BELIMUMAB for Immune thrombocytopenia

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years\n- Informed consent\n- Affiliated to, or beneficiary of, a social security regime or similar\n- Primary ITP defined according to the standard definition criteria (Rodeghiero, Blood 2008)\n- Previous transient response to first-line treatments of corticosteroids and/or IgIV characterized by a rise of platelet levels > 30 G/L with at least a twofold increase from baseline levels followed by a relapse.\n- Platelet count ≤ 30 x 109/L within the previous month or <50 x 109/L G/L if presence of haemorrhagic events or other reason left up to investigator discretion.\n- ITP duration of more than 2 months but less than 10 years from diagnosis.\n- Negative pregnancy test results and effective contraception for women of childbearing age Female subjects of childbearing potential must not become pregnant and so must be sexually inactive by abstinence or use contraceptive methods with a failure rate of < 1%.\n- Gammaglobulin level ≥ 7 g/L"}

Exclusion criteria

• {"criterion_text":"- Splenectomy\n- Persons deprived of their liberty by judicial or administrative decision\n- Persons admitted to a health or social establishment for purposes other than research\n- Psychiatric Illness impairing judgment\n- Persons under legal protection (guardianship, curatorship),\n- Persons unable to express their consent\n- Common variable immunodeficiency\n- Previous treatment with cyclophosphamide or ciclosporin\n- Inclusion in another clinical trial less than 3 months before inclusion\n- Previous anaphylactic shock\n- Chronic or ongoing severe infection requiring treatment or hospitalization in the 60 days preceding inclusion\n- Previous history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant.\n- 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\n- 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.\n- Neutrophils count < 1,000/mm3 at inclusion\n- Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B virus surface antigen or core antibody (HbsAg or HBcAb)\n- Impaired renal function as indicated by a serum creatinine level > 2 mg/dl\n- Liver function: AST (SGOT) and ALT (SGPT) ≥5xULN Total bilirubin ≥3 x ULN\n- New York Heart Classification III or IV heart disease\n- Previous history of malignancy in the last 5 years other than cutaneous carcinoma\n- Previous history of Progressive multifocal leukoencephalopathy\n- Previous history of Severe cutaneous adverse reactions (Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis)\n- Alcohol or drug abuse or dependence, either current or within 1year\n- Previous treatment with rituximab or any B-cell targeted therapy\n- Pregnant or breast-feeding woman\n- Live, attenuated vaccinations must be administered at least 30 days before inclusion in study\n- 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\n- Body mass index > 40\n- Vulnerable persons, under the protection of justice,"}

Primary endpoints

• {"endpoint_text":"- The overall response rate (CR + R) in both arms at W52","definition_or_measurement_approach":"Measured as overall response rate (complete response + response) at Week 52 (W52) in both arms."}

Secondary endpoints

• {"endpoint_text":"- Total number of responders (responders + complete responses) at W6, W12, W 24, W36, W52, W78, W104.","definition_or_measurement_approach":"Count and proportion of responders (response + complete response) measured at Weeks 6, 12, 24, 36, 52, 78 and 104."}
• {"endpoint_text":"- Duration of severe hypogammaglobulinemia in patients with such complication","definition_or_measurement_approach":"Measured duration of severe hypogammaglobulinemia (as defined in protocol) in affected patients over study follow-up."}
• {"endpoint_text":"- Number of patients developing a severe hypogammaglobulinemia (gammaglobulin level < 4 g/dl) in both arms at W12, W24, W36, W52, W78, W104","definition_or_measurement_approach":"Number and proportion of patients with gammaglobulin level < 4 g/dL assessed at Weeks 12, 24, 36, 52, 78 and 104."}
• {"endpoint_text":"- Variation in gammaglobulin classes and subclass levels throughout the study (W0, W12, W24, W36, W52, W78, W104)","definition_or_measurement_approach":"Changes from baseline in gammaglobulin classes and subclasses measured at specified weeks (W0, W12, W24, W36, W52, W78, W104)."}
• {"endpoint_text":"- Number of severe infections requiring hospitalization during the study","definition_or_measurement_approach":"Count of severe infections (requiring hospitalization) occurring during study period."}
• {"endpoint_text":"- Number of haemorrhagic events evaluated by the Khellaf Score at W6, W12, W24, W36, W52, W78, W104.","definition_or_measurement_approach":"Number and proportion of haemorrhagic events scored using the Khellaf Score at specified weeks."}
• {"endpoint_text":"- Platelet levels at W6, W12, W 24, W36, W52, W78, W104","definition_or_measurement_approach":"Laboratory platelet counts measured at Weeks 6, 12, 24, 36, 52, 78 and 104."}
• {"endpoint_text":"- Use of the SF-36 health questionnaire and FACIT-Fatigue scale (Functional assessment of chronic illness therapy) to assess patient’s quality of life at inclusion, W12, W24 and W52","definition_or_measurement_approach":"Patient-reported quality of life assessed using SF-36 and FACIT-Fatigue at baseline and Weeks 12, 24 and 52."}
• {"endpoint_text":"- Percentage of each B-cell subpopulation, T Follicular helper population and levels of cytokines (including BAFF) and anti-platelet antibodies at W12, W24, W36, W52, W78, W104.","definition_or_measurement_approach":"Laboratory immunophenotyping and cytokine/antibody level assessments at listed timepoints (W12, W24, W36, W52, W78, W104)."}

France

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

512

Number Of Sites

38

Number Of Participants

132

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Glaxosmithkline Research & Development Limited","duties_or_roles":"Research grant: funded by GSK","organisation_type":""}