NCT00844844

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-resistant Atypical Hemolytic-Uremic Syndrome (aHUS).

Trial Health

93
On Track

Trial Health Score

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

Enrollment
1

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2009

Typical duration for phase_2

Geographic Reach
5 countries

17 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 13, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 16, 2009

Completed
2 months until next milestone

Study Start

First participant enrolled

May 1, 2009

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2010

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2013

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

December 3, 2014

Completed
Last Updated

July 23, 2015

Status Verified

June 1, 2015

Enrollment Period

1.3 years

First QC Date

February 13, 2009

Results QC Date

October 21, 2014

Last Update Submit

June 30, 2015

Conditions

Atypical Hemolytic Uremic Syndrome

Keywords

aHUS

Outcome Measures

Primary Outcomes (3)

  • Platelet Count Change From Baseline to 26 Weeks

    From Baseline to 26 weeks

  • Percentage of Patients With Platelet Count Normalization

    The primary objective of the study (per protocol) was to assess the effect of eculizumab to reduce TMA as measured by platelet count change from baseline (BL) during the Treatment Period (26 weeks) in patients with plasma therapy (PT)-resistant aHUS (protocol defined), including assessment of the proportion of patients who achieved Platelet Count Normalization from baseline through 26 weeks. Platelet Count Normalization was defined as the platelet count observed to be ≥150 x 10\^9/L on at least two consecutive measurements which span a period of at least four weeks.

    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

Secondary Outcomes (8)

  • Percentage of Patients With Complete TMA Response

    Through 26 weeks

  • TMA Intervention Rate

    Through 26 weeks

  • Platelet Count Change From Baseline to 156 Weeks

    From Baseline to 156 Weeks

  • Percentage of Patients With Platelet Count Normalization

    Through End of Study, Median Exposure 100.29 Weeks

  • Percentage of Patients With Hematologic Normalization

    Through End of Study, Median Exposure 100.29 Weeks

  • +3 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 from 12 and up to 18 years weighing ≥ 40 kg who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).
  • Decrease in platelet count despite at least 4 plasma therapy (PT) treatments in the 1 week immediately prior to screening.
  • Screening platelet count , \< 150 x10\^9/L and at least 25% lower than the average remission platelet count or
  • If remission counts not available, platelet count at onset of the current aHUS episode must be ≤75x10\^9/L and platelet count at screening must be ≤ 100 x 10\^9/L despite PT treatment administration of at least 4 PT treatments in the 1 week immediately prior to screening
  • Known complement regulatory protein genetic abnormality
  • Lactate dehydrogenase (LDH) level ≥ ULN unless the patient has been receiving plasma exchange and LDH at the onset of the current aHUS episode was at least the 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 of 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.
  • 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
  • Renal function status requiring chronic dialysis
  • 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.
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Unknown Facility

Atlanta, Georgia, 30322, United States

Location

Unknown Facility

Fort Wayne, Indiana, 46804, United States

Location

Unknown Facility

New York, New York, 10032, United States

Location

Unknown Facility

New York, New York, 10065, United States

Location

Unknown Facility

Grapevine, Texas, 76051, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Innsbruck, 6020, Austria

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

Quimper, 29107, France

Location

Unknown Facility

Saint-Priest-en-Jarez, 42270, France

Location

Unknown Facility

Tours, 37044, France

Location

Unknown Facility

Aachen, 52074, Germany

Location

Unknown Facility

Essen, 45147, Germany

Location

Unknown Facility

Newcastle, NE7 7DN, 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 13, 2009

First Posted

February 16, 2009

Study Start

May 1, 2009

Primary Completion

September 1, 2010

Study Completion

July 1, 2013

Last Updated

July 23, 2015

Results First Posted

December 3, 2014

Record last verified: 2015-06

Locations

US(6)DE(2)AU(1)GB(1)FR(7)