Very low doses of Rituximab for autoimmune diseases, for which rituximab is not approved for - a Pilot Trial

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2016-002478-11-AT
• Date of registration: 01/07/2016
• Prospective Registration: Yes
• Primary sponsor: Medical University of Vienna, Department of Internal medicine I
• Public title: Very low doses of Rituximab for autoimmune diseases, for which rituximab is not approved for - a Pilot Trial
• Scientific title: Very low doses of Rituximab for off-label treatment – a Pilot Trial - Low_Rituximab
• Date of first enrolment: 19/07/2016
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002478-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria

Contacts

• Name: Department of Clinical Pharmacology
• Affiliation: Medical University of Vienna, Department of Clinical Pharmacology

• Name: Department of Clinical Pharmacology
• Affiliation: Medical University of Vienna, Department of Clinical Pharmacology

Key inclusion & exclusion 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:
• Previous treatment with rituximab, obinutuzumab, ofatumumab or ocrelizumab within 12 months
• Clinically relevant infection (<1 week)
• Intravenous immunoglobulins, unless cyclic thrombocytopenia occures
• Relevant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, hematological, endocrine, inflammatory or neurological diseases, that may interfere with the aim of the study
• Ascertained or presumed hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or major allergic reactions in general, which the investigator considers may compromise the safety of the participants
• Use of medication during 2 weeks before the start of the study, which the investigator considers may affect the validity of the study
• Drug abuse, alcohol (>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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

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

Intervention(s)

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: 174722-31-7
Current Sponsor code: Rituximab
Other descriptive name: Rituximab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

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%.

Primary end point(s): Antiphospholipid Syndrome and Autoimmune haemolytic anaemia: CD19/20+ cell counts
Immune-mediated Thrombocytopenia:
Relapse rate

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

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 Outcome(s)

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 G/L, as stable patients will also be included a 50% increase in platelet counts from baseline platelet count will be considered as response, overall response (includes the before mentioned responses), patients with platelets <30 G/L are defined as non-responders; response at 1, 3, 6 months, time to complete response, relapse will be defined as >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

Secondary ID(s)

2.0

Source(s) of Monetary Support

Medical University of Vienna, Department of Clinical Pharmacology

Ethics review

Status: Approved
Approval date: 08/07/2016
Contact: