NCT00844428

Brief Summary

The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of adolescent patients with plasma therapy-sensitive Atypical Hemolytic-Uremic Syndrome (aHUS).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2009

Typical duration for phase_2

Geographic Reach
7 countries

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 12, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 16, 2009

Completed
5 months until next milestone

Study Start

First participant enrolled

July 1, 2009

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2010

Completed
3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2013

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

January 26, 2015

Completed
Last Updated

July 23, 2015

Status Verified

June 1, 2015

Enrollment Period

1.3 years

First QC Date

February 12, 2009

Results QC Date

December 15, 2014

Last Update Submit

June 30, 2015

Conditions

Atypical Hemolytic Uremic Syndrome

Outcome Measures

Primary Outcomes (3)

  • Percentage of Patients With TMA Event-free Status

    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.

    Through 26 weeks

  • Percentage of Patients With Hematologic Normalization

    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.

    Through 26 weeks

  • Percentage of Patients With Complete TMA Response

    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.

    Through 26 weeks

Secondary Outcomes (10)

  • TMA Intervention Rate

    Through 26 weeks

  • Platelet Count Change From Baseline to 26 Weeks

    From Baseline to 26 Weeks

  • Percentage of Patients With Platelet Count Normalization

    Through 26 Weeks

  • Percentage of Patients With TMA Event-free Status

    Through End of Study, Median Exposure 156 Weeks

  • Percentage of Patients With Hematologic Normalization

    Through End of Study, Median Exposure 156 Weeks

  • +5 more secondary outcomes

Study Arms (1)

Eculizumab

EXPERIMENTAL
Drug: eculizumab

Interventions

eculizumabDRUG

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

Age12 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Male or female patients between ages from 12 and up to 18 years of age weighing ≥ 40 kg who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).
  • Patients must be receiving PT for aHUS and must be observed to receive ≥ 1 PT treatment every two weeks and no more than 3 PT treatments/week (at an unchanged frequency) for at least 8 weeks before the first dose of IP.
  • Platelet Count Pre-PT Baseline Set-Point (collected in the hours before the Qualifying PT Episode) is within 75% of the average of the pre-PT platelet counts collected at Screening and during the Observation Period.
  • Known complement regulatory protein genetic abnormality.
  • Lactate dehydrogenase (LDH) level at screening or at the onset of the current aHUS episode was ≥ ULN. If LDH is normal at screening, other markers indicative of ongoing hemolysis such as haptoglobin, schistocytes should be evaluated and discussed with Sponsor.
  • Creatinine level ≥ ULN for age.
  • 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 and for up to 5 months following eculizumab treatment discontinuation.
  • Patient's parents/legal guardian must be willing and able to give written informed consent and patient must be willing to give written informed assent (if applicable as determined by the IRB/IEC).
  • Able and willing to comply with study procedures.

You may not qualify if:

  • 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.
  • Malignancy within 5 years of screening.
  • Typical HUS (Shiga toxin +).
  • Known HIV infection.
  • Identified drug exposure-related HUS.
  • Infection-related HUS.
  • HUS related to bone marrow transplant.
  • HUS related to vitamin B12 deficiency.
  • Patients with a confirmed diagnosis of sepsis.
  • 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.
  • Pregnancy or lactation.
  • Unresolved meningococcal disease.
  • Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
  • 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.
  • Patients who have received previous treatment with eculizumab.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Unknown Facility

Toronto, Canada

Location

Unknown Facility

Bois-Guillaume, 76230, France

Location

Unknown Facility

Bordeaux, 33076, France

Location

Unknown Facility

Lyon, 69437, France

Location

Unknown Facility

Nantes, 44093, France

Location

Unknown Facility

Paris, 75743, France

Location

Unknown Facility

Starsbourg, 67091, France

Location

Unknown Facility

Hanover, 30625, Germany

Location

Unknown Facility

Genova, 16147, Italy

Location

Unknown Facility

Nijmegen, Netherlands

Location

Unknown Facility

Stockholm, 14186, Sweden

Location

Unknown Facility

Exeter, United Kingdom

Location

Unknown Facility

Glasgow, 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: 33783815DERIVED

  • Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nurnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. doi: 10.1056/NEJMoa1208981.

    PMID: 23738544DERIVED

MeSH Terms

Conditions

Atypical Hemolytic Uremic Syndrome

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Hemolytic-Uremic SyndromeUremiaKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesThrombotic MicroangiopathiesThrombocytopeniaBlood Platelet DisordersCytopenia

Results Point of Contact

Title
Alexion Pharmaceuticals, Inc.
Organization
Alexion Pharmaceuticals, Inc.
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

February 12, 2009

First Posted

February 16, 2009

Study Start

July 1, 2009

Primary Completion

October 1, 2010

Study Completion

December 1, 2013

Last Updated

July 23, 2015

Results First Posted

January 26, 2015

Record last verified: 2015-06

Locations

DE(1)CA(1)IT(1)FR(6)NL(1)SE(1)GB(2)