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 Adolescent Patients With Plasma Therapy-Resistant aHUS

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00844844
First received: February 13, 2009
Last updated: November 26, 2014
Last verified: June 2014

February 13, 2009
November 26, 2014
May 2009
September 2010   (final data collection date for primary outcome measure)
  • 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 ]
    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.
  • 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). [ Time Frame: Through 26 Weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00844844 on ClinicalTrials.gov Archive Site
  • Additional Efficacy Endpoints Related to Manifestations of 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.
  • 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: Through End of Study, Median Exposure 100.29 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 ] [ 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 to Reduce Thrombotic Microangiopathy (TMA) as Assessed by Hematologic Normalization [ Time Frame: Through End of Study ] [ 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.
  • Additional Efficacy Endpoints Related to Manifestations of TMA as Assessed by Complete TMA Response [ Time Frame: Through End of Study ] [ Designated as safety issue: No ]
    The proportion of patients who achieved a Complete TMA Response from baseline through end of the study 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 ] [ 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 the study) for PE/PI and (from the fifteenth day following the first eculizumab dose through end of the study) for new dialysis events was compared with the TMA Intervention Rate during the pre-eculizumab treatment period.
  • 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 ]
  • Pharmacokinetics (PK) and pharmacodynamics (PD) of eculizumab in patients with aHUS. [ Time Frame: Through 26 Weeks ] [ Designated as safety issue: Yes ]
  • Overall safety and tolerability of eculizumab. [ Time Frame: Through 26 Weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS
An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (aHUS)

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).

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
1
July 2013
September 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Male or female patients from 12 and up to 18 years weighing ≥ 40 kg who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).
  2. Decrease in platelet count despite at least 4 plasma therapy (PT) treatments in the 1 week immediately prior to screening.

    1. Screening platelet count , < 150 x10^9/L and at least 25% lower than the average remission platelet count or
    2. 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
  3. Known complement regulatory protein genetic abnormality
  4. 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
  5. Creatinine level ≥ ULN for age
  6. 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.
  7. 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.
  8. 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. Renal function status requiring chronic dialysis
  10. Patients with a confirmed diagnosis of sepsis
  11. 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.
  12. Pregnancy or lactation.
  13. Unresolved meningococcal disease.
  14. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome.
  15. 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.
  16. Patients who have received previous treatment with eculizumab
  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 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. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients
  21. Patients between ages from 12 and up to 18 years weighing < 40 kg
Both
12 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Austria,   France,   Germany,   United Kingdom
Italy,   Canada,   Netherlands,   Spain,   Sweden,   Switzerland
 
NCT00844844
C08-002B, BB-IND-11075, EudraCT Number 2008-006953-41
Yes
Alexion Pharmaceuticals
Alexion Pharmaceuticals
Not Provided
Not Provided
Alexion Pharmaceuticals
June 2014

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