| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed/refractory multiple myeloma (RRMM) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 25.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10086466 |
| E.1.2 | Term | Relapsed/refractory multiple myeloma |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| • The primary objective is to describe the efficacy of isatuximab SC in combination with carfilzomib and dexamethasone (Kd) |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate patient preference for the On Body Delivery System (OBDS) versus manual administration of isatuximab SC
• To assess the safety of isatuximab SC in combination with Kd
• To assess the local tolerability of isatuximab SC in combination with Kd
• To characterize the pharmacokinetics (PK) of isatuximab in combination with Kd after manual and OBDS administration
• To evaluate the efficacy of isatuximab SC in combination with Kd
• To assess the potential immunogenicity of isatuximab SC
• To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 3 months following study treatment discontinuation, even if has undergone a successful vasectomy.
Capable of giving signed informed consent. |
|
| E.4 | Principal 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 are excluded if: a) Progression on or within 60 days after end of anti-CD38 mAb treatment or failure to achieve at least MR to treatment (ie, refractory to anti-CD38) with a washout period inferior to 9 months before the first isatuximab administration 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 the potential participation in a clinical trial. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall response rate (ORR). 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). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 6 months after the Last Participant In (LPI) i.e., approximately 16 months |
|
| E.5.2 | Secondary end point(s) |
1. Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6. Patient preference for method of administration defined as the proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6 using the patient experience and satisfaction questionnaire version 2 (PESQ v2).
2. Incidence rate of infusion reactions (IRs).
3. Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters.
4. Incidence rate of injection site reactions (ISRs).
5. PK concentration: trough plasma concentration (Ctrough). Blood samples will be collected for measurement of isatuximab concentrations.
6. Proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria assessed by IRC.
7. Duration of response (DOR). DOR defined as time from date of first IRC-determined response for participants achieving PR or better to first documentation of progressive disease (PD) determined by IRC or death, whichever occurred first.
8. Time to first response (TT1R). TT1R defined as time from randomization to first IRC determined response (PR or better) that is subsequently confirmed.
9. Time to best response (TTBR). TTBR defined as time from randomization to first occurrence of IRC determined best response (PR or better) that is subsequently confirmed.
10. Progression free survival (PFS). PFS defined as time from the date of randomization to the date of first documentation of PD as determined by IRC or the date of death from any cause, whichever comes first.
11. Overall survival (OS). OS defined as time from the date of randomization to death from any cause.
12. Incidence of participants with anti-drug antibodies (ADA) against isatuximab.
13. Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously. PEQ-BL v2 is a participant assessed questionnaire. It will be completed at baseline prior to study treatment administration or other study related procedures. This questionnaire has been 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).
14. Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously. PESQ v2 is a participant assessed questionnaire. It has been 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). The PESQ v2 includes items to assess preference on subcutaneous injection method (manual and OBDS).
15. Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ). Medical resource utilization and participant productivity will be collected from participants through a specific questionnaire developed by Sanofi. The data collected include number, nature (emergency or routine) and duration of hospitalizations, emergency room visits and outpatient medical encounters and employment history.
16. Health Related Quality of Life (HRQL). HRQL is assessed using the European Organization for Research and Treatment of Cancer (EORTC) myeloma module with 20 items (QLQ-MY20) and EORTC quality of life questionnaire with 30 questions (QLQ-C30); a total of 50 items. The EORTC QLQ-C30 provides a comprehensive assessment of the principal HRQL dimensions identified as relevant by cancer patients. The EORTC QLQ-MY20 is to be used in conjunction with the EORTC QLQ-C30 to assess symptoms and side effects due to the treatment or the disease which impact HRQL in participants with MM.
17. European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ5D-5L). Health status is assessed using the EQ-5D-5L, a standardized measure of health status that provides a simple, generic measure of health utility, and consists of 2 sections: descriptive and 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’. This information can be used as a quantitative measure of health as judged by the individual respondents. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 6 months from LPI i.e., approximately 16 months
2, 4, 6, 7, 8, 9, 10, 11, 14, 15, 16, 17. 18 months after LPI i.e., approximately 28 months
3. 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
5. Cycle 2 Day 1 and Cycle 6 Day 1 (1 Cycle = 28 days)
12. From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e., approximately 13 months (1 Cycle = 28 days)
13. Baseline |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Brazil |
| Japan |
| Switzerland |
| Czechia |
| Greece |
| Portugal |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
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