Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00838513
First received: February 3, 2009
Last updated: January 19, 2015
Last verified: January 2015

February 3, 2009
January 19, 2015
July 2009
October 2010   (final data collection date for primary outcome measure)
  • Assess the Effect of Eculizumab on TMA Event-free Status [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    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.
  • Assess the Effect of Eculizumab to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Hematologic Normalization [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    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.
  • Assess the Effect of Eculizumab to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Complete TMA Response [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    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.
Assess the effect of eculizumab on thrombotic microangiopathy (TMA). [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00838513 on ClinicalTrials.gov Archive Site
  • Additional Efficacy Endpoints Related to Manifestations of TMA as Assessed by TMA Intervention Rate [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
    TMA Intervention Rate (# PE/PI and # Dialysis Events/Patient/Day) in the eculizumab treatment period (from baseline through 26 weeks) for PE/PI and (from the fifteenth day following the first eculizumab dose through 26 weeks) for new dialysis events was compared with the TMA Intervention Rate during the pre-eculizumab treatment period.
  • Assess the Effect of Eculizumab to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Platelet Count Change From Baseline [ Time Frame: From Baseline Through 26 Weeks ] [ Designated as safety issue: No ]
  • Assess the Effect of Eculizumab to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Platelet Count Normalization [ Time Frame: Through 26 Weeks ] [ Designated as safety issue: No ]
    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
  • Assess the Effect of Eculizumab on TMA Event-free Status [ Time Frame: Through End of Study, Median Exposure 156 Weeks ] [ Designated as safety issue: No ]
    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.
  • Assess the Effect of Eculizumab to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Hematologic Normalization [ Time Frame: Through End of Study, Median Exposure 156 Weeks ] [ Designated as safety issue: No ]
    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.
  • Assess the Effect of Eculizumab to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Complete TMA Response [ Time Frame: Through End of Study, Median Exposure 156 Weeks ] [ Designated as safety issue: No ]
    The proportion of patients who achieved a Complete TMA Response from baseline through end of study 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.
  • Additional Efficacy Endpoints Related to Manifestations of TMA as Assessed by TMA Intervention Rate [ Time Frame: Through End of Study, Median Exposure 156 Weeks ] [ Designated as safety issue: No ]
    TMA Intervention Rate (# PE/PI and # Dialysis Events/Patient/Day) in the eculizumab treatment period (from baseline through end of study) for PE/PI and (from the fifteenth day following the first eculizumab dose through end of study) for new dialysis events was compared with the TMA Intervention Rate during the pre-eculizumab treatment period.
  • Assess the Effect of Eculizumab to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Platelet Count Change From Baseline [ Time Frame: From Baseline Through End of Study, Median Exposure 156 Weeks ] [ Designated as safety issue: No ]
  • Assess the Effect of Eculizumab to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Platelet Count Normalization [ Time Frame: Through End of Study, Median Exposure 156 Weeks ] [ Designated as safety issue: No ]
    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 Not specified.
  • Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration [ Time Frame: Induction Phase for 4 weeks followed by Maintenance Phase starting on Week 5 through 26 weeks or longer. ] [ Designated as safety issue: No ]
  • Additional efficacy endpoints related to manifestations of TMA. [ Time Frame: Through 26 weeks ] [ Designated as safety issue: No ]
  • Overall safety and tolerability of eculizumab [ Time Frame: Through 26 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) and pharmacodynamics (PD) of eculizumab in patients with aHUS. [ Time Frame: Through 26 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS)
An Open-label, Multi-center Controlled Clinical Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (AHUS)

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

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Atypical Hemolytic Uremic Syndrome
Drug: 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.
Experimental: eculizumab
Intervention: Drug: eculizumab
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, Nürnberger 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
December 2013
October 2010   (final data collection date for primary outcome measure)

Inclusion Critera:

  1. Male or female patients' ≥18 years of age who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).
  2. 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 first dose of IP.
  3. 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.
  4. Known complement regulatory protein genetic abnormality.
  5. 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.
  6. Creatinine level ≥ ULN for age.
  7. 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.
  8. Able to give written informed consent.
  9. Able and willing to comply with study procedures.

Exclusion Criteria:

  1. 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.
  2. Malignancy within 5 years of screening.
  3. Typical HUS (Shiga toxin +).
  4. Known HIV infection.
  5. Identified drug exposure-related HUS.
  6. Infection-related HUS.
  7. HUS related to bone marrow transplant.
  8. HUS related to vitamin B12 deficiency.
  9. Patients with a confirmed diagnosis of sepsis.
  10. 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.
  11. Pregnancy or lactation.
  12. Unresolved meningococcal disease.
  13. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
  14. 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.
  15. Patients who have received previous treatment with eculizumab.
  16. Patients receiving IVIg within 8 weeks or Rituximab therapy within 12 weeks of the screening visit.
  17. Patients receiving other immunosuppressive therapies such as steroids, mTOR inhibitors or tacrolimus are excluded unless: [1] part of an established post-transplant anti-rejection regime, [2] patient has confirmed anti-CFH antibody requiring immunosuppressive therapy, and [3] dose of such medications have been unchanged for at least 4 weeks prior to the screening period and throughout the Observation Period or [4] patient is experiencing an acute aHUS relapse immediately after transplant.
  18. Patients receiving Erythrocyte Stimulating Agents (ESAs) unless already on a stable dose for at least 4 weeks prior to the screening period, or a washout period of at least 2 weeks from the last dose of ESA therapy.
  19. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedures beginning 4 weeks prior to screening and throughout the entire trial.
  20. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedures beginning 4 weeks prior to screening and throughout the entire trial.
  21. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada,   France,   Germany,   Italy,   Netherlands,   Sweden,   United Kingdom
Spain,   United States,   Austria,   Switzerland
 
NCT00838513
C08-003A, BB-IND 11075, EudraCT Number 2008-006954-17
Yes
Alexion Pharmaceuticals
Alexion Pharmaceuticals
Not Provided
Not Provided
Alexion Pharmaceuticals
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP