ISATUXIMAB for Relapsed/refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"- Participants must have a documented diagnosis of multiple myeloma (MM)\n- -Participants with measurable disease defined as at least one of the following: -Serum M-protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or; --Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or; --Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).\n- -Participant with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy.\n- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either is not a female of childbearing potential (FCBP) or agrees to practice complete abstinence or use approved contraception methods.\n- Male participants agree to practice true abstinence or agree to use approved contraception methods while receiving study treatment, during dose interruptions and at least 5 months following study treatment discontinuation, even if has undergone a successful vasectomy.\n- Capable of giving signed informed consent."}

Exclusion criteria

• {"criterion_text":"- -Primary refractory MM defined as participants who have never achieved at least a minimal response (MR) with any treatment during the disease course\n- -Participants with prior anti-CD38 treatment if: a) administered <9 months before first isatuximab administration or randomization as applicable or, b) Intolerant to the anti- CD38 previously received\n- -Prior treatment with carfilzomib\n- -Known history of allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib), prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), polysorbate 80, or any of the components (active substance or excipient) of study treatment that are not amenable to premedication with steroids, or intolerance to arginine and Poloxamer 188 that would prohibit further treatment with these agents\n- -Uncontrolled or active infection with hepatitis A, B, and C virus; known acquired immunodeficiency syndrome (AIDS)-related illness; active primary amyloid light chain (AL) amyloidosis\n- -Any severe acute or chronic medical condition which could impair the ability of the participant to participate in the study or interfere with interpretation of study results (eg, systemic infection unless specific anti-infective therapy is employed) or participant unable to comply with the study procedures."}

Primary endpoints

• {"endpoint_text":"- Overall response rate (ORR) – Cohorts 1 to 3","definition_or_measurement_approach":""}
• {"endpoint_text":"- Maximum observed concentration (Cmax) over Cycle 1- Cohorts 4 to 5","definition_or_measurement_approach":"Cmax measured as maximum observed plasma concentration during Cycle 1 (pharmacokinetic measurement)."}
• {"endpoint_text":"- Cumulative area under the curve over the first 4 weeks (AUC4weeks) of isatuximab treatment- Cohorts 4 to 5","definition_or_measurement_approach":"AUC over the first 4 weeks of isatuximab dosing (pharmacokinetic measurement)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6","definition_or_measurement_approach":"Measured by patient preference questionnaire at Day 15 of Cycle 6 (PEQ/PESQ instruments)."}
• {"endpoint_text":"- Incidence rate of infusion reactions (IRs)","definition_or_measurement_approach":"Incidence rate measured as number/proportion of participants experiencing infusion reactions during study treatment."}
• {"endpoint_text":"- Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters","definition_or_measurement_approach":"Safety assessed by counting participants with TEAEs/SAEs and evaluating laboratory parameter changes."}
• {"endpoint_text":"- Incidence rate of injection site reactions (ISRs)","definition_or_measurement_approach":"Incidence of injection site reactions recorded during subcutaneous administration."}
• {"endpoint_text":"- PK concentration: trough plasma concentration (Ctrough)","definition_or_measurement_approach":"Trough plasma concentration measured pre-dose at specified timepoints."}
• {"endpoint_text":"- Overall response rate (ORR)","definition_or_measurement_approach":"Overall response rate assessed using standard multiple myeloma response criteria (not further specified in available data)."}
• {"endpoint_text":"- Duration of response (DOR)","definition_or_measurement_approach":"Time from first documented response to progression or death."}
• {"endpoint_text":"- Time to first response (TT1R)","definition_or_measurement_approach":"Time from first dose to first documented response."}
• {"endpoint_text":"- Time to best response (TTBR)","definition_or_measurement_approach":"Time from first dose to best observed response."}
• {"endpoint_text":"- Progression free survival (PFS)","definition_or_measurement_approach":"Time from randomization/enrollment to disease progression or death."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Time from randomization/enrollment to death from any cause."}
• {"endpoint_text":"- Incidence of participants with anti-drug antibodies (ADA) against isatuximab","definition_or_measurement_approach":"Measured by laboratory ADA assays; incidence of participants developing anti-isatuximab antibodies."}
• {"endpoint_text":"- Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously","definition_or_measurement_approach":"Patient-reported expectations assessed with PEQ-BL v2 at baseline."}
• {"endpoint_text":"- Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously","definition_or_measurement_approach":"Patient-reported experience and satisfaction measured using PESQ v2."}
• {"endpoint_text":"- Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ)","definition_or_measurement_approach":"Health state utility measured via HRUPQ instrument."}
• {"endpoint_text":"- Health Related Quality of Life (HRQL)","definition_or_measurement_approach":"HRQL measured by specified validated instruments (not fully detailed in available data)."}
• {"endpoint_text":"- European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)","definition_or_measurement_approach":"EQ-5D-5L administered to assess generic health status."}

Greece

Earliest CTIS Part Ii Submission Date

12-04-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

696

Number Of Sites

2

Number Of Participants

22

Portugal

Earliest CTIS Part Ii Submission Date

12-04-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

696

Number Of Sites

3

Number Of Participants

5

Czechia

Earliest CTIS Part Ii Submission Date

12-04-2024

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

693

Number Of Sites

4

Number Of Participants

28

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

codes: 1,2

Name

Labcorp Early Development Laboratories Limited

Responsibilities

code: 4

Name

Labcorp Central Laboratory Services LP

Responsibilities

code: 4

Third parties

• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"eCOA (Clinical Outcomes Assessment Instrument)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"24 Hour Emergency Services","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"codes: 1,2","organisation_type":"Pharmaceutical company"}
• {"country":"Portugal","full_name":"Evidenze Portugal Unipessoal Lda.","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"Local laboratory (Hematology & Biochemistry tests,Imaging exams and cardiological exams_ECG-Triplex)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Independent Review Committee (Imaging)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpoint Communications Inc.","duties_or_roles":"Training Development","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Mapi Research Trust","duties_or_roles":"Translations","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code: 3","organisation_type":"Pharmaceutical company"}