Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
- Conditions
- Multiple Myeloma
- Interventions
- Device: Investigational injector device
- Registration Number
- NCT04045795
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objectives:
* To evaluate the safety and tolerability of isatuximab administered subcutaneously (SC) versus intravenously (IV)
* To assess the safety and tolerability (including local injection site tolerability) of isatuximab using the (investigational) isatuximab injector device
* To evaluate the pharmacokinetics (PK) of SC and IV isatuximab
Secondary Objectives:
* To estimate absolute bioavailability of SC and IV isatuximab
* To measure receptor occupancy (RO) after isatuximab SC versus IV administration
* To assess efficacy of isatuximab after SC and IV administration
* To assess patient expectations prior to and patient experience and satisfaction after SC administration
* To evaluate potential immunogenicity of SC or IV isatuximab
- Detailed Description
Total study duration is variable depending on treatment and follow-up periods, including 21 days of screening, and treatment period until disease progression, unacceptable adverse reaction or other reason for discontinuation. End of treatment will be 30 days after last administration of investigational medicinal product, or before further anti-myeloma therapy, whichever comes first; approximately 14 months after first study treatment administration.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose regimen 1 isatuximab SAR650984 SC Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 3 Investigational injector device Isatuximab SC administration dose level 3 using the investigational injector device once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 4 isatuximab SAR650984 IV Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 5 dexamethasone Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 3 isatuximab SAR650984 SC Isatuximab SC administration dose level 3 using the investigational injector device once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 5 pomalidomide Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 2 isatuximab SAR650984 SC Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 5 isatuximab SAR650984 IV Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 1 pomalidomide Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 1 dexamethasone Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 2 pomalidomide Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 2 dexamethasone Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 3 dexamethasone Isatuximab SC administration dose level 3 using the investigational injector device once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 3 pomalidomide Isatuximab SC administration dose level 3 using the investigational injector device once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 4 dexamethasone Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle Dose regimen 4 pomalidomide Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
- Primary Outcome Measures
Name Time Method PK assessment: Ctrough Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Concentration observed just before treatment administration during repeated dosing (Ctrough)
PK assessment: AUClast Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast) (AUClast)
Assessment of adverse events (AEs) Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration) Number of participants with adverse events
PK assessment: Clast Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Last concentration observed above the lower limit of quantification after the first infusion (Clast)
Pharmacokinetic (PK) assessment: Ceoi Baseline to end of treatment (EOT) after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Concentration observed at the end of infusion (Ceoi)
PK assessment: Cmax Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Maximum concentration observed after the first infusion (Cmax)
PK assessment: tlast Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Time of Clast (tlast)
PK assessment: AUC0 T Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Area under the plasma concentration versus time curve calculated over the dosing interval T (168h or 336h) (AUC0 T)
PK assessment: tmax Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Time to reach Cmax (tmax)
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) ORR is the proportion of patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) using the IMWG response criteria
Duration of response (DOR) From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) Time from the date of the first response to the date of first progressive disease (PD) or death, whichever happens first
Time to response (TTR) From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) Time from the date of first study treatment to the first response
Immunogenicity: Anti drug antibody levels Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) Incidence of patients with anti drug antibodies against isatuximab
Estimation of absolute bioavailability of isatuximab Day 8 Absolute bioavailability of isatuximab SC, expressed as a percentage, estimated from AUC0-168h obtained after intravenous (IV) and extravascular (EV) administration
Clinical benefit rate (CBR) From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) Proportion of patients with sCR, CR, VGPR, PR or minimal response (MR) according to IMWG criteria
Time to progression (TTP) From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) Time from date of first study treatment to date of first documentation of progressive disease
Progression free survival (PFS) From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) Time from date of first study treatment to date of first documentation of progressive disease or death
Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires Cycles 1 and 2 (28 days per Cycle), and 30 days after last isatuximab administration (up to approximately 14 months after first study treatment administration) Comparison of patient expectations and satisfaction will be assessed using Patient Expectations and Satisfaction Questionnaires before and after subcutaneous (SC) administration, where a score of 1 = not satisfied and a score of 5 = extremely satisfied
Overall survival (OS) From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) Time from the date of first study treatment to date of death from any cause
Biomarker: Change in CD38 receptor occupancy At screening and at Day 1 of Cycle 2 (28 days per Cycle) (predose); to be stopped once the isatuximab SC dose has been selected. Change in CD38 receptor occupancy from baseline
Trial Locations
- Locations (14)
Investigational Site Number : 0360004
🇦🇺Fitzroy, Victoria, Australia
~Banner MD Anderson Cancer Center Site Number : 8400005
🇺🇸Gilbert, Arizona, United States
Investigational Site Number : 3920002
🇯🇵Okayama-shi, Okayama, Japan
Investigational Site Number : 0360003
🇦🇺Richmond, Victoria, Australia
Investigational Site Number : 0560001
🇧🇪Leuven, Belgium
City of Hope Site Number : 8400002
🇺🇸Duarte, California, United States
Gabrail Cancer Center Site Number : 8400001
🇺🇸Canton, Ohio, United States
Investigational Site Number : 0360001
🇦🇺Wollongong, New South Wales, Australia
Investigational Site Number : 0360002
🇦🇺Blacktown, New South Wales, Australia
Investigational Site Number : 2500002
🇫🇷TOULOUSE Cedex 9, France
Investigational Site Number : 2500001
🇫🇷Nantes, France
Investigational Site Number : 3920001
🇯🇵Shibuya-ku, Tokyo, Japan
Investigational Site Number : 7240002
🇪🇸Santander, Cantabria, Spain
Investigational Site Number : 7240001
🇪🇸Badalona, Catalunya [Cataluña], Spain