Autoimmune-haemolytic Anemia Antiphospholipid Syndrome Immune-mediated Thrombocytopenia MedDRA version: 20.0 Level: LLT Classification code 10003825 Term: Autoimmune hemolytic anemia System Organ Class: 100000154058 MedDRA version: 20.0 Level: LLT Classification code 10023095 Term: ITP System Organ Class: 100000157088 MedDRA version: 20.0 Level: PT Classification code 10002817 Term: Antiphospholipid syndrome System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: Mabthera or biosimilar Rituximab
Product Name: Rituximab
Product Code: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 17472
Sponsors
Medical University of Vienna, Department of Internal medicine I
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed informed consent obtained before any trial related activities • Ability to understand the nature and the purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the trial • Men or women aged =18 years of age with a diagnosis of autoimmune-mediated haemolytic anemia, antiphospholipid syndrome or immune-mediated thrombocytopenia • In female subjects either childbearing potential terminated by surgery or one year post- menopausal, or a negative urine pregnancy test during screening and the willingness not to become pregnant during the entire study period by practicing reliable methods of contraception • Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant • Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: • Previous treatment with rituximab, obinutuzumab, ofatumumab or ocrelizumab within 12 months • Clinically relevant infection (1 drinks/day, defined according to USDA Dietary Guidelines) • Pregnancy (positive pregnancy test at screening or during study phase), lactation or unreliable contraception in female subjects with child-bearing potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Autoimmune haemolytic anaemia, antiphospholipid syndrome: To investigate whether 5mg/m2, 20mg or 50mg rituximab suffice to suppress CD20+ cells over a defined period of time Immune-mediated thrombocytopenia: to investigate whether repetitive infusions of 50mg rituximab over 2 years (8 every 3 months) reduce the relapse rate of rituximab treated patients, which according to published data is 38%.;Secondary Objective: To investigate the Pharmacokinetics of very low doses of Rituximab To investigate the immunogenicity of very low doses of Rituximab To calculate the drug cost reduction of our treatment regimen To investigate the safety of very low doses of Rituximab To investigate the effects of very low doses of Rituximab on hemolysis specific parameters and hemoglobin To investigate CD20+ cell counts in patients with immune-mediated thrombocytopenia To investigate platelet counts and response to rituximab treatment in patients with immune-mediated thrombocytopenia To investigate platelet function after infusion of rituximab To investigate antibody levels directed against platelets (immune-mediated thrombocytopenia) To investigate Cardiolipin-, beta2-glycoprotein-I-, antiphospholipid- antibody levels and lupus anticoagulant in patients with anitphospholipid syndrome To investigate coagulation specific biomarkers in those patients with antiphospholipid syndrome ;Primary end point(s): Antiphospholipid Syndrome and Autoimmune haemolytic anaemia: CD19/20+ cell counts Immune-mediated Thrombocytopenia: Relapse rate;Timepoint(s) of evaluation of this end point: Antiphospholipid Syndrome, Autoimmune-haemolytic anaemia: baseline, End of each infusion, +2h after infusion potentially +24h and +7d after first infusion before 2nd infusion before 3rd infusion during end-of-study visit Immune-mediated Thrombocytopenia: End of study visit (2 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - plasma concentrations of rituximab - Immunogenicity (neutralizing anti-drug antibodies, human antichimeric antibodies) - Safety (Laboratory data and adverse events) - Platelet counts and reticulated platelets - hemoglobin levels, hemolysis specific parameters -antibody levels (antiphospholipid-specific antibodies, anti-platelet antibodies) - platelet function - coagulation specific tests in patients with immune-mediated thrombocytopenia - immune-mediated thrombocytopenia: response: permanent suppression of CD20+ cell counts, platelet counts, complete response (defined as platelets above 100 G/L), complete sustained response (permanent platelet count >100 G/L), partial response (platelets 50-100 G/L) for patients with initial platelet counts 50% reduction in platelet counts or platelet counts <30G/L after initial response or need for further treatment, relapse-free survival, treatment free survival (need for further treatment, usually at <30 G/L);Timepoint(s) of evaluation of this end point: - PK at each visit to the ward (baseline, end of each infusion and 1 and 2h thereafter, control visits) - AE, Safety, (baseline, end of each infusion and 1 and 2h thereafter, control visits) - Immunogenicity: Baseline of each study day -hemoglobin levels: Trial day 1 each time-point, and baseline of all other trial days, all control visits - hemolysis specific data: baseline of each study day and all control visits - antibody levels: at each visit - platelet function: during first two infusions - coagulation specific biomarkers: every visit - response at 1, 3, 6 months -CD20+ cells: each visit | — |
Countries
Austria
Contacts
Public ContactDepartment of Clinical Pharmacology
Medical University of Vienna, Department of Clinical Pharmacology
Outcome results
None listed