Adults with a definite diagnosis of primary chronic immune thrombocytopeniaaccording to the standard definition. Patients with antinuclear antibodies with no definite criteria for systemic lupus will be eligible. MedDRA version: 23.0 Level: PT Classification code 10083842 Term: Immune thrombocytopenia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: BENLYSTA
Product Name: Bélimumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Belimumab
CAS Number: 356547-88-1
Current Sponsor code: GSK1550188
O
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age = 18 years 2) Primary ITP defined according to the standard definition criteria (Rodeghiero, Blood 2008) 3) Previous response to corticosteroids and/or IgIV defined by a rise of platelet levels > 30 x 109/L with at least a twofold increase from baseline levels followed by a relapse. 4) Platelet count = 30 x 109/L /L at inclusion or 7 g/L 9) Informed consent 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 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: 1) Splenectomy 2) Previous treatment with rituximab or any B-cell targeted therapy 3) Common variable immunodeficiency 4) Previous treatment with cyclophosphamide or ciclosporin 5) Inclusion in another clinical trial less than 1 month before inclusion 6) Previous anaphylactic shock to previous biologic therapy 7) Chronic or ongoing severe infection requiring treatment or hospitalization in the 60 days preceding inclusion. 8) Use of parenteral antibiotics within 60 days, current use of suppressive therapy for chronic infection such as tuberculosis, pneumocystis, cytomegalovirus, HSZ, herpes zoster, and atypical mycobacteria 9) Evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, pose a significant suicide risk. 10) Psychiatric Illness impairing judgement. 11) Neutrophils count 2 mg/dl 14) Liver function: AST (SGOT) and ALT (SGPT) =5xULN Total bilirubin =3 x ULN 15) New York Heart Classification III or IV heart disease 16) Previous history of malignancy in the last 5 years other than cutaneous carcinoma 17) Previous history of Progressive multifocal leukoencephalopathy18) Previous history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant. 19) Alcohol or drug abuse or dependence, either current or within 1year 20) Pregnant or breast-feeding woman 21) Live, attenuated vaccinations must be administered at least 30 days before inclusion in study 22) History of significant medical illness or clinically significant laboratory abnormality (or planned surgical procedure) which in the opinion of the investigator would interfere with the study procedures and / or assessments or compromise subject safety 22) Body mass index > 35 23) Patients under legal protection or unable to consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the superiority at W52 of combination subcutaneous belimumab weekly over a 24 weeks period (Arm A) or subcutaneous placebo weekly during 24 weeks period (Arm B) with rituximab (Mabthera© or biosimilar) (at a fixed dose of 1,000 mg on Day 7 and Days 21).;Secondary Objective: -To analyze the overall response (complete response + response) of patients throughout the study until W104 -To assess the incidence of secondary severe hypogammaglobulinemia (<4 g/dl) in both arms at W12, W24, W36, W52, W88, W104 -To assess levels of gammaglobulin isotypes and subclasses over the course of the study period -To compare in both arms the number of severe infections (requiring hospitalization), over the study period -To assess bleeding events occurring throughout the study -To compare the rate and type anti-platelets antibodies in both arms at baseline and at W24, W52, W104 ;Primary end point(s): Overall response rate (CR + R) in both arms at W52;Timepoint(s) of evaluation of this end point: Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Number and proportion of patients developing a severe hypogammaglobulinemia (gammaglobulin level < 4 g/dl) in both arms at W12, W24, W36, W52, W88, W104 - Duration of severe hypogammaglobulinemia in patients with such complication - Variation in gammaglobulin classes and subclass levels throughout the study (W0, W12, W24, W36, W52, W88, W104) - Number and proportion of severe infections requiring hospitalization during the study - Platelet levels at W6, W12, W24, W36, W52, W88, W104 - Total number and proportion of responders (responders + complete responses) at W6, W12, W 24, W36, W52, W88, W104. - Number and proportion of haemorrhagic events evaluated by the Khellaf Score at W6, W12, W24, W36, W52, W88, W104. - Change from baseline of each B-cell subpopulation, T Follicular helper population and levels of cytokines (including BAFF) at W12, W24, W36, W52, W88, W104 (ancillary study) ;Timepoint(s) of evaluation of this end point: W6, W12, W24, W36, W52, W88, W104. | — |
Countries
France, Italy, Norway, Spain
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Outcome results
None listed