A Randomized, Phase 2, Open Label Study Evaluating Subcutaneous Administration of Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM)
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Sanofi
- Enrollment
- 118
- Locations
- 23
- Primary Endpoint
- Overall response rate (ORR) - Cohorts 1 to 3
Study Overview
Brief Summary
The main purpose of this study is to measure the efficacy (Myeloma response) of subcutaneous (SC) isatuximab treatment in combination with carfilzomib and dexamethasone in adult participants with RRMM having received 1 to 3 prior lines of therapy, and to characterize the PK of isatuximab in combination with carfilzomib and dexamethasone after manual and On Body Delivery System (OBDS) administration. After confirmation of the feasibility of SC isatuximab by manual administration, patient will be randomized to 1 of the 2 delivery methods of SC isatuximab.
Detailed Description
The duration of the study for a participant will include a period for screening of up to 28 days. A cycle duration is 28 days. Participants will be allowed to continue therapy until disease progression, unacceptable adverse events (AEs), participant request to discontinue treatment, or any other reason, as well as the study treatment is commercially available and reimbursed in the participant's country, or is available from another source, whichever is first. The overall study duration will be of approximately 45 months.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants must have a documented diagnosis of multiple myeloma (MM)
- •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).
- •Participant with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy.
- •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.
- •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.
- •Capable of giving signed informed consent.
Exclusion Criteria
- •Primary refractory MM defined as participants who have never achieved at least a minimal response (MR) with any treatment during the disease course
- •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
- •Prior treatment with carfilzomib
- •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
- •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
- •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.
- •The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Arms & Interventions
Cohort 1: manual administration
Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Isatuximab (Drug)
Cohort 1: manual administration
Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Carfilzomib (Drug)
Cohort 1: manual administration
Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone (Drug)
Cohort 1: manual administration
Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone IV (Drug)
Cohort 1: manual administration
Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Montelukast (Drug)
Cohort 1: manual administration
Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Acetaminophen (Drug)
Cohort 1: manual administration
Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Diphenhydramine (Drug)
Cohort 1: manual administration
Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Methylprednisolone (Drug)
Part 1 Cohort 2: manual administration
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Isatuximab (Drug)
Part 1 Cohort 2: manual administration
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Carfilzomib (Drug)
Part 1 Cohort 2: manual administration
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone (Drug)
Part 1 Cohort 2: manual administration
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone IV (Drug)
Part 1 Cohort 2: manual administration
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Montelukast (Drug)
Part 1 Cohort 2: manual administration
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Acetaminophen (Drug)
Part 1 Cohort 2: manual administration
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Diphenhydramine (Drug)
Part 1 Cohort 2: manual administration
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.
Intervention: Methylprednisolone (Drug)
Part 2 Cohort 3 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Isatuximab (Drug)
Part 2 Cohort 3 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Carfilzomib (Drug)
Part 2 Cohort 3 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone (Drug)
Part 2 Cohort 3 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone IV (Drug)
Part 2 Cohort 3 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Montelukast (Drug)
Part 2 Cohort 3 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Acetaminophen (Drug)
Part 2 Cohort 3 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Diphenhydramine (Drug)
Part 2 Cohort 3 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Methylprednisolone (Drug)
Part 2 Cohort 3 Randomized Cohort: Manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Isatuximab (Drug)
Part 2 Cohort 3 Randomized Cohort: Manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Carfilzomib (Drug)
Part 2 Cohort 3 Randomized Cohort: Manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone (Drug)
Part 2 Cohort 3 Randomized Cohort: Manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone IV (Drug)
Part 2 Cohort 3 Randomized Cohort: Manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Montelukast (Drug)
Part 2 Cohort 3 Randomized Cohort: Manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Acetaminophen (Drug)
Part 2 Cohort 3 Randomized Cohort: Manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Diphenhydramine (Drug)
Part 2 Cohort 3 Randomized Cohort: Manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Methylprednisolone (Drug)
Part 3 Cohort 4 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Isatuximab (Drug)
Part 3 Cohort 4 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Carfilzomib (Drug)
Part 3 Cohort 4 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone (Drug)
Part 3 Cohort 4 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone IV (Drug)
Part 3 Cohort 4 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Montelukast (Drug)
Part 3 Cohort 4 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Acetaminophen (Drug)
Part 3 Cohort 4 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Diphenhydramine (Drug)
Part 3 Cohort 4 Randomized Cohort: OBDS to manual
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Methylprednisolone (Drug)
Part 3 Cohort 4: Randomized Cohort: manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Isatuximab (Drug)
Part 3 Cohort 4: Randomized Cohort: manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Carfilzomib (Drug)
Part 3 Cohort 4: Randomized Cohort: manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone (Drug)
Part 3 Cohort 4: Randomized Cohort: manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone IV (Drug)
Part 3 Cohort 4: Randomized Cohort: manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Montelukast (Drug)
Part 3 Cohort 4: Randomized Cohort: manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Acetaminophen (Drug)
Part 3 Cohort 4: Randomized Cohort: manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Diphenhydramine (Drug)
Part 3 Cohort 4: Randomized Cohort: manual to OBDS
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Methylprednisolone (Drug)
Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Isatuximab (Drug)
Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Carfilzomib (Drug)
Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone (Drug)
Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone IV (Drug)
Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Montelukast (Drug)
Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Acetaminophen (Drug)
Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Diphenhydramine (Drug)
Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Methylprednisolone (Drug)
Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Isatuximab (Drug)
Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Carfilzomib (Drug)
Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone (Drug)
Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Dexamethasone IV (Drug)
Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Montelukast (Drug)
Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Acetaminophen (Drug)
Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Diphenhydramine (Drug)
Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants
Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.
Intervention: Methylprednisolone (Drug)
Outcomes
Primary Outcomes
Overall response rate (ORR) - Cohorts 1 to 3
Time Frame: 6 months after the Last Participant In (LPI) i.e., approximately 16 months
ORR defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria assessed by Independent Review Committee (IRC).
Maximum observed concentration (Cmax) over Cycle 1- Cohorts 4 to 5
Time Frame: Cycle 1 (28 days)
Cumulative area under the curve over the first 4 weeks (AUC4weeks) of isatuximab treatment- Cohorts 4 to 5
Time Frame: Cycle 1 (28 days)
Secondary Outcomes
- Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6(6 months from LPI i.e., approximately 16 months)
- Incidence rate of infusion reactions (IRs)(From the signing of the informed consent to 30 days following the last administration of any study treatment i.e., up to approximately 45 months)
- Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters(From the signing of the informed consent to 30 days following the last administration of any study treatment i.e., up to approximately 45 months)
- Incidence rate of injection site reactions (ISRs)(18 months after LPI i.e., approximately 28 months)
- PK concentration: trough plasma concentration (Ctrough)(Cycle 2 Day 1 and Cycle 6 Day 1 (1 Cycle = 28 days))
- Overall response rate (ORR)(6 months after the Last Participant In (LPI) i.e., approximately 16 months)
- Duration of response (DOR)(6 months after the Last Participant In (LPI) i.e., approximately 16 months)
- Time to first response (TT1R)(6 months after the Last Participant In (LPI) i.e., approximately 16 months)
- Time to best response (TTBR)(6 months after the Last Participant In (LPI) i.e., approximately 16 months)
- Progression free survival (PFS)(18 months after LPI i.e., approximately 28 months)
- Overall survival (OS)(18 months after LPI i.e., approximately 28 months)
- Incidence of participants with anti-drug antibodies (ADA) against isatuximab(From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e., approximately 13 months (1 Cycle = 28 days))
- Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously(Baseline)
- Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously(18 months after LPI i.e., approximately 28 months)
- Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ)(18 months after LPI i.e., approximately 28 months)
- Health Related Quality of Life (HRQL)(18 months after LPI i.e., approximately 28 months)
- European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)(18 months after LPI i.e., approximately 28 months)