Multicenter Randomized Double-blind Study Comparing the Efficacy and Safety of Belimumab in the Treatment of Non-infectious Active Cryoglobulinemia Vasculitis Compared to Placebo. TRIBECA STUDY (Treatment nd BElimumab in Cryoglobulinemia Associated

• Status: Not yet recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Belimumab

Criteria

Inclusion Criteria:

• Age > 18 years

• Written inform consent

• Active cryoglobulinemia vasculitis define by positive cryoglobulinemia and a clinically active vasculitis with skin, joint, renal, peripheral nerve, central neurological, digestive, pulmonary and/or cardiac involvement (no histological evidence needed if presence of purpura demonstrated),

• Affiliated to National French social security system

• Having received Rituximab as induction therapy within 6 weeks

• 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%.

Therefore, these women must have a negative serum pregnancy test at screening, and confirmed monthly while in study, out to at least 4 months (5 half lives) 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 (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 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 rate as 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 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

• Double 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.

• HIV negative serology ; negative HBs Ag test and HBc Ab test; HCV negative serology or negative HCV RNA if positive HCV serology

• Adequate haematological status:

• neutrophils (ANC) >1x109/L;

Exclusion Criteria:

• Patient with a vasculitis unrelated to cryoglobulinemia

• Patient with non active cryoglobulinemia vasculitis,

• Patient with immunosuppressant introduced or increased in the month prior to the inclusion, (except Rituximab)

• Patients receiving corticosteroid therapy > 0.5 mg/kg/d > 1 month before the inclusion or > 1 mg/kg/d >2 weeks before inclusion or taking more than 3000 mg methylprednisolone 4 weeks prior to the inclusion visit

• Excluded concomitant medications (except Rituximab) :

• 365 days Prior to Belimumab:

• Any biologic investigational agent (e.g., abetimus sodium, anti CD40L antibody, BG9588/ IDEC 131)

• Investigational agent applies to any drug not approved for sale in the country in which it is being used

• 180 Days Prior to Belimumab:

• Intravenous cyclophosphamide

• If concomitant use with cyclophosphamide, enhanced safety monitoring required.

• Serum IgG levels should be measured monthly in this situation

• Benlysta should be discontinued in subjects with serum IgG levels <250 mg/dL associated with a severe or serious infection

• 30 Days Prior to Belimumab (or 7 half lives, whichever is greater)

• Any non-biologic investigational agent

• Investigational agent applies to any drug not approved for sale in the country in which it is being use

• Live vaccines within 30 days prior to baseline or concurrently with belimumab

• Have a history of malignant neoplasm within the last 5 years

• Have a Progressive multifocal leukoencephalopathy

• .

• 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 history of a primary immunodeficiency

• Have a significant IgG deficiency (IgG level < 400 mg/dL)

• Have a history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant.

• • Have an IgA deficiency (IgA level < 10 mg/dL

• 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 Day 0.

• Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior to Day 0

• Have a historically positive HIV test or test positive at screening for HIV

• Hepatitis status:

• Serologic evidence of current or past Hepatitis B (HB) infection based on the results of testing for HBsAg and HBcAb as follows:

• Patients positive for HBsAg or HBcAb are excluded

• Positive test for Hepatitis C RNA

• Have a history of a hypersensitivity or an anaphylactic reaction to parenteral administration of Belimumab or Rituximab, corticosteroids or any excipients of the treatments administered during the study

• If Women of Child Bearing Potential (WCBP) are included please see special instructions above

• 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