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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06508489




Registration number
NCT06508489
Ethics application status
Date submitted
27/06/2024
Date registered
18/07/2024

Titles & IDs
Public title
A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies
Scientific title
A Phase 1/Phase 2, Randomized, Open-label, Multi Cohort, Multi Center, Study Assessing the Safety, Tolerability and Preliminary Efficacy of SAR443579 a Natural Killer Cell Engager (NKCE) Targeting CD123, Administered With Different Agents in Participants With CD123 Expressing Hematological Malignancies
Secondary ID [1] 0 0
U1111-1280-6173
Secondary ID [2] 0 0
TCD17796
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - SAR443579
Treatment: Drugs - venetoclax
Treatment: Drugs - azacitidine

Experimental: Substudy 01: SAR443579 + azacitidine + venetoclax - Part 1: Safety run-in: SAR443579 treatment will begin with an identified starting dose. Safety run-in will proceed according to the incidence of DLTs.


Treatment: Other: SAR443579
Pharmaceutical form: Powder for solution for infusion Route of administration: intravenous infusion

Treatment: Drugs: venetoclax
Pharmaceutical form :Film coated tablet Route of administration: oral

Treatment: Drugs: azacitidine
Pharmaceutical form: Lyophilized powder for suspension for injection Route of administration: intravenous or subcutaneous
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events (AEs)/serious adverse events (SAEs)/adverse events of special interest (AESIs), laboratory abnormalities
Timepoint [1] 0 0
Day 1 to 30 days after the last administration of study treatment
Primary outcome [2] 0 0
Substudy 01: Incidence of dose limiting toxicities (DLTs) (escalation part)
Timepoint [2] 0 0
Day 1 to Day 28
Primary outcome [3] 0 0
Substudy 01: Complete Remission (CR) rate (optimization part)
Timepoint [3] 0 0
Day 1 to 30 days after the last administration of study treatment
Primary outcome [4] 0 0
Substudy 01: Complete Remission (CR) rate (expansion part)
Timepoint [4] 0 0
Day 1 up to 6 months
Secondary outcome [1] 0 0
Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and clinically significant laboratory abnormalities (expansion part)
Timepoint [1] 0 0
Day 1 to 30 days after the last administration of study treatment
Secondary outcome [2] 0 0
Incidence of anti-drug anti body (ADA) against SAR443579
Timepoint [2] 0 0
Day 1 to 30 days after the last administration of study treatment
Secondary outcome [3] 0 0
Substudy 01: Percentage of participants with Minimal residual disease (expansion part)
Timepoint [3] 0 0
Day 1 up to 6 months
Secondary outcome [4] 0 0
Substudy 01: Pharmacokinetic (PK) parameter of SAR443579: Ctrough
Timepoint [4] 0 0
Day 1 up to 10 cycles (each cycle 28 days)
Secondary outcome [5] 0 0
Substudy 01: PK parameter of venetoclax: Cmax
Timepoint [5] 0 0
Day 1 to Day 28
Secondary outcome [6] 0 0
Substudy 01: PK parameter of azacitidine: Cmax
Timepoint [6] 0 0
Day 1 to Day 28
Secondary outcome [7] 0 0
Substudy 01: PK parameter of venetoclax: AUC
Timepoint [7] 0 0
Day 1 to Day 28
Secondary outcome [8] 0 0
Substudy 01: PK parameter of azacitidine: AUC
Timepoint [8] 0 0
Day 1 to Day 28
Secondary outcome [9] 0 0
Substudy 01: Composite Complete Remission (CRc) rate
Timepoint [9] 0 0
Day 1 up to 6 months
Secondary outcome [10] 0 0
Substudy 01: Overall response rate (expansion part)
Timepoint [10] 0 0
Day 1 up to 6 months
Secondary outcome [11] 0 0
Substudy 01: Duration of CR (expansion part)
Timepoint [11] 0 0
Day 1 up to 24 months after the last administration from study treatment
Secondary outcome [12] 0 0
Substudy 01: Duration of CRc (expansion part)
Timepoint [12] 0 0
Day 1 up to 24 months after the last administration from study treatment
Secondary outcome [13] 0 0
Substudy 01: Duration of overall response (expansion part)
Timepoint [13] 0 0
Day 1 up to 24 months after the last administration from study treatment
Secondary outcome [14] 0 0
Substudy 01: Alternative CR rate (expansion part)
Timepoint [14] 0 0
Day 1 up to 6 months
Secondary outcome [15] 0 0
Substudy 01: Duration of alternative CR (expansion part)
Timepoint [15] 0 0
Day 1 up to 24 months after the last administration from study treatment
Secondary outcome [16] 0 0
Substudy 01: Event-free survival (EFS) (expansion part)
Timepoint [16] 0 0
Day 1 up to 24 months after the last administration from study treatment
Secondary outcome [17] 0 0
Substudy 01: Overall survival (expansion part)
Timepoint [17] 0 0
Day 1 up to 24 months after the last administration from study treatment
Secondary outcome [18] 0 0
Substudy 01: Rate of hematopoietic stem cell transplantation (HSCT) procedures immediately following study treatment administration but prior to subsequent therapy for treatment of AML (all parts)
Timepoint [18] 0 0
Day 1 up to 24 months after the last administration from study treatment
Secondary outcome [19] 0 0
Substudy 01: Time to treatment failure (TTF) (expansion part)
Timepoint [19] 0 0
Day 1 up to 24 months after the last administration from study treatment
Secondary outcome [20] 0 0
Substudy 01: Rate of conversion from transfusion dependence to transfusion independence (all parts)
Timepoint [20] 0 0
Day 1 to Day 56
Secondary outcome [21] 0 0
Substudy 01: Rate of participants who are transfusion independent at baseline and remain independent during 56-day post-baseline period (all parts)
Timepoint [21] 0 0
Day 1 to Day 56

Eligibility
Key inclusion criteria
- Participants with CD123-expressing hematological neoplasm per the 5th edition of the WHO Classification of Hematolymphoid Tumors.

Substudy 01:

* Participants must be =18 years of age
* Confirmed diagnosis of Acute Myeloid Leukemia
* Ineligible for intensive chemotherapy. Ineligible for intensive chemotherapy is defined by the following criteria:

A) = 75 years of age, OR

B) 18 to 74 years of age and meeting one or more of the following:

1. Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
2. Cardiac history of congestive heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) =50% or symptomatic coronary heart disease confirmed by coronarography or cardiac imaging.
3. Diffusing capacity of the lungs for carbon monoxide (DLCO) =65% or forced expiratory volume (FEV1) =65%.
4. Creatinine clearance =30 to <45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
5. Moderate hepatic impairment with total bilirubin >1.5 to =3.0x upper limit of normal (ULN).

* Subject with an Eastern Cooperative Oncology Group (ECOG) performance status as follows:

a) 0 to 2 for participants =75 years of age or b) 0 to 3 for participants 18 to 74 years of age.

* For participants =75 years of age, adequate renal function demonstrated by a creatinine clearance =30 mL/min, calculated by modification of diet in renal disease (MDRD)
* Subject with adequate liver function demonstrated by the following:

1. For participants 18 to 74 years of age, aspartate aminotransferase (AST) =3.0 × ULN, alanine aminotransferase (ALT) =3.0 × ULN and bilirubin =3.0 × ULN, unless considered due to leukemic organ involvement ?5 × ULN.
2. For participants =75 years of age, aspartate aminotransferase (AST) =3.0 × ULN, alanine aminotransferase (ALT) =3.0 × ULN and bilirubin =1.5 × ULN, unless considered due to leukemic organ involvement ?5 × ULN.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that is not controlled)
* Known second malignancy either progressing or requiring active treatment within the last 3 years prior to first IMP administration
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or SARS-CoV-2 infection. With exception for:

1. HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tests positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tests negative for HBsAg and HBV DNA, is eligible.
2. A participant who tests positive for anti-HCV antibodies and has undetectable HCV RNA without receiving antiviral treatment for HCV is eligible.
* Active, known, or suspected clinically significant autoimmune disease that has required systemic treatment in the past 2 years prior to first IMP administration, except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
* Predicted life expectancy =3 months.
* Medical conditions requiring treatment with medications with narrow therapeutic index that are substrates of CYP enzymes and that cannot be closely monitored to allow for dose adjustment.
* Ongoing adverse event of NCI CTCAE [Version 5.0] Grade 2 or greater severity cause by any prior anti-cancer therapy

Substudy 01:

* Patient with Acute Promyelocytic Leukemia (APL)
* Known active central nervous system involvement with AML at the time of enrollment as evidenced by cytology or pathology
* Cardiovascular disease of New York Heart Association (NYHA) Class =2.
* Malabsorption syndrome or other condition that precludes enteral route of administration
* A baseline QTc interval of (using the Fridericia correction calculation) >470 msec.
* Subject has received treatment with at least one of the following:

1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for AML other than hydroxyurea used for disease control prior to the initiation of study therapy.
2. Experimental therapies for AML.
3. Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
12/02/2029
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Investigational Site Number : 0360002 - Wollongong
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Melbourne
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-US@sanofi.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


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/NCT06508489