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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05798117




Registration number
NCT05798117
Ethics application status
Date submitted
27/02/2023
Date registered
4/04/2023

Titles & IDs
Public title
An Open-label, Study to Assess Safety, Efficacy and Cellular Kinetics of YTB323 in Severe, Refractory Systemic Lupus Erythematosus
Scientific title
An Open-label, Multi-center, Phase 1/2 Study to Assess Safety, Efficacy and Cellular Kinetics of YTB323 in Participants With Severe, Refractory Systemic Lupus Erythematosus
Secondary ID [1] 0 0
2022-001796-14
Secondary ID [2] 0 0
CYTB323G12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Lupus Erythematosus 0 0
Lupus Nephritis 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - YTB323

Experimental: YTB323 - Single infusion of YTB323


Treatment: Drugs: YTB323
Single infusion of YTB323
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with AEs and SAEs
Timepoint [1] 0 0
Day 1 to 2 years
Secondary outcome [1] 0 0
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Maximum observed blood concentration Cmax)
Timepoint [1] 0 0
Pre-dose, up to 2 years
Secondary outcome [2] 0 0
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Area under plasma concentration -time AUC)
Timepoint [2] 0 0
Pre-dose, up to 2 years
Secondary outcome [3] 0 0
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Time to reach maximum concentration Tmax)
Timepoint [3] 0 0
Pre-dose, up to 2 years
Secondary outcome [4] 0 0
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Terminal elimination half-life T1/2)
Timepoint [4] 0 0
Pre-dose, up to 2 years
Secondary outcome [5] 0 0
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Last measurable concentration Clast)
Timepoint [5] 0 0
Pre-dose, up to 2 years
Secondary outcome [6] 0 0
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Time to reach last measurable concentration Tlast)
Timepoint [6] 0 0
Pre-dose, up to 2 years
Secondary outcome [7] 0 0
Number of patients with anti-drug antibodies
Timepoint [7] 0 0
Pre-dose, up to 2 years
Secondary outcome [8] 0 0
Level of T cell activation by YTB323
Timepoint [8] 0 0
Pre-dose, up to 2 years
Secondary outcome [9] 0 0
Number of patients infused with planned target dose
Timepoint [9] 0 0
Day 1
Secondary outcome [10] 0 0
Change from pre-dose up to 2 years in the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score
Timepoint [10] 0 0
Pre-dose, up to 2 years
Secondary outcome [11] 0 0
Change from pre-dose up to 2 years in Physician's global assessment (PGA)
Timepoint [11] 0 0
Pre-dose, up to 2 years
Secondary outcome [12] 0 0
Change from pre-dose up to 2 years in Lupus Low Disease Activity State (LLDAS)
Timepoint [12] 0 0
Pre-dose, up to 2 years
Secondary outcome [13] 0 0
Remission rate
Timepoint [13] 0 0
Up to 2 years
Secondary outcome [14] 0 0
Change from pre-dose up to 2 years in Urinary protein creatinine ratio (UPCR)
Timepoint [14] 0 0
Pre-dose, up to 2 years
Secondary outcome [15] 0 0
Incidence of Complete renal response (CRR)
Timepoint [15] 0 0
Up to 2 years

Eligibility
Key inclusion criteria
* Signed informed consent
* Adequate renal, hepatic, cardiac, hematological and pulmonary function
* Men and women with SLE, aged =18 years and =65 years at screening, fulfilling the 2019 European League Against Rheumatism EULAR/ACR classification criteria for SLE.
* Patient must be positive for at least one of the following autoantibodies at screening: antinuclear antibodies (ANA) at a titer of =1:80, or anti dsDNA (above the ULN); or anti-Sm (above the ULN)
* Active (severe) disease as defined by SLEDAI-2K = 8 (not including the SLEDAI-2K domains of lupus headache, cerebrovascular accident, organic brain syndrome) and at least one of the following significant SLE related organ involvements:
* Renal
* At least moderate or severe peri/myocarditis
* At least moderate or severe pleuritis or other lung involvement
* Vasculitis
* Failure to respond to two or more standard immunosuppressive therapies (including one of mycophenolate or cyclophosphamide), unless contraindicated or having experienced documented adverse events or intolerance related to such immunosuppressive drugs not allowing their further use, in combination with glucocorticoids and failure to respond to at least one biological agent (unless contraindicated, the patient deemed ineligible by the Investigator or not available in a country).
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Clinically significant active, opportunistic, chronic or recurrent infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, such as COVID-19 etc.) one month prior to or during screening. Patients who have had at least one severe infection that required prolonged hospitalization in the intensive care setting within 5 years prior to screening and/or at least one severe infection that required prolonged hospitalization within one year prior to screening.
* Uncontrolled diabetes mellitus, lung diseases or any other illness that are not related to SLE that in the opinion of the Investigator would jeopardize the ability of the patient to tolerate lymphodepletion and CD19 CAR-T cell therapy
* Prior history of malignancy except for localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis
* Any patients requiring medications prohibited by the protocol
* Any psychiatric condition or disability making compliance with treatment or informed consent impossible
* Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy)
* History of bone marrow/hematopoietic stem cell or solid organ transplantation
* Female participants who are pregnant or breastfeeding, or intending to conceive during the course of the study
* Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using a highly effective method of contraception starting from the time of enrollment to at least 12 months after the YTB323 infusion (or longer if required as per local regulations) and until CAR-T cells are no longer present by qPCR on two consecutive tests
* Sexually active males unwilling to use a condom during intercourse from the time enrollment for at least 12 months after the YTB323 infusion and until CAR-T cells are no longer present by qPCR on two consecutive tests
* Any acute, severe lupus related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible; thus, makes the patient ineligible for CD19 CAR-T therapy as judged by the Investigator, such as acute central nervous system (CNS) lupus (e.g. psychosis, epilepsy) or catastrophic antiphospholipid syndrome
* Significant, likely irreversible organ damage related to SLE, e.g. end stage renal disease, that in the opinion of the Investigator renders CD19 CAR-T cell therapy would be unlikely to benefit the patient
* B cell aplasia

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
28/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
9/10/2026
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
France
State/province [3] 0 0
Lille
Country [4] 0 0
France
State/province [4] 0 0
Paris 13
Country [5] 0 0
France
State/province [5] 0 0
Pessac Cedex
Country [6] 0 0
France
State/province [6] 0 0
Strasbourg Cedex
Country [7] 0 0
Germany
State/province [7] 0 0
Freiburg
Country [8] 0 0
Germany
State/province [8] 0 0
Mainz
Country [9] 0 0
Spain
State/province [9] 0 0
Catalunya
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
Switzerland
State/province [11] 0 0
Bern
Country [12] 0 0
Switzerland
State/province [12] 0 0
Lausanne

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceutical
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.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?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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/NCT05798117