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Cryoglobulinemia vasculitis (CV) is a systemic immune-mediated small vessel vasculitis. Rituximab proved effective on main vasculitis signs, with a complete clinical response of 65%. However, CV relapse is noted in up to 40% of patients. Following rituximab, serum Blys concentration significantly increased and may favor relapses. Tribeca is a multicentre randomized controled study comparing safety and efficacy of belimumab to placebo in non infectious cryoglobulinemia vasculitis.
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Inclusion and exclusion criteria
Inclusion Criteria:
The eligibility criteria will be checked at the inclusion/randomization visit. Patients meeting the following criteria may be included in the study:
Age > 18 years
Written inform consent
Active mixed cryoglobulinemia vasculitis, at initiation of rituximab, define by a. a clinically active vasculitis with skin, joint, renal, peripheral nerve, central neurological, digestive, pulmonary and/or cardiac involvement , b. 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
Affiliated to National French social security system
Having received Rituximab as induction therapy within 6 weeks (1 to 4 infusions, dose at the discretion of the investigator)
Female 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.
For 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:
Complete 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
Consistent 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 Oral contraceptive, either combined or progestogen alone o Injectable progestogen o Implants of levonorgestrel or etonogestrel o Estrogenic vaginal ring o Percutaneous contraceptive patches o Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label
o Male 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
HIV 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:
o 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; HCV negative serology or negative HCV RNA if positive HCV serology within 3 months before inclusion
neutrophils (ANC) >1x109/L
Exclusion criteria :
Subjects will be not included from the study if they meet any of the following criteria:
Patient with a vasculitis unrelated to cryoglobulinemia
Patient with non active cryoglobulinemia vasculitis, at initiation of rituximab. Patients with mixed inactive vasculitis following rituximab administration may be included.
Excluded concomitant medications:
Have 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
Have 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
Have a Progressive multifocal leukoencephalopathy
Have a history of a primary immunodeficiency
Have a history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant
Infection history:
Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus
Infection 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.
Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior to the inclusion visit
Have a historically positive HIV test according to results obtained within 3 months prior to inclusion visit
Hepatitis status according to results obtained within 3 month prior to inclusion visit :
Positive test for hepatitis B RNA
Positive test for Hepatitis C RNA
Have 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
If Women of Child Bearing Potential (WCBP) are included please see special instructions in Inclusion criteria
Pregnant or breast feeding women
Have any intercurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study
Patients under legal protection or unable to consent
Participation to another interventional study
Primary purpose
Allocation
Interventional model
Masking
48 participants in 2 patient groups, including a placebo group
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Central trial contact
David Saadoun, MD PhD; Jérôme Lambert, MD PhD
Data sourced from clinicaltrials.gov
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