Clinical trial NCT01757431: The Safety and Efficacy of Eculizumab in Japanese Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atypical Hemolytic Uremic Syndrome (aHUS)
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-12-31
Enrollment: 2
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Protocol is intended to characterize the overall safety and tolerability of eculizumab in this population.


Eligibility criteria: Inclusion Criteria:

1. All patients with diagnosis of aHUS who have been receiving eculizumab by personal importation (specific eligibility criteria below do not apply) Or,
2. Patients with current clinical manifestations of aHUS who meet the following criteria:

   1. Patient with diagnosis of aHUS with or without an identified complement regulatory protein genetic abnormality or anti-complement factor antibody and for whom other known etiologies of hemolytic uremic syndrome (HUS) have been ruled out as confirmed in the Exclusion Criteria
   2. Patient (and legal guardian if patient is not an adult) willing and able to give written informed consent and assent (or verbal assent if patient is unable to read or write)
   3. Patient at least 1 month of age and body weight ≥5 kg
   4. Platelet count at screening \< lower limit of normal (LLN)
   5. Signs or symptoms of hemolysis (i.e., lactate dehydrogenase (LDH) ≥ 1.5x upper limit of normal (ULN) and Hemoglobin ≤ LLN) at start of current aHUS event
   6. Serum Creatinine (SrCr) level ≥ ULN at screening (patient requiring dialysis for acute renal failure also eligible)
   7. Female patient of childbearing potential practicing an effective, reliable and medically approved contraceptive regimen during the entire duration of the study, including the Follow-up Period. At the time of the last follow-up visit, patient must agree to continue to use adequate contraception methods for up to 5 months following discontinuation of eculizumab treatment
   8. Able and willing to comply with study procedures

Exclusion Criteria:

Shiga-toxin producing E. coli-HUS (STEC-HUS; shiga-toxin and/or STEC positive) History of malignancy within 5 years of screening Known human immunodeficiency virus (HIV) infection Identified drug exposure-related HUS Infection-related HUS HUS related to bone marrow transplant (BMT) HUS related to vitamin B12 deficiency Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or syndrome Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage renal disease (ESRD)) Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within 7 days of the screening visit and not treated with antibiotics to which the organism is sensitive 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 systemic meningococcal disease Any medical or psychological condition that, in the opinion of the investigator, could increase patient's risk by participating in the study or confound the outcome of the study Patients receiving chronic intravenous immunoglobulin (IVIG) within 8 weeks unless for unrelated medical condition (e.g., hypogammaglobulinemia) or chronic rituximab therapy within 12 weeks of the screening visit Patients receiving other immunosuppressive therapies such as steroids, calcineurin inhibitors (mTOR), (e.g., cyclosporine or tacrolimus) are excluded unless: \[1\] part of an established post-transplant anti-rejection regimen, or \[2\] patient has confirmed anti-Complement Factor Antibodies requiring immunosuppressive therapy or \[3\] steroids are used for a condition other than aHUS (e.g., asthma) Prior eculizumab use, hypersensitivity to eculizumab, to murine proteins or to one of the excipients Inclusion in any other investigational intervention trial except this study

Primary outcomes:
measure: Adverse events and serious adverse events and their severity and relationship to the drug
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Nagano
country: Japan
facility: Nagano Red Cross Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical and Dental University Hospital
Study officials:
References:
citation: 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.