A study to investigate subcutaneous isatuximab in combination with carfilzomib and dexamethasone in adult participants with relapsed and/or refractory multiple myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Jan 2023 → ongoing

Decision date (initial)

2024-05-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-508870-27-00

EudraCT number

2022-002767-30

WHO UTN

U1111-1280-5090

ClinicalTrials.gov

NCT05704049

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

• The primary objective is to describe the efficacy of isatuximab SC in combination with carfilzomib and dexamethasone (Kd)- Cohorts 1 to 3
• The primary objective is to characterize the PK of isatuximab in combination with Kd after
manual and OBDS administration- Cohorts 4 to 5

Secondary objectives 7

1. To evaluate patient preference for the On Body Delivery System (OBDS) versus manual administration of isatuximab SC
2. To assess the safety of isatuximab SC in combination with Kd
3. To assess the local tolerability of isatuximab SC in combination with Kd
4. To characterize the pharmacokinetics (PK) of isatuximab in combination with Kd after manual and OBDS administration
5. To evaluate the efficacy of isatuximab SC in combination with Kd
6. To assess the potential immunogenicity of isatuximab SC
7. To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status

Conditions and MedDRA coding

Cancer - Relapsed/refractory multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants must have a documented diagnosis of multiple myeloma (MM)
2. -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).
3. -Participant with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy.
4. 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.
5. Male participants agree to practice true abstinence or agree to use approved contraception methods while receiving study treatment, during dose interruptions and at least 5 months following study treatment discontinuation, even if has undergone a successful vasectomy.
6. Capable of giving signed informed consent.

Exclusion criteria 6

1. -Primary refractory MM defined as participants who have never achieved at least a minimal response (MR) with any treatment during the disease course
2. -Participants with prior anti-CD38 treatment if: a) administered <9 months before first isatuximab administration or randomization as applicable or, b) Intolerant to the anti- CD38 previously received
3. -Prior treatment with carfilzomib
4. -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
5. -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
6. -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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Overall response rate (ORR) – Cohorts 1 to 3
2. Maximum observed concentration (Cmax) over Cycle 1- Cohorts 4 to 5
3. Cumulative area under the curve over the first 4 weeks (AUC4weeks) of isatuximab treatment- Cohorts 4 to 5

Secondary endpoints 17

1. Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6
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)
6. Overall response rate (ORR)
7. Duration of response (DOR)
8. Time to first response (TT1R)
9. Time to best response (TTBR)
10. Progression free survival (PFS)
11. Overall survival (OS)
12. Incidence of participants with anti-drug antibodies (ADA) against isatuximab
13. Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously
14. Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously
15. Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ)
16. Health Related Quality of Life (HRQL)
17. European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 12

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications