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Completed

NCT Number: NCT00844545

Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS

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

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Key information

Conditions

Atypical Hemolytic Uremic Syndrome Anemia Anemia, Hemolytic Blood Platelet Disorders Cytopenia Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hematologic Diseases Hemic and Lymphatic Diseases Hemolytic-Uremic Syndrome Kidney Diseases Male Urogenital Diseases Thrombocytopenia Thrombotic Microangiopathies Uremia Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Innsbruck, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Exclusion criteria

  • 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
  • Patients who have received previous treatment with eculizumab
  • Patients receiving IVIG within 8 weeks or Rituximab therapy within 12 weeks of screening.
  • 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
  • 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.
  • 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.
  • Hypersensitivity to eculizumab, to murine proteins or to one of the excipients

Treatment and study plan

Eculizumab

Drug

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

Primary outcomes

  1. Platelet Count Change From Baseline to 26 Weeks

    Time frame: From Baseline to 26 weeks

  2. Percentage of Patients With Platelet Count Normalization

    Time frame: Through 26 weeks

    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.

  3. Percentage of Patients With Hematologic Normalization

    Time frame: Through 26 weeks

    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.

Secondary outcomes

  1. Percentage of Patients With Complete TMA Response

    Time frame: Through 26 weeks

    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 as ≥25% reduction from baseline in serum creatinine), which was sustained for two consecutive measurements over a period of at least four weeks.

  2. TMA Intervention Rate

    Time frame: Through 26 weeks

    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.

  3. Platelet Count Change From Baseline to 156 Weeks

    Time frame: From Baseline to 156 Weeks

  4. Percentage of Patients With Platelet Count Normalization

    Time frame: Through End of Study, Median Exposure 100.29 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.

  5. Percentage of Patients With Hematologic Normalization

    Time frame: Through End of Study, Median Exposure 100.29 Weeks

    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.

  6. Percentage of Patients With Complete TMA Response

    Time frame: Through End of Study, Median Exposure 100.29 Weeks

    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.

  7. TMA Intervention Rate

    Time frame: Through End of Study, Median Exposure 100.29 Weeks

    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.

  8. 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.

Sponsors and collaborators

Lead sponsor

Alexion Pharmaceuticals, Inc.

Industry

Registry information

Official study title

An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (aHUS)

Acronym: aHUS

Important dates

Study start
2009
Primary completion
2010
Study completion
2013
First posted
Feb 16, 2009
Registry last updated
Jul 23, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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