A Multi-center, Open-label, Phase 1b Study to Assess the Pharmacokinetics, Safety, and Efficacy of Subcutaneous and Intravenous Isatuximab (SAR650984) in Combination With Pomalidomide and Dexamethasone, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 56
- 试验地点
- 14
- 主要终点
- PK assessment: Ctrough
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose regimen 1
Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: pomalidomide (Drug)
Dose regimen 1
Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: dexamethasone (Drug)
Dose regimen 1
Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: isatuximab SAR650984 SC (Drug)
Dose regimen 2
Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: pomalidomide (Drug)
Dose regimen 2
Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: dexamethasone (Drug)
Dose regimen 2
Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: isatuximab SAR650984 SC (Drug)
Dose regimen 3
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
干预措施: pomalidomide (Drug)
Dose regimen 3
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
干预措施: dexamethasone (Drug)
Dose regimen 3
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
干预措施: isatuximab SAR650984 SC (Drug)
Dose regimen 3
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
干预措施: Investigational injector device (Device)
Dose regimen 4
Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: isatuximab SAR650984 IV (Drug)
Dose regimen 4
Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: pomalidomide (Drug)
Dose regimen 4
Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: dexamethasone (Drug)
Dose regimen 5
Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: isatuximab SAR650984 IV (Drug)
Dose regimen 5
Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: pomalidomide (Drug)
Dose regimen 5
Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
干预措施: dexamethasone (Drug)
结局指标
主要结局
PK assessment: Ctrough
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Time of Clast (tlast)
PK assessment: AUC0 T
时间窗: 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
时间窗: Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Time to reach Cmax (tmax)
次要结局
- Overall response rate (ORR)(From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration))
- 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 to response (TTR)(From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration))
- Immunogenicity: Anti drug antibody levels(Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle))
- Estimation of absolute bioavailability of isatuximab(Day 8)
- Clinical benefit rate (CBR)(From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration))
- Time to progression (TTP)(From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration))
- Progression free survival (PFS)(From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration))
- 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))
- Overall survival (OS)(From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration))
- 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.)