Efficacy and Safety of Subcutaneous Belimumab or Placebo in Addition of Rituximab in Persistent or Chronic Immune Thrombocytopenia

Inclusion Criteria:

1. Age ≥ 18 years
2. Primary ITP defined according to the standard definition criteria (Rodeghiero, Blood

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 arelapse.
4. Platelet count ≤ 30 x 109/L within the previous month or <50 x 109/L if presence ofhaemorrhagic events or other reason left up to investigator discretion.
5. ITP duration of more than 2 months but less than 5 years from diagnosis.
6. Normal bone marrow smear for patients above 60 years of age
7. Negative pregnancy test results and effective contraception for women of childbearingage Female subjects of childbearing potential must not become pregnant and so must besexually inactive by abstinence or use contraceptive methods with a failure rate of < 1%. Therefore, these women must have a negative serum pregnancy test at screening, andconfirmed monthly while in study (with serum or Urine test), out to at least 12 months (taking account of the longest half-life which is that of 29.7 days and according tosmPC) post last dose and agree to 1 of the following:

• Complete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent until 16 weeks after the last dose of study agent (Sexualinactivity by abstinence must be consistent with the preferred and usuallifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation,symptothermal, post-ovulation methods) and withdrawal are not acceptable methodsof contraception) OR
• Consistent and correct use of 1 of the following acceptable methods of birthcontrol for 1 month prior to the start of the study agent, during the study, and 16 weeks after the last dose of study agent
• Oral contraceptive, either combined or progestogen alone
• Injectable progestogen
• Implants of levonorgestrel or etonogestrel
• Estrogenic vaginal ring
• Percutaneous contraceptive patches
• Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure rateas stated in the product label
• Male partner sterilization (vasectomy with documentation of azoospermia)prior to the female subject's entry into the study, and this male is thesole partner for that subject. For this definition, "documented" refers tothe outcome of the investigator's/designee's medical examination of thesubject or review of the subject's medical history for study eligibility, asobtained via a verbal interview with the subject or from the subject'smedical records
• Double barrier method: condom and occlusive cap (diaphragm or cervical/vaultcaps) plus spermicidal agent (foam/gel/film/cream/suppository) These allowedmethods of contraception are only effective when used consistently,correctly and in accordance with the product label. The investigator isresponsible for ensuring subjects understand how to properly use thesemethods of contraception.

8. Complete Vaccinal scheme against SARS-CoV2 according to the recommendations of thehealth authorities
9. Gammaglobulin level ≥ 7 g/L
10. Informed consent
11. Affiliated to, or beneficiary of, a social security regime or similar

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 3 months before inclusion
6. Previous anaphylactic shock to previous biologic therapy
7. Chronic or ongoing severe infection requiring treatment or hospitalization in the 60days preceding inclusion.
8. Use of parenteral antibiotics within 60 days, current use of suppressive therapy forchronic infection such as tuberculosis, pneumocystis, cytomegalovirus, HSZ, herpeszoster, and atypical mycobacteria
9. Evidence of serious suicide risk including any history of suicidal behavior in thelast 6 months and/or any suicidal ideation in the last 2 months or who in theinvestigator's judgment, pose a significant suicide risk.
10. Psychiatric Illness impairing judgement.
11. Neutrophils count < 1,000/mm3 at inclusion
12. Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B virussurface antigen or core antibody (HbsAg or HBcAb)
13. Impaired renal function as indicated by a serum creatinine level > 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 leukoencephalopathy
18. Previous history of major organ transplant or hematopoietic stem cell/marrowtransplant 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 inclusionin study
22. History of significant medical illness or clinically significant laboratoryabnormality (or planned surgical procedure) which in the opinion of the investigatorwould interfere with the study procedures and / or assessments or compromise subjectsafety
23. Body mass index > 40
24. PCR-confirmed SARS-CoV-2 infection
25. Vulnerable persons, under the protection of justice,
26. Persons deprived of their liberty by judicial or administrative decision,
27. Persons admitted to a health or social establishment for purposes other than research,
28. Persons under legal protection (guardianship, curatorship),
29. Persons unable to express their consent