Evaluation of Pharmacokinetics, Safety, and Preliminary Efficacy of Isatuximab in Chinese Patients With Relapsed and/or Refractory Multiple Myeloma

An Open-label, Multi-center Study to Evaluate the Pharmacokinetics, Safety, and Preliminary Efficacy of Isatuximab in Chinese Patients With Relapsed and/or Refractory Multiple Myeloma

Primary Objective:

To evaluate the pharmacokinetics (PK) of isatuximab.

Secondary Objectives:

• To evaluate the safety and tolerability of isatuximab.
• To assess the preliminary antitumor effect of isatuximab.
• To evaluate the immunogenicity of isatuximab.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Isatuximab SAR650984

Detailed Description

The duration of the study for an individual patient will include a screening period of up to 21 days, a treatment period of repeated 28-day cycles, and a follow-up period. End of treatment visit will be done at 30 (±7) days after last treatment.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Investigational Site Number 1560003
  • Nanjing, China, 210029
    • Investigational Site Number 1560002
  • Tianjin, China, 300020
    • Investigational Site Number 1560001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Known diagnosis of symptomatic multiple myeloma.
• At least 2 prior lines of therapies which must include treatment with at least 1 of an immunomodulatory drug (IMiD) or a proteasome inhibitor (PI). The patients must have received an IMiD or a PI for ≥2 cycles or ≥2 months of treatment.
• Patients must have been responsive to at least 1 prior line of therapy (minimal response or better).
• Refractory to the most recently received IMiD or PI included therapy (ie, patients must have progressed during or within 60 days of completion of treatment with IMiD or PI). For patients who have received more than 1 type of IMiD or PI, their disease must be refractory to the most recent one.

• Measurable disease defined as at least 1 of the following:

  • Serum M-protein ≥0.5 g/dL (≥5 g/L);
  • Urine M-protein ≥200 mg/24 hours.
• Written informed consent.

Exclusion criteria:

• <18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status >2.
• Life expectancy of less than 3 months.
• Pretreated with any anticluster of differentiation (CD) 38 agent.
• Concurrent plasma cell leukemia.
• Known amyloidosis.
• Disease measurable only by serum free light chain (FLC) analysis.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isatuximab; Administered intravenously every week in Cycle 1 (4 weeks) followed by every 2 weeks (Q2W) in subsequent cycles.	Drug: Isatuximab SAR650984; Pharmaceutical form: Concentrate for solution Route of administration: Intravenous; Other Names: Sarclisa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PK: Cmax	To evaluate the maximum observed concentration (Cmax)	Cycle 1, up to 168 hours after start of infusion
Assessment of PK: tmax	To evaluate the time to reach Cmax (tmax)	Cycle 1, up to 168 hours after start of infusion
Assessment of PK: AUC0-168h	To evaluate area under the plasma concentration versus time curve over the dosing interval (AUC0-168h)	Cycle 1, up to 168 hours after start of infusion
Assessment of PK: Ceoi	To evaluate the concentration observed at the end of an IV infusion (Ceoi)	Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1; Cycle duration is 28 days
Assessment of PK: Ctrough	To evaluate concentration observed just before investigational medicinal product (IMP) administration during repeated dosing (Ctrough)	Up to approximately 40 weeks (Cycle 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Treatment Emergent Adverse Events (TEAEs)/Serious Adverse Events (SAE) based on standard and systematic assessment including infusion associated reactions (IARs), laboratory test abnormalities, vital signs and ECOG performance status	Up to 30 days after the last IMP administration
Anti-tumor activity: Overall response (ORR)	Proportion of patients achieving: stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to International Myeloma Working Group (IMWG 2016) criteria	Up to 12 months after last patient treated
Anti-Tumor Activity: Duration of response (DOR)	Time from the date of the first determined response to the date of subsequent determined progressive disease or death, whichever happens earlier	Up to 12 months after last patient treated
Anti-Tumor Activity: Time to progression (TTP)	Time interval from the date of first IMP administration to the date of the first assessed disease progression using IMWG criteria	Up to 12 months after last patient treated
Anti-Tumor Activity: Progression free survival (PFS)	Time interval from the date of first IMP administration to the date of the first documentation of disease progression or death due to any cause, whichever comes first	Up to 12 months after last patient treated
Anti-Tumor Activity: Overall survival (OS)	Time interval from the date of first IMP administration to death due to any cause	Up to 12 months after last patient treated
Immunogenicity	To evaluate the presence of antidrug antibodies (ADA) to isatuximab	Up to 13 months (10 cycles + 3 months) after last patient treated

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2018
• Primary Completion (Actual): September 6, 2020
• Study Completion (Actual): August 25, 2023

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (Actual): November 7, 2018

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Anti-CD38 monoclonal antibody
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: TED15085; U1111-1195-6028 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No