BELIMUMAB for Cryoglobulinemia vasculitis|Mixed cryoglobulinemia-associated vasculitis

Inclusion criteria

• {"criterion_text":"- 1.\tAge ≥ 18 years\n- 2.\tWritten inform consent\n- 3.\tActive mixed cryoglobulinemia vasculitis, at initiation of rituximab, define by a.\ta clinically active vasculitis with skin, joint, renal, peripheral nerve, central neurological, digestive, pulmonary and/or cardiac involvement, b.\tand history of positive cryoglobulinemia and/or positive Rheumatoid factor associated with low C4 complement level , and/or a monoclonal component (IgM Kappa) and/or a histologal proof of vasculitis in the affected organs\n- 4.\tAffiliated to National French social security system\n- 5.\tHaving received Rituximab as induction therapy within 6 weeks (1 to 4 infusions, dose at the discretion of the investigator)\n- 6.\tFemale subjects of childbearing potential must have a negative serum or urinary pregnancy test at inclusion visit, and confirmed monthly while in study, out to at least 92 days (5 half lives) post last dose.\n- 7.\tFor subjects with reproductive potential (male or female), a willingness to use contraceptive measures adequate to prevent the subject or the subject’s partner from becoming pregnant during the study from 2 weeks prior to administration of the 1st dose of study agent until 92 days after the last dose of study agent. Therefore the subjects agree to 1 of the following: a.\tComplete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent until 92 days after the last dose of study agent (Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception) or b.\tConsistent and correct use of 1 of the following acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 92 days after the last dose of study agent o\tOral contraceptive, either combined or progestogen alone o\tInjectable progestogen o\tImplants of levonorgestrel or etonogestrel o\tEstrogenic vaginal ring o\tPercutaneous contraceptive patches o\tIntrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label o\tMale partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, “documented” refers to the outcome of the investigator's/designee’s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records o\tDouble barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring subjects understand how to properly use these methods of contraception.\n- 8.\tHIV negative serology ; negative HBs Ag test and HBc Ab test; HCV negative serology or negative HCV RNA if positive HCV serology within 3 months before inclusion: - In case of negative AgHBs and positive HBc Ab test, HBV DNA test must be negative; AND Hepatitis B surveillance should be started (monthly HBsAg and HBV DNA testing for the duration of the study treatment and at least every 12 weeks after treatment is discontinued for the duration of study treatment. In addition, antiviral prophylaxis should be started before the first administration of the study treatment and continued until 12 months after completion of study treatment.\n- 9.\tNeutrophils (ANC) >1x109/L,"}

Exclusion criteria

• {"criterion_text":"- 1.\tPatient with a vasculitis unrelated to cryoglobulinemia\n- 10.\tHave current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior the inclusion visit\n- 11.\tHave a historically positive HIV test according to results obtained within 3 months prior to inclusion visit\n- 12.\tHepatitis status according to results obtained within 3 months prior to inclusion visit: a.\tPositive test for hepatitis B RNA b.\tPositive test for Hepatitis C RNA\n- 13.\tHave a history of a hypersensitivity or an anaphylactic reaction to parenteral administration of Belimumab, corticosteroids or any excipients of the treatments administered during the study\n- 14.\tIf Women of Child Bearing Potential (WCBP) are included please see special instructions in Inclusion criteria\n- 15.\tPregnant or breast feeding women\n- 16.\tHave any intercurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study\n- 17.\tPatients under legal protection or unable to consent\n- 18.\tParticipation to another interventional study\n- 2.\tPatient with non active cryoglobulinemia vasculitis, at initiation of rituximab. Patients with mixed inactive vasculitis following rituximab administration may be included.\n- 3.\tExcluded concomitant medications a.\t365 days Prior to Investigational Medicinal Product (Belimumab or placebo) ):c.\tIntravenous cyclophosphamide 30 Days Prior to Investigational Medicinal Product (Belimumab or placebo): (or 5 half lives, whichever is greater) o\tAny non-biologic investigational agent (Investigational agent applies to any drug not approved for sale in the country in which it being use) d.\tLive vaccines within 30 days prior to baseline or concurrently with Investigational Medicinal Product (Belimumab or placebo): o\tAny biologic investigational agent (e.g., abetimus sodium, anti CD40L antibody, BG9588/ IDEC 131) \tInvestigational agent applies to any drug not approved for sale in the country in which it is being used b.\t180 Days Prior to Investigational Medicinal Product (Belimumab or placebo)\n- 4.\tHave a history of malignant neoplasm within the last 5 years, other than carcinoma in situ of the cervix or excised basal cell, squamous cell carcinoma of the skin and low-grade hemopathy with no indication for a specific treatment\n- 5.\tHave a Progressive multifocal leukoencephalopathy\n- 6.\tHave evidence of serious suicide risk including any history of suicidal behaviour 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- 7.\tHave a history of a primary immunodeficiency\n- 8.\tHave a history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant.\n- 9.\tInfection history: a.\tCurrently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus,) b.\tInfection requiring hospitalization and/or use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 60 days of the inclusion visit."}

Primary endpoints

• {"endpoint_text":"- Complete clinical response rate of vasculitis symptoms at week (W) 25 with oral corticosteroid withdrawal (prednisone (or prednisolone, only if prednisone is out of stock in the market) at 0 mg/day) at week (W) 12.","definition_or_measurement_approach":"Measured as the complete clinical response rate of vasculitis symptoms at Week 25, with oral corticosteroid withdrawal to 0 mg/day at Week 12."}

Secondary endpoints

• {"endpoint_text":"- •Safety and tolerability of treatments as assessed by frequency and severity of adverse clinical events at W25 and at W48\n- •Complete, partial and non-clinical response rate at W13, W25 and at W48.\n- •Complete renal response rate at W13, W25 and W48\n- •Rate of cryoglobulinemia clearance, of negativation of rheumatoid factor activity and of normalization of C4 complement level at W13, W25 and at W48\n- •Rate of early failures (non clinical response at W5)","definition_or_measurement_approach":"Safety/tolerability: frequency and severity of adverse clinical events assessed at W25 and W48. Response rates (complete/partial/non-clinical) assessed at W13, W25, W48. Renal response assessed at W13, W25, W48. Cryoglobulinemia clearance, RF negativation, C4 normalization assessed at W13, W25, W48. Early failure defined as non-clinical response at Week 5."}

France

Earliest CTIS Part Ii Submission Date

12-11-2024

Latest Decision Or Authorization Date

20-11-2024

Processing Time Days

8

Number Of Sites

3

Number Of Participants

52

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France