Adult patients with non-infectious active cryoglobulinemia vasculitis. MedDRA version: 20.0 Level: LLT Classification code 10075624 Term: Cryoglobulinaemic vasculitis System Organ Class: 100000004866 MedDRA version: 21.0 Level: LLT Classification code 10075623 Term: Cryoglobulinemic vasculitis System Organ Class: 100000004866
Conditions
Interventions
Trade Name: BENLYSTA®
Pharmaceutical Form: Solution for injection
INN or Proposed INN: BELIMUMAB
CAS Number: 356547-88-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration num
Sponsors
Assistance Publique - Hôpitaux de Paris / DRCI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age > 18 years • Written inform consent • Active cryoglobulinemia vasculitis define by 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), and history of positive cryoglobulinemia • 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 1x109/L Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: • Patient with a vasculitis unrelated to cryoglobulinemia • Patient with non active cryoglobulinemia vasculitis, • Excluded concomitant medications: > 365 days Prior to Belimumab: o 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: o Intravenous cyclophosphamide > 30 Days Prior to Belimumab (or 5 half lives, whichever is greater) o 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, other than carcinoma in situ of the cervix or excised basal cell, squamous cell carcinoma of the skin or hemopathy • 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 significant IgG deficiency (IgG level 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, an tivirals, anti-fungals, or anti parasitic agents) within 60 days of the inclusion visi. • 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 • 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, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy of belimumab compared to placebo in patients with non-infectious active cryoglobulinemia vasculitis.;Secondary Objective: • Safety and tolerability of treatments as assessed by frequency and severity of adverse clinical events • Complete, partial (improvement in some but not all organs involved at baseline) and non clinical (no clinical improvement) response rate • Rate of complete renal response • Rate of cryoglobulinemia clearance • Rate of negativation of rheumatoid factor activity • Rate of normalization of C4 complement level • Early failure rate at W4 (non clinical response at W4) • Clinical relapse rate and the time to relapse between the two treatments groups, • Cumulative dose of corticosteroids received between the two treatments groups, • Evolution of gammaglobulin and of CD19+ B cells levels • Quality of life scores (SF-36) between the two treatment groups, • Rate of infections (severe or not) and other complications (lymphoma) • BVAS activity score • Immunomonitoring (deep immunophenotyping, and cytokines production);Primary end point(s): Complete clinical response rate of vasculitis symptoms at W25 with corticosteroid withdrawal (prednisone at 0 mg/day) at week (W) 12.;Timepoint(s) of evaluation of this end point: W25 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety and tolerability of treatments as assessed by frequency and severity of adverse clinical events from baseline to W25 and at W48 - Complete, partial and non clinical response rate at W13, W25 and at W48. - Complete renal response rate at W13, W25 and W48 defined by : proteinuria 60 ml/min/1.73 m². - Rate of cryoglobulinemia clearance, negativation of rheumatoid factor activity and of normalization of C4 complement level at W13, W25 and at W48, - Rate of early failures (non clinical response at W5), - Clinical relapse rate defined by de novo appearance or recurrence of a manifestation attributable to cryoglobulinemia vasculitis during 48 weeks of follow-up, - Rate and time to relapse from baseline to W48 - Cumulative dose of prednisone at W25 and at W48, - Evolution of gammaglobulin and of CD19+ B levels from baseline to W48 - Quality of life score SF-36 at baseline, W25 and W48, - Rate of infections (severe or not) and other complications during the 48 weeks of follow-up - BVAS activity score at baseline, W13, W25 and W48.;Timepoint(s) of evaluation of this end point: Baseline, W13, W25 and W48. | — |
Countries
France
Contacts
Public ContactChef de projet
Assistance Publique - Hôpitaux de Paris / DRCI
Outcome results
None listed