Description:
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
Title
- Brief Title: Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
- Official Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
TCD15484
- SECONDARY ID:
2018-001996-19
- SECONDARY ID:
U1111-1211-9525
- NCT ID:
NCT04045795
Conditions
Interventions
Drug | Synonyms | Arms |
---|
isatuximab SAR650984 | Sarclisa | Dose regimen 4 |
pomalidomide | | Dose regimen 1 |
dexamethasone | | Dose regimen 1 |
isatuximab SAR650984 | Sarclisa | Dose regimen 1 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose regimen 1 | Experimental | Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle | - pomalidomide
- dexamethasone
- isatuximab SAR650984
|
Dose regimen 2 | Experimental | Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle | - pomalidomide
- dexamethasone
- isatuximab SAR650984
|
Dose regimen 3 | Experimental | Isatuximab SC administration dose level 3 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle | - pomalidomide
- dexamethasone
- isatuximab SAR650984
|
Dose regimen 4 | Experimental | Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle | - isatuximab SAR650984
- pomalidomide
- dexamethasone
|
Dose regimen 5 | Experimental | Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle | - isatuximab SAR650984
- pomalidomide
- dexamethasone
|
Eligibility Criteria
Inclusion criteria:
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in the
protocol.
- Participant must be above 18 years of age or country's legal age of majority if the
legal age is >18 years old, at the time of signing the informed consent.
- Participant has been previously diagnosed with multiple myeloma (MM) based on standard
criteria and currently requires treatment because MM has relapsed following a
response, according to International Myeloma Working Group (IMWG) criteria.
- Participant has received at least two previous therapies including lenalidomide and a
proteasome inhibitor and has demonstrated disease progression on last therapy or after
completion of the last therapy.
- Participants with measurable disease defined as at least one of the following:
- Serum M protein ≥ 0.5 g/dL (≥5 g/L).
- Urine M protein ≥ 200 mg/24 hours.
- 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).
- Male or female: Contraceptive use by men or women.
Exclusion criteria:
- Malignancy within 3 years prior to enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status score >2.
- Inadequate hematological, liver or renal function.
- Serum calcium (corrected for albumin) level above the upper limit of normal (ULN)
range.
- Patients with prior anti-CD38 treatment are excluded if:
- Refractory to anti-CD38 treatment defined as progression on or within 60 days of
the last dose of the anti-CD38 or,
- Intolerant to the anti-CD38 previously received or,
- Progression after initial response on anti-CD38 therapy with a washout period
inferior to 9 months before the first dose of isatuximab SC or IV.
- Participant did not achieve a minimal response or better to at least one of the
previous lines of treatment (ie, primary refractory disease is not eligible).
- Received any investigational drug within 14 days or 5 half-lives of the
investigational drug, whichever is longer.
- Prior anti-cancer therapy within 14 days.
- Any >Grade 1 adverse reaction unresolved from previous treatments according to the
NCI-CTCAE v5.0. The presence of alopecia or peripheral neuropathy ≤ Grade 2 without
pain is allowed.
- Previous allogeneic stem cell transplantation with active Graft Versus Host Disease or
being under immunosuppressive therapy in the last 2 months previously to the inclusion
in the trial.
- Daily requirement for corticosteroids.
- Known to be HIV+ or to have hepatitis A or uncontrolled or active hepatitis B virus
(HBV) infection (patients with positive HBsAg [HBsAg] and/or HBV DNA) or active HCV
(HCV) infection (positive HCV RNA and negative anti-HCV).
- Active tuberculosis and severe infections requiring treatment with antibiotic
parenteral administration.
- 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.
- History of erythema multiforme or severe hypersensitivity to prior immunomodulatory
drugs (IMiDs).
- Hypersensitivity or history of intolerance to immunomodulatory drugs (IMiDs),
dexamethasone, 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 histamine H2 blockers or would prohibit further treatment with these
agents.
- Inability to tolerate thromboprophylaxis.
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Assessment of adverse events (AEs) |
Time Frame: | Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration) |
Safety Issue: | |
Description: | Number of participants with adverse events |
Secondary Outcome Measures
Measure: | Estimation of absolute bioavailability of isatuximab |
Time Frame: | Day 8 |
Safety Issue: | |
Description: | Absolute bioavailability of isatuximab SC, expressed as a percentage, estimated from AUC0-168h obtained after intravenous (IV) and extravascular (EV) administration |
Measure: | Overall response rate (ORR) |
Time Frame: | From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) |
Safety Issue: | |
Description: | 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 |
Measure: | Duration of response (DOR) |
Time Frame: | From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) |
Safety Issue: | |
Description: | Time from the date of the first response to the date of first progressive disease (PD) or death, whichever happens first |
Measure: | Time to response (TTR) |
Time Frame: | From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) |
Safety Issue: | |
Description: | Time from the date of first study treatment to the first response |
Measure: | Time to progression (TTP) |
Time Frame: | From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) |
Safety Issue: | |
Description: | Time from date of first study treatment to date of first documentation of progressive disease |
Measure: | Overall survival (OS) |
Time Frame: | From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) |
Safety Issue: | |
Description: | Time from the date of first study treatment to date of death from any cause |
Measure: | Clinical benefit rate (CBR) |
Time Frame: | From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) |
Safety Issue: | |
Description: | Proportion of patients with sCR, CR, VGPR, PR or minimal response (MR) according to IMWG criteria |
Measure: | Progression free survival (PFS) |
Time Frame: | From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration) |
Safety Issue: | |
Description: | Time from date of first study treatment to date of first documentation of progressive disease or death |
Measure: | Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires |
Time Frame: | 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) |
Safety Issue: | |
Description: | 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 |
Measure: | Immunogenicity: Anti drug antibody levels |
Time Frame: | Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle) |
Safety Issue: | |
Description: | Incidence of patients with anti drug antibodies against isatuximab |
Measure: | Biomarker: Change in CD38 receptor occupancy |
Time Frame: | 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. |
Safety Issue: | |
Description: | Change in CD38 receptor occupancy from baseline |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sanofi |
Trial Keywords
- Anti-CD38 monoclonal antibody
Last Updated
June 3, 2021