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

NCT05798117 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CYTB323G121012022-001796-14
• Study Type: interventional
• Target: 21
• Locations: 5 countries
• Sites: 10

Brief Summary

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

Conditions

Systemic Lupus Erythematosus; Lupus Nephritis

Keywords

CAR-T, YTB323, Lupus, SLE, LN, severe refractory SLE

Outcome Measures

Primary Outcomes (1)

• Number of participants with AEs and SAEs

  Long term safety follow up

  Day 1 to 2 years

Secondary Outcomes (15)

• CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Maximum observed blood concentration Cmax)

  Pre-dose, up to 2 years

• CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Area under plasma concentration -time AUC)

  Pre-dose, up to 2 years

• CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Time to reach maximum concentration Tmax)

  Pre-dose, up to 2 years

• CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Terminal elimination half-life T1/2)

  Pre-dose, up to 2 years

• CAR transgene levels by quantitative polymerase chain reaction (qPCR) in blood (Last measurable concentration Clast)

  Pre-dose, up to 2 years

Study Arms (1)

YTB323

EXPERIMENTAL

Single infusion of YTB323

Drug: YTB323

Interventions

YTB323 DRUG

Single infusion of YTB323

YTB323

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Clayton, Victoria, 3168, Australia

Location

Novartis Investigative Site

Paris, 75013, France

Location

Novartis Investigative Site

Pessac, 33604, France

Location

Novartis Investigative Site

Strasbourg, 67091, France

Location

Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Bern, 3010, Switzerland

Location

Novartis Investigative Site

Lausanne, 1011, Switzerland

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: April 4, 2023
• Study Start: February 28, 2023
• Primary Completion (Estimated): September 9, 2026
• Study Completion (Estimated): September 9, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DE (2); AU (1); ES (2); CH (2); FR (3)