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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04045795




Registration number
NCT04045795
Ethics application status
Date submitted
2/08/2019
Date registered
6/08/2019

Titles & IDs
Public title
Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
Scientific 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)
Secondary ID [1] 0 0
U1111-1211-9525
Secondary ID [2] 0 0
TCD15484
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - isatuximab SAR650984 IV
Treatment: Drugs - pomalidomide
Treatment: Drugs - dexamethasone
Treatment: Drugs - isatuximab SAR650984 SC
Treatment: Devices - Investigational injector device

Experimental: Dose regimen 1 - Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Experimental: Dose regimen 2 - Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Experimental: Dose regimen 3 - Isatuximab SC administration dose level 3 using the investigational injector device once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Experimental: Dose regimen 4 - Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Experimental: Dose regimen 5 - Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle


Treatment: Drugs: isatuximab SAR650984 IV
Pharmaceutical form: solution

Route of administration: intravenous

Treatment: Drugs: pomalidomide
Pharmaceutical form: tablet

Route of administration: oral

Treatment: Drugs: dexamethasone
Pharmaceutical form: tablet

Route of administration: oral

Treatment: Drugs: isatuximab SAR650984 SC
Pharmaceutical form: solution

Route of administration: subcutaneous

Treatment: Devices: Investigational injector device
Subcutaneous administration
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Assessment of adverse events (AEs)
Assessment method [1] 0 0
Number of participants with adverse events
Timepoint [1] 0 0
Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration)
Primary outcome [2] 0 0
Pharmacokinetic (PK) assessment: Ceoi
Assessment method [2] 0 0
Concentration observed at the end of infusion (Ceoi)
Timepoint [2] 0 0
Baseline to end of treatment (EOT) after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary outcome [3] 0 0
PK assessment: Cmax
Assessment method [3] 0 0
Maximum concentration observed after the first infusion (Cmax)
Timepoint [3] 0 0
Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary outcome [4] 0 0
PK assessment: tmax
Assessment method [4] 0 0
Time to reach Cmax (tmax)
Timepoint [4] 0 0
Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary outcome [5] 0 0
PK assessment: Clast
Assessment method [5] 0 0
Last concentration observed above the lower limit of quantification after the first infusion (Clast)
Timepoint [5] 0 0
Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary outcome [6] 0 0
PK assessment: tlast
Assessment method [6] 0 0
Time of Clast (tlast)
Timepoint [6] 0 0
Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary outcome [7] 0 0
PK assessment: Ctrough
Assessment method [7] 0 0
Concentration observed just before treatment administration during repeated dosing (Ctrough)
Timepoint [7] 0 0
Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary outcome [8] 0 0
PK assessment: AUClast
Assessment method [8] 0 0
Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast) (AUClast)
Timepoint [8] 0 0
Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Primary outcome [9] 0 0
PK assessment: AUC0 T
Assessment method [9] 0 0
Area under the plasma concentration versus time curve calculated over the dosing interval T (168h or 336h) (AUC0 T)
Timepoint [9] 0 0
Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Secondary outcome [1] 0 0
Estimation of absolute bioavailability of isatuximab
Assessment method [1] 0 0
Absolute bioavailability of isatuximab SC, expressed as a percentage, estimated from AUC0-168h obtained after intravenous (IV) and extravascular (EV) administration
Timepoint [1] 0 0
Day 8
Secondary outcome [2] 0 0
Overall response rate (ORR)
Assessment method [2] 0 0
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
Timepoint [2] 0 0
From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary outcome [3] 0 0
Duration of response (DOR)
Assessment method [3] 0 0
Time from the date of the first response to the date of first progressive disease (PD) or death, whichever happens first
Timepoint [3] 0 0
From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary outcome [4] 0 0
Time to response (TTR)
Assessment method [4] 0 0
Time from the date of first study treatment to the first response
Timepoint [4] 0 0
From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary outcome [5] 0 0
Time to progression (TTP)
Assessment method [5] 0 0
Time from date of first study treatment to date of first documentation of progressive disease
Timepoint [5] 0 0
From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary outcome [6] 0 0
Overall survival (OS)
Assessment method [6] 0 0
Time from the date of first study treatment to date of death from any cause
Timepoint [6] 0 0
From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary outcome [7] 0 0
Clinical benefit rate (CBR)
Assessment method [7] 0 0
Proportion of patients with sCR, CR, VGPR, PR or minimal response (MR) according to IMWG criteria
Timepoint [7] 0 0
From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary outcome [8] 0 0
Progression free survival (PFS)
Assessment method [8] 0 0
Time from date of first study treatment to date of first documentation of progressive disease or death
Timepoint [8] 0 0
From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Secondary outcome [9] 0 0
Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires
Assessment method [9] 0 0
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
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Immunogenicity: Anti drug antibody levels
Assessment method [10] 0 0
Incidence of patients with anti drug antibodies against isatuximab
Timepoint [10] 0 0
Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Secondary outcome [11] 0 0
Biomarker: Change in CD38 receptor occupancy
Assessment method [11] 0 0
Change in CD38 receptor occupancy from baseline
Timepoint [11] 0 0
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.

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/03/2024
Sample size
Target
Accrual to date
Final
56
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Investigational Site Number : 0360002 - Blacktown
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Wollongong
Recruitment hospital [3] 0 0
Investigational Site Number : 0360004 - Fitzroy
Recruitment hospital [4] 0 0
Investigational Site Number : 0360003 - Richmond
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
Belgium
State/province [4] 0 0
Leuven
Country [5] 0 0
France
State/province [5] 0 0
Nantes
Country [6] 0 0
France
State/province [6] 0 0
TOULOUSE Cedex 9
Country [7] 0 0
Japan
State/province [7] 0 0
Okayama
Country [8] 0 0
Japan
State/province [8] 0 0
Tokyo
Country [9] 0 0
Spain
State/province [9] 0 0
Cantabria
Country [10] 0 0
Spain
State/province [10] 0 0
Catalunya [Cataluña]

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04045795