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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with a single dose of obe-cel
Hospital Universitari Vall Hebrón
Barcelona, Spain
RECRUITINGHospital Universitari i Politecnic La Fe
Valencia, Spain
RECRUITINGAddenbrookes Hospital
Cambridge, United Kingdom
Dose-limiting toxicities
Percentage of patients receiving obe-cel who experience dose-limiting toxicities (DLTs)
Time frame: Up to 28 days from obe-cel infusion
Adverse events
Adverse event (AE) type, frequency, severity, and relationship with obe-cel and lymphodepletion of AEs
Time frame: Up to Month 12
Remission rate according to Definition of Remission in SLE (DORIS)
Remission rate as specified by Definition of Remission in SLE (DORIS)
Time frame: Up to Month 12
Response over time according to Definition of Remission in SLE (DORIS)
Response over time as specified by Definition of Remission in SLE (DORIS)
Time frame: Up to Month 12
Time to response according to Definition of Remission in SLE (DORIS)
Time to response as specified by Definition of Remission in SLE (DORIS)
Time frame: Up to Month 12
Change over time in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
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.
Time frame: Up to Month 12
Change over time in Physician's global assessment (PGA)
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
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University College London Hospitals NHS Foundation Trust
London, United Kingdom
RECRUITINGGreat Ormond Street Hospital
London, United Kingdom
RECRUITINGManchester Royal Infirmary, Manchester University NHS Foundation Trust,
Manchester, United Kingdom
RECRUITINGTime frame: Up to Month 12
Pharmacokinetics (maximum serum concentration [Cmax]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood
Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion
Time frame: Up to Month 12
Pharmacokinetics (time to reaching maximum serum concentration [Tmax]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood
Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion
Time frame: Up to Month 12
Pharmacokinetics (area under the curve [AUC]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood
Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion
Time frame: Up to Month 12
Pharmacokinetics (last observed quantifiable concentration [Clast]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood
Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion
Time frame: Up to Month 12
Pharmacokinetics (time to reach last observed quantifiable concentration [Tlast]): Detection of CAR-T cells by polymerase chain reaction (PCR) in peripheral blood
Detection of CAR T cells measured by PCR in the peripheral blood after obe-cel infusion
Time frame: Up to Month 12
Pharmacodynamics: B cell aplasia
Depletion of circulating B cells in the peripheral blood
Time frame: Up to Month 12