Systemic Lupus Erythematosus
Conditions
Keywords
AUTO1, Obecabtagene autoleucel (obe-cel), CD19-positive chimeric antigen receptor T cell, CAR-T
Brief summary
This is a Phase 1 study of obecabtagene autoleucel (obe-cel), autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19, to establish the tolerability, safety, preliminary efficacy, and pharmacokinetics of obe-cel in patients with severe, refractory SLE.
Detailed description
This is a single-arm, open-label Phase 1 Study to determine the safety, tolerability, and preliminary efficacy of obe-cel in patients with severe, refractory SLE. Up to a maximum of 18 patients will be treated in a maximum of 3 dose levels. By using the Bayesian Optimal Interval (BOIN) design for overdose control, the Sponsor will review the Safety Review Committee (SRC) and Independent Data Monitoring Committee (IDMC) recommendation and determine if a dose level is suitable for a subsequent study.
Interventions
BIOLOGICALObecabtagene autoleucel (obe-cel)
Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with a single dose of obe-cel
Sponsors
Autolus Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
-Key Inclusion Criteria- * Women or men ≥ 18 years at screening \[Spain only\] or patients 12 to 65 years of age (inclusive) at the time of signing the informed consent \[UK only\] * Diagnosis of SLE fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus * Positive for at least one of the following autoantibodies: antinuclear antibodies (ANA) at a titer of ≥ 1:80, or anti-dsDNA (≥ 30 IU/mL) or anti-Smith (\> upper limit of normal \[ULN\]), anti-histone or anti-chromatin (\> ULN) * Severe, refractory SLE
Exclusion criteria
-Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicities | Up to 28 days from obe-cel infusion | Percentage of patients receiving obe-cel who experience dose-limiting toxicities (DLTs) |
| Adverse events | Up to Month 12 | Adverse event (AE) type, frequency, severity, and relationship with obe-cel and lymphodepletion of AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission rate according to Definition of Remission in SLE (DORIS) | Up to Month 12 | Remission rate as specified by Definition of Remission in SLE (DORIS) |
| Response over time according to Definition of Remission in SLE (DORIS) | Up to Month 12 | Response over time as specified by Definition of Remission in SLE (DORIS) |
| Time to response according to Definition of Remission in SLE (DORIS) | Up to Month 12 | Time to response as specified by Definition of Remission in SLE (DORIS) |
| Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) | Up to Month 12 | Change compared to baseline in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score. The total score is the sum of all marked SLE-related descriptors. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity. |
| Change over time in Physician's global assessment (PGA) | Up to Month 12 | Change compared to baseline in physician's global assessment (PGA) of average SLE disease severity on a visual analog scale (VAS) between 0 and 3 where 0 represents no disease, 1 represents mild disease activity, 2 represents moderate disease activity, and 3 represents a severe disease activity (highest and most severe possible disease activity). At least 10% change improvement or worsening in PGA to be clinically significant compared to baseline |
| Pharmacokinetics (maximum serum concentration [Cmax]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood | Up to Month 12 | Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion |
| Pharmacokinetics (time to reaching maximum serum concentration [Tmax]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood | Up to Month 12 | Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion |
| Pharmacokinetics (area under the curve [AUC]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood | Up to Month 12 | Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion |
| Pharmacokinetics (last observed quantifiable concentration [Clast]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood | Up to Month 12 | Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion |
| Pharmacokinetics (time to reach last observed quantifiable concentration [Tlast]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood | Up to Month 12 | Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion |
| Pharmacodynamics: B cell aplasia | Up to Month 12 | Depletion of circulating B cells in the peripheral blood |
Countries
Spain, United Kingdom
Outcome results
None listed