| May 31, 2022
|
| June 6, 2022
|
| March 6, 2024
|
| June 23, 2022
|
| May 23, 2024 (Final data collection date for primary outcome measure)
|
- Overall response rate (ORR) [ Time Frame: Up to approximately 2 years ]
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 IMWG criteria assessed by Independent Review Committee (IRC).
- Observed concentration before dosing (Cthrough) at steady state [ Time Frame: Predose at Cycle 6 Day 1 (duration of each cycle is 28 days) ]
Observed Isatuximab plasma concentration
|
| Same as current
|
|
|
- Very Good Partial Response or better rate (VGPR) [ Time Frame: Up to approximately 2 years ]
Very Good Partial Response or better rate defined as the proportion of participants with stringent complete response (sCR), complete response (CR) and very good partial response (VGPR) according to the 2016 International Myeloma Working Group (IMWG) criteria assessed by Independent Review Committee (IRC).
- Observed concentration before dosing (Ctrough) [ Time Frame: At 4 weeks i.e., predose at Cycle 2 Day 1 (duration of each cycle is 28 days) ]
Observed Isatuximab plasma concentration
- Incidence rate of infusion-reactions [ Time Frame: Up to approximately 4 years ]
Proportion of participants with infusion-reactions related events
- Percentage of participants satisfied or very satisfied with the injection method used to administer study medication [ Time Frame: At Cycle 5 Day 15 ]
Participant's satisfaction with isatuximab subcutaneous (SC) and intravenous (IV) will be assessed based on the Patient Experience and Satisfaction Questionnaires (PESQ) questionnaire.
- Duration of response (DOR) [ Time Frame: Up to approximately 2 years ]
DOR, defined as the time from the date of the first confirmed response to the date of first occurrence of progressive disease (PD) as determined by IRC or death, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better). In the absence of PD or death before the analysis cut-off date, the DOR will be censored at the date of the last valid disease assessment performed prior to initiation of a further anti-myeloma treatment or the analysis cut-off date, whichever is earlier. Participants with two or more consecutive missed assessments prior to PD or death will be censored at the last valid disease assessment.
- Time to first response (TT1R) [ Time Frame: Up to approximately 2 years ]
TT1R, defined as the time from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. Same censoring rule applies as in the DOR endpoint.
- Time to best response (TTBR) [ Time Frame: Up to approximately 2 years ]
TTBR, defined as the time from randomization to the date of first occurrence of IRC determined best overall response (PR or better) that is subsequently confirmed. Same censoring rule applies as in the DOR endpoint
- Progression free survival (PFS) [ Time Frame: Up to approximately 4 years ]
PFS, defined as the time from the date of randomization to the date of first documentation of progressive disease as determined by IRC or the date of death from any cause, whichever comes first. Responses will be determined according to IMWG criteria. Progression based on paraprotein will be confirmed based on two consecutive assessments. PFS will be censored at the date of the last valid disease assessment not showing disease progression performed prior to initiation of a further anti-myeloma treatment (if any) or the analysis cut-off date, whichever comes first. Participants with two or more consecutive missed assessments prior to PD or death will be censored at the last valid disease assessment.
- Overall survival (OS) [ Time Frame: Up to approximately 4 years ]
OS, defined as the time from the date of randomization to death from any cause. Participants without death prior to the analysis cut-off date will be censored at the last date the participant was known to be alive or the cut-off date, whichever is first.
- Progression free survival 2 (PFS2) [ Time Frame: Up to approximately 4 years ]
PFS2, defined as time from the date of randomization to the date of first documentation of PD (as assessed by investigator) after initiation of further anti-myeloma treatment or death from any cause, whichever happens first. Same censoring rule applies as in the PFS endpoint.
- Number of participants with treatment-emergent adverse events (TEAEs)/serious adverse events (SAEs). [ Time Frame: Up to approximately 4 years ]
Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen (according to the Investigator opinion), or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment.
- Pharmacokinetic (PK) parameter [ Time Frame: Up to approximately 4 years ]
Maximum plasma concentration (Cmax)
- PK parameter [ Time Frame: Up to approximately 4 years ]
Area under the plasma concentration time curve over the dosing period (AUC)
- Successful injection rate [ Time Frame: Up to approximately 4 years ]
Number of successful injections with (investigational) isatuximab injector device divided by total number of actual injections
- Percentage of participants with anti-drug antibodies (ADA) against isatuximab [ Time Frame: Up to approximately 4 years ]
An ADA positive patient was defined as a subject either having treatment-induced ADA response (no positive ADA response at baseline and any positive response in the post baseline period, including the follow-up visit) or a treatment-boosted ADA response (a positive ADA response at baseline and a ≥4-fold increase in titer in the post baseline period including the follow-up visit).
- Participant expectation questionnaire-baseline (PEQ-BL) score [ Time Frame: Cycle 1 Day 1 ((duration of each cycle is 28 days) ]
PEQ-BL is designed to assess the expectations of the participants regarding both the treatment (side effects, worth taking) and the administration method (confidence, comfortability, pain, side effects, potential time-savings), as well as to understand previous treatment experience from the participant (experience with injection methods for oncology medication).
- Patient experience and satisfaction questionnaire- follow up (PESQ-FU) score [ Time Frame: Up to approximately 4 years ]
PESQ-FU, a 9-item questionnaire is designed to follow up on participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction).
- Patient experience and satisfaction questionnaire-end of treatment (PESQ-EOT) score [ Time Frame: Up to approximately 4 years ]
PESQ-EOT, a 17-item questionnaire is designed to assess participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction). This questionnaire includes also additional items to assess participant preference on injection method (subcutaneous or intravenous) and location of administration (at home or at clinic).
- Patient's Assessment of Treatment (PAT) questionnaire score [ Time Frame: Up to approximately 4 years ]
The PAT provides patient insights on the benefits and disadvantages of treatment, including an overall Benefit/Disadvantage ratio using a final question that provides a quantitative assessment of the patient's perceived B/D. The 4-item PAT is an internally developed non-disease specific and self-administered assessment. This questionnaire contains 4 items and take approximately 2-3 minutes to complete.
- Change from baseline in the Health Resource Utilization and Productivity Questionnaire (HRUPQ) scores [ Time Frame: Baseline; up to approximately 4 years ]
Medical resource utilization and participant productivity will be collected from participants through the HRUPQ questionnaire. The questions include number, nature (emergency or routine) and duration of hospitalizations; emergency room visits and outpatient medical encounters; and employment history. The HRUPQ contains 46 items.
- Change from baseline in European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) score [ Time Frame: Baseline; up to approximately 4 years ]
EORTC QLQ-C30 is a cancer-specific questionnaire that contains 30 items and provides a multidimensional assessment of Health Related Quality of Life (HRQL).
- Change from baseline in European Organization for Research and Treatment of Cancer quality of life myeloma module (EORTC QLQ-MY20) [ Time Frame: Baseline; up to approximately 4 years ]
EORTC QLQ-MY20, a 20-item questionnaire is used to assess symptoms and side effects due to the treatment or the disease which impact HRQL in participants with multiple myeloma.
- Change from baseline in the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) scores [ Time Frame: Baseline; up to approximately 4 years ]
EQ-5D-5L questionnaire is a measure of health status that provides a simple, generic measure of health utility, and consists of 2 sections: descriptive and visual analogue scale (VAS). The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The VAS records the respondent's self-rated health on a 20 cm vertical, VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine.'
- Number of participants with chromosomal abnormalities [ Time Frame: Up to approximately 4 years ]
Explore chromosomal abnormalities (mainly but not limited to t(4;14), t(14;16), del(17p), and 1q21+)
|
- Very Good Partial Response or better rate (VGPR) [ Time Frame: Up to approximately 2 years ]
Very Good Partial Response or better rate defined as the proportion of participants with stringent complete response (sCR), complete response (CR) and very good partial response (VGPR) according to the 2016 International Myeloma Working Group (IMWG) criteria assessed by Independent Review Committee (IRC).
- Observed concentration before dosing (Ctrough) [ Time Frame: At 4 weeks i.e., predose at Cycle 2 Day 1 (duration of each cycle is 28 days) ]
Observed Isatuximab plasma concentration
- Incidence rate of infusion-reactions [ Time Frame: Up to approximately 4 years ]
Proportion of participants with infusion-reactions related events
- Percentage of participants satisfied or very satisfied with the injection method used to administer study medication [ Time Frame: At Cycle 5 Day 15 ]
Participant's satisfaction with isatuximab subcutaneous (SC) and intravenous (IV) will be assessed based on the Patient Experience and Satisfaction Questionnaires (PESQ) questionnaire.
- Duration of response (DOR) [ Time Frame: Up to approximately 2 years ]
DOR, defined as the time from the date of the first confirmed response to the date of first occurrence of progressive disease (PD) as determined by IRC or death, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better). In the absence of PD or death before the analysis cut-off date, the DOR will be censored at the date of the last valid disease assessment performed prior to initiation of a further anti-myeloma treatment or the analysis cut-off date, whichever is earlier. Participants with two or more consecutive missed assessments prior to PD or death will be censored at the last valid disease assessment.
- Time to first response (TT1R) [ Time Frame: Up to approximately 2 years ]
TT1R, defined as the time from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. Same censoring rule applies as in the DOR endpoint.
- Time to best response (TTBR) [ Time Frame: Up to approximately 2 years ]
TTBR, defined as the time from randomization to the date of first occurrence of IRC determined best overall response (PR or better) that is subsequently confirmed. Same censoring rule applies as in the DOR endpoint
- Progression free survival (PFS) [ Time Frame: Up to approximately 4 years ]
PFS, defined as the time from the date of randomization to the date of first documentation of progressive disease as determined by IRC or the date of death from any cause, whichever comes first. Responses will be determined according to IMWG criteria. Progression based on paraprotein will be confirmed based on two consecutive assessments. PFS will be censored at the date of the last valid disease assessment not showing disease progression performed prior to initiation of a further anti-myeloma treatment (if any) or the analysis cut-off date, whichever comes first. Participants with two or more consecutive missed assessments prior to PD or death will be censored at the last valid disease assessment.
- Overall survival (OS) [ Time Frame: Up to approximately 4 years ]
OS, defined as the time from the date of randomization to death from any cause. Participants without death prior to the analysis cut-off date will be censored at the last date the participant was known to be alive or the cut-off date, whichever is first.
- Progression free survival 2 (PFS2) [ Time Frame: Up to approximately 4 years ]
PFS2, defined as time from the date of randomization to the date of first documentation of PD (as assessed by investigator) after initiation of further anti-myeloma treatment or death from any cause, whichever happens first. Same censoring rule applies as in the PFS endpoint.
- Number of participants with treatment-emergent adverse events (TEAEs)/serious adverse events (SAEs). [ Time Frame: Up to approximately 4 years ]
Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen (according to the Investigator opinion), or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment.
- Pharmacokinetic (PK) parameter [ Time Frame: Up to approximately 4 years ]
Maximum plasma concentration (Cmax)
- PK parameter [ Time Frame: Up to approximately 4 years ]
Area under the plasma concentration time curve over the dosing period (AUC)
- Successful injection rate [ Time Frame: Up to approximately 4 years ]
Number of successful injections with (investigational) isatuximab injector device divided by total number of actual injections
- Percentage of participants with anti-drug antibodies (ADA) against isatuximab [ Time Frame: Up to approximately 4 years ]
An ADA positive patient was defined as a subject either having treatment-induced ADA response (no positive ADA response at baseline and any positive response in the post baseline period, including the follow-up visit) or a treatment-boosted ADA response (a positive ADA response at baseline and a ≥4-fold increase in titer in the post baseline period including the follow-up visit).
- Participant expectation questionnaire-baseline (PEQ-BL) score [ Time Frame: Cycle 1 Day 1 ((duration of each cycle is 28 days) ]
PEQ-BL is designed to assess the expectations of the participants regarding both the treatment (side effects, worth taking) and the administration method (confidence, comfortability, pain, side effects, potential time-savings), as well as to understand previous treatment experience from the participant (experience with injection methods for oncology medication).
- Patient experience and satisfaction questionnaire- follow up (PESQ-FU) score [ Time Frame: Up to approximately 4 years ]
PESQ-FU, a 9-item questionnaire is designed to follow up on participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction).
- Patient experience and satisfaction questionnaire-end of treatment (PESQ-EOT) score [ Time Frame: Up to approximately 4 years ]
PESQ-EOT, a 17-item questionnaire is designed to assess participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction). This questionnaire includes also additional items to assess participant preference on injection method (subcutaneous or intravenous) and location of administration (at home or at clinic).
- Change from baseline in the Health Resource Utilization and Productivity Questionnaire (HRUPQ) scores [ Time Frame: Baseline; up to approximately 4 years ]
Medical resource utilization and participant productivity will be collected from participants through the HRUPQ questionnaire. The questions include number, nature (emergency or routine) and duration of hospitalizations; emergency room visits and outpatient medical encounters; and employment history. The HRUPQ contains 46 items.
- Change from baseline in European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) score [ Time Frame: Baseline; up to approximately 4 years ]
EORTC QLQ-C30 is a cancer-specific questionnaire that contains 30 items and provides a multidimensional assessment of Health Related Quality of Life (HRQL).
- Change from baseline in European Organization for Research and Treatment of Cancer quality of life myeloma module (EORTC QLQ-MY20) [ Time Frame: Baseline; up to approximately 4 years ]
EORTC QLQ-MY20, a 20-item questionnaire is used to assess symptoms and side effects due to the treatment or the disease which impact HRQL in participants with multiple myeloma.
- Change from baseline in the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) scores [ Time Frame: Baseline; up to approximately 4 years ]
EQ-5D-5L questionnaire is a measure of health status that provides a simple, generic measure of health utility, and consists of 2 sections: descriptive and visual analogue scale (VAS). The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The VAS records the respondent's self-rated health on a 20 cm vertical, VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine.'
- Number of participants with chromosomal abnormalities [ Time Frame: Up to approximately 4 years ]
Explore chromosomal abnormalities (mainly but not limited to t(4;14), t(14;16), del(17p), and 1q21+)
|
| Not Provided
|
| Not Provided
|
| |
| SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM
|
| A Randomized, Phase 3, Open Label Study Evaluating Subcutaneous Versus Intravenous Administration of Isatuximab in Combination With Pomalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma (RRMM)
|
This is a randomized, multicenter, Phase 3, open-label study evaluating subcutaneous (SC) vs intravenous (IV) administration of isatuximab in combination with pomalidomide and dexamethasone (Pd) in RRMM patients (study participants) who have received at least 1 prior line of therapy including lenalidomide and a proteasome inhibitor (PI). Eligible participants will be randomized 1:1 into 1 of 2 study arms:
Arm SC: Isatuximab SC + Pd
Arm IV: Isatuximab IV + Pd
Participants will be allowed to continue therapy until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.
|
| Two study arms will be treated in 4-week cycles until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.
|
| Interventional
|
| Phase 3
|
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|
| Plasma Cell Myeloma Recurrent
|
- Drug: Isatuximab IV
Pharmaceutical form: Concentrate solution for IV infusion; Route of administration: Intravenous
- Drug: Isatuximab SC
Pharmaceutical form: Solution for subcutaneous administration; Route of administration: Subcutaneous (SC)
Other Name: SAR650984
- Drug: Dexamethasone
Pharmaceutical form: Tablet; Route of administration: Oral
- Drug: Pomalyst or equivalent
Pharmaceutical form: hard capsules; Route of administration: Oral
Other Name: Pomalyst
|
- Experimental: Isatuximab Subcutaneous (SC)
Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days).
Interventions:
- Drug: Isatuximab SC
- Drug: Dexamethasone
- Drug: Pomalyst or equivalent
- Active Comparator: Isatuximab Intravenous (IV)
Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days).
Interventions:
- Drug: Isatuximab IV
- Drug: Dexamethasone
- Drug: Pomalyst or equivalent
|
| Not Provided
|
| |
| Recruiting
|
| 534
|
| Same as current
|
| February 15, 2027
|
| May 23, 2024 (Final data collection date for primary outcome measure)
|
Inclusion Criteria:
- Participants with multiple myeloma who have received at least one prior line of anti-myeloma therapy, which must include lenalidomide and a proteasome inhibitor given alone or in combination.
- Measurable serum M-protein (≥ 0.5 g/dL) and/or urine M-protein (≥ 200 mg/24 hours) and/or serum free light chain (FLC) assay (Involved FLC assay ≥10 mg/dL and abnormal serum FLC ratio (<0.26 or >1.65)).
Exclusion Criteria:
- Primary refractory multiple myeloma participants
- Participants with prior anti-CD38 treatment: (a) administered less than 9 months before randomization or, (b) intolerant to the anti-CD38 previously received
- Prior therapy with pomalidomide
- Participants with inadequate biological tests.
- Significant cardiac dysfunction
- Participants diagnosed or treated for another malignancy within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, and in situ malignancy, or low risk prostate cancer after curative therapy
- Concomitant plasma cell leukemia
- Active primary amyloid light -chain amyloidosis
- Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment
- Know active Hepatitis A infection. Current active or chronic hepatitis B (HBV) or hepatitis C (HCV) infection. Participants with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed.
- Women of childbearing potential or male participant with women of childbearing potential who do not agree to use highly effective method of birth control
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
|
| Sexes Eligible for Study: |
All |
|
| 18 Years and older (Adult, Older Adult)
|
| No
|
| Contact: Trial Transparency email recommended (Toll free for US & Canada) |
800-633-1610 ext Option 6 |
Contact-US@sanofi.com |
|
|
| Argentina, Australia, Brazil, Canada, Chile, China, Czechia, France, Germany, Greece, Hungary, Italy, Japan, Norway, Poland, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
|
|
|
| |
| NCT05405166
|
EFC15951
U1111-1261-5846 ( Registry Identifier: ICTRP )
2023-508869-32 ( Registry Identifier: CTIS )
2021-002485-41 ( EudraCT Number )
|
| Yes
|
| Studies a U.S. FDA-regulated Drug Product: |
Yes |
| Studies a U.S. FDA-regulated Device Product: |
No |
|
| Plan to Share IPD: |
Yes |
| Plan Description: |
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org. |
|
| Sanofi
|
| Same as current
|
| Sanofi
|
| Same as current
|
| Not Provided
|
| Study Director: |
Clinical Sciences & Operations |
Sanofi |
|
| Sanofi
|
| March 2024
|
