility

Toronto, Ontario, M5G1X8, Canada

Location

Unknown Facility

Lille, 59800, France

Location

Unknown Facility

Marseille, 13385, France

Location

Unknown Facility

Paris, 75935, France

Location

Unknown Facility

Rouen, 76000, France

Location

Unknown Facility

Hanover, 30625, Germany

Location

Unknown Facility

Milan, Italy

Location

Unknown Facility

Palermo, 90134, Italy

Location

Unknown Facility

Nijmegen, 6525, Netherlands

Location

Unknown Facility

London, United Kingdom

Location

Unknown Facility

Nottingham, 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

• Tschumi S, Gugger M, Bucher BS, Riedl M, Simonetti GD. Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and histological findings. Pediatr Nephrol. 2011 Nov;26(11):2085-8. doi: 10.1007/s00467-011-1989-4. Epub 2011 Aug 30.

  PMID: 21877169 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@alxn.com

clinicaltrials@alxn.com

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• 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 1, 2010
• Study Start: September 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 29, 2015
• Results First Posted: April 29, 2015

Record last verified: 2015-04

Locations

BE (1); DE (1); FR (4); GB (2); CA (1); IT (2); NL (1); AU (1); US (4)