Hematopoietic stem cell transplant-associated thrombotic microangiopathy MedDRA version: 20.0 Level: PT Classification code 10043645 Term: Thrombotic microangiopathy System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Sponsors
Alexion Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.12 years of age or older, at the time of signing the informed consent form (ICF) 2.participants who received HSCT within the past 6 months at the time of Screening 3.A TMA diagnosis, based on all of the following criteria occurring simultaneously: • De novo thrombocytopenia or platelet transfusion refractoriness • De novo anemia or increase in transfusion requirements • Either one of the following markers of hemolysis - LDH > 1.5 × ULN or, - Presence of schistocytes = 2 high power field (HPF) • Proteinuria on spot urinalysis • Presence of hypertension 4.Participants must have HSCT-TMA that persists despite initial management of any triggering condition (persists for at least 72 hours after management of triggering agent/condition) • Withdrawal or dose reduction of the offending agent (eg, CNIs) • Treatment of any underlying infection • Treatment of underlying GVHD 5.Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1.Known familial or acquired ‘a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13’ (ADAMTS13) deficiency (activity < 5%) . 2.Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS) 3.Positive direct Coombs test 4.Diagnosis or suspicion of disseminated intravascular coagulation (DIC) 5.Known bone marrow/graft failure 6.Diagnosis of veno-occlusive disease (VOD), regardless of severity 7.Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer, 8.Unresolved meningococcal disease 9.Presence or suspicion of sepsis (treated or untreated) within 7 days prior to Screening 10.Pregnancy or breastfeeding 11.Hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab 12.Previously or currently treated with a complement inhibitor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of ravulizumab plus BSC versus BSC-only ;Secondary Objective: Safety and tolerability of ALXN1210 and additional efficacy measures;Primary end point(s): TMA response ;Timepoint(s) of evaluation of this end point: Throughout 26 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Time to TMA response 2.Change from baseline in TMA-associated organ dysfunction in renal system, cardiovascular system, pulmonary system, CNS, and GI system at 6 months and 1 year 3.TMA relapse during the study 4.Overall survival at 6 months and 1 year 5.Non-relapse mortality 6.Platelet response;Timepoint(s) of evaluation of this end point: Week 26 and Week 52 | — |
Countries
Australia, Belgium, Canada, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactEuropean Clinical Trial Information
Alexion Europe SAS
Outcome results
None listed