An Open-label, Study to Assess Safety, Efficacy and Cellular Kinetics of YTB323 in Severe, Refractory Systemic Lupus Erythematosus

Novartis

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Lupus Nephritis

Systemic Lupus Erythematosus

Treatments

Drug: YTB323

Study type

Interventional

Funder types

Industry

Identifiers

NCT05798117

2022-001796-14 (EudraCT Number)

CYTB323G12101

Details and patient eligibility

About

The study is intended to assess safety, efficacy and cellular kinetics of YTB323 treatment in participants with severe refractory systemic lupus erythematosus.

Enrollment

21 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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).

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