Type I cryoglobulinemia MedDRA version: 21.1 Level: LLT Classification code 10011475 Term: Cryoglobulinemia System Organ Class: 100000004866
Conditions
Interventions
Trade Name: SARCLISA 500 mg
Product Name: Isatuximab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Isatuximab
Other descriptive name: SAR650984
Concentration unit: mg milligram(s)
Co
Sponsors
Assistance Publique - Hôpitaux de Paris / DRCI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age > 18 years • Written informed consent • Indolent Multiple myeloma or monoclonal gammopathy of unknown significance (MGUS) with monoclonal IgG component • Active cryoglobulinemia vasculitis defined by positive type I IgG cryoglobulinemia and a clinically active cryoglobulinemia with skin, joint, renal, and/or peripheral involvement, • Treated naïve or relapsers type I cryoglobulinemia patients • Affiliated to National French social security system • Contraception : a) Male participants : A male participant must agree to use a highly effective method of contraception during the participation period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period. b) Female participants : A female participant is eligible to participate if she is not pregnant, not breastfeeding, and with at least one of the following conditions: ?Not a female of childbearing potential (FCBP), OR ?A FCBP who must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 24 hours of starting study medication and must apply a highly effective method of contraception during the participation period and for at least 7 months after the last dose of study treatment and refrain from donating oocyte during this period • HIV negative serology; negative HBs Ag test; HCV negative serology and/or negative HCV RNA if positive HCV serology 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 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Patient with a vasculitis unrelated to cryoglobulinemia • Patient with non-active cryoglobulinemia vasculitis, • Patient with diagnosis of multiple myeloma • Patient treated with immunosuppressant (e.g alkylating agent, Rituximab, chemotherapy for plasma-cell neoplasms) introduced or increased in the month prior to the inclusion, • Live vaccines within 30 days prior to baseline or concurrently with Isatuximab • 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. • Active tuberculosis • HIV positive, positive Ag HbS, positive HCV RNA • Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results. • Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents. • Hypersensitivity to the active substances (isatuximab and premedication) or to any of their excipients • Received any investigational drug within 14 days prior to inclusion or within 5 half-lives of the investigational drug, whichever is longer. • Participation in another interventional study or being in the exclusion period at the end of a previous study. • Vulnerable populations (e.g. pregnant or breastfeeding women) • Neutrophils < 1000/mm3 • Platelets < 75000/mm3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the complete clinical response rate of Isatuximab in type I IgG cryoglobulinemia;Secondary Objective: • Safety and tolerability of treatment as assessed by frequency and severity of adverse clinical events • Early complete response rate at W12 • Complete, partial (improvement in some but not all organs involved at baseline) and non clinical (no clinical improvement) response rate at W12 and W20 • 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, • Course of plasma cell associated disorder • Evolution of gammaglobulin and of CD19+ B cells levels • Quality of life scores (SF-36) (Appendix 1), • Rate of infections (severe or not) and other complications • Birmingham Vasculitis Activity Score (BVAS) (Appendix 2) • Immunomonitoring (deep immunophenotyping, cytokines production, spectrometry, Fish analysis, single plasma cell repertoire) ;Primary end point(s): Complete clinical response rate of cryoglobulinemia vasculitis symptoms at week (W) 20;Timepoint(s) of evaluation of this end point: Week 20 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety and tolerability of treatment as assessed by frequency and severity of adverse clinical events at W20 • Complete, partial and non-clinical response rate at W12, and at W20. • Rate of cryoglobulinemia clearance, of negativation of rheumatoid factor activity and of normalization of C4 complement level at W12, and at W20. • Rate of early failures (non-clinical response at W4), • Rate of renal complete remission defined as proteinuria <0.5g/24h or proteinuria/creatininuria <50 mg/mmol, disappearance of hematuria, and glomerular filtration rate =60ml/min/1.73m² at W12, and at W20. • Clinical relapse rate defined by de novo appearance or reappearance of a manifestation attributable to cryoglobulinemia vasculitis during 48 weeks of follow-up, • Rate and time to relapse from baseline to W48 • Course of plasma cell associated disorder W12, and at W20. • Mean change of gammaglobulin and CD19+ B cells levels from baseline to W20 • Quality of life score SF-36 at baseline, and W20, • Rate of infections (severe or not) and other complications during the 48 weeks of follow-up • BVAS activity score at baseline, W12, and W20. • Immunomonitoring (deep immunophenotyping, cytokines production, spectrometry, Fish analysis, single plasma cell repertoire) at baseline, week 12, and week 20 ;Timepoint(s) of evaluation of this end point: baseline, week 12, and week 20 | — |
Countries
France
Contacts
Public ContactElodie SOLER
Assistance Publique - Hôpitaux de Paris / DRCI
Outcome results
None listed