Obe-cel in Severe, Refractory Systemic Lupus Erythematosus With Active Lupus Nephritis

Not Applicable

Not yet recruiting

• Conditions: Lupus Nephritis
• Interventions: Biological: Obecabtagene autoleucel

• Registration Number: NCT07053800
• Lead Sponsor: Autolus Limited

Brief Summary

This trial aims to find out if obe-cel gets rid of harmful B cells that contribute to systemic lupus erythematosus (SLE)/lupus nephritis (LN) when available treatments have not worked (refractory).

The objective is to look for benefits of obe-cel in making signs of LN completely disappear (remission) at 6 months after treatment in patients with severe, active LN. We will also look for other benefits of obe-cel for up to 24 months after treatment, including the percentage of patients who respond to obe-cel treatment, SLE/LN activity, time to and length of remission, and quality of life. We will also assess how long obe-cel stays in the body and the safety of obe-cel.

Main trial endpoint is to look at the percentage of patients whose LN has completely disappeared 6 months after obe-cel treatment, as shown by urine and blood samples that test kidney function and use of other medicines to treat SLE/LN after obe-cel infusion.

Secondary trial endpoints are to measure in different ways SLE/LN disease activity and rate of treatment response over 24 months after obe-cel treatment. We will also measure the number, frequency and severity of side effects. The doctor will take small samples of blood and urine to look for biological signs of SLE/LN during the trial. We will monitor the amount of obe-cel in the body and check for B cells coming back.

The trial includes only 1 group of patients (single arm). Patients and doctors will know the treatment (obe-cel) each patient receives during the trial (open-label). This trial is the second phase in testing obe-cel in SLE (Phase II). We will screen patients to make sure they are suitable for the trial, and then collect white blood cells (leukapheresis) to make obe-cel. Patients will have lymphodepletion chemotherapy to help make obe-cel treatment more effective. They will then receive a single infusion of obe-cel. We will check patients closely in the first 28 days after obe-cel treatment. Then we will do assessments every month for 12 months and every 3 months for up to at least 24 months.

Around 30 teenage and adult patients aged 12 to 65 years, weighing at least 40 kg, with severe refractory SLE, severe active LN, and an inadequate response to hydroxychloroquine in combination with corticosteroids, calcineurin inhibitors, and other therapies that target B cells. Patients must not have recent lupus affecting the brain or more than 1 severe lupus related flare, organ damage so severe obe-cel treatment is unlikely to work, recent illnesses affecting the nervous system, heart disease that's not under control, any active infections, recently taken other immunosuppressive therapies, malignant cancer within the past 2 years, history of organ or stem cell transplants, or be pregnant or planning to become pregnant during the trial.

Pre-conditioning chemotherapy (lymphodepletion): eligible patients will receive fludarabine and cyclophosphamide for up to 3 days in preparation for receiving the obe-cel infusion.

Obe-cel infusion: eligible patients will receive obe-cel once, 3 to 10 days after lymphodepletion.

Diagnostic and monitoring procedures: at enrollment, SLE diagnosis is based on the 2019 European League Against Rheumatism and American College of Rheumatology criteria. Severe active SLE is defined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K). Severe active LN is defined as SLE related kidney involvement based on taking a sample (biopsy) of kidney tissue and assessing kidney function from 24 hour urine collections. We will assess safety via reporting of side effects. We will assess benefit via complete or partial renal remission, Definition of Remission in SLE, Lupus Low Disease Activity State criteria, SLEDAI 2K, Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI Flare Index, and other measures of treatment impact.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-05-13
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-26
• Last Update Submitted: 2025-06-26
• Study Start: 2025-07-01
• Study First Posted: 2025-07-08
• Last Update Posted: 2025-07-08
• Primary Completion: 2028-12
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• Willing and able to give written informed consent for participation in the study or written informed consent signed by a legal guardian or representative

• Ability and willingness to adhere to protocol's SoA and other requirements

• Participants must be 12 to 65 years of age inclusive at the time of signing the informed consent. For participants aged < 18 years, both legally authorized representative consent and participant assent is required.

• A body weight ≥ 40 kg.

• Female Participants: - a female participant is eligible to participate if she is not pregnant or breastfeeding

• 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 1 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]), antihistone or anti-chromatin (> ULN).

• Severe, Active SLE defined as:

  • Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥ 8 points (of which 4 are non-laboratory items and with the exclusion of points associated with neurological findings [SLEDAI-2K items 1-7]) AND
  • Severe active LN

• Refractory SLE, defined as lack of response, insufficient response, or lack of sustained response to all the following treatments with or without combination with other medications as per current treatment guidelines (ACR 2024; Fanouriakis et al, 2024; KDIGO 2024):

  1. Hydroxychloroquine in combination with corticosteroids AND
  2. Calcineurin inhibitors (e.g., cyclosporine, voclosporin, tacrolimus) AND
  3. B cell-targeting agents (e.g., belimumab, anti CD20 mAb) Exposure to both calcineurin inhibitors and B cell-targeting agents is required unless such treatments are not recommended based on local approved prescribing information, considered intolerable, or not approved or available in the country at the time of enrolment.

NOTE: Treatments/combinations should be used for at least 6 months (with dosage based on local approved prescribing information or institutional treatment guidelines), unless there is intolerance or clinical reasons that in the opinion of the Investigator are related to such drugs and would prevent their further use.

Exclusion Criteria

• Any medications prohibited by the protocol

• Prior treatment at any time with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g., CAR T cell therapy).

• History of anaphylactic or severe systemic reaction to fludarabine, cyclophosphamide or any of their metabolites.

• Any other investigational treatments must have had a wash out of at least 5 half-lives.

• Recurrent neuropsychiatric lupus at any point prior to screening, or active, severe, or unstable neuropsychiatric lupus within 1 year from screening.

• More than 1 acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible; thus, making the participant ineligible for CD19 CAR T therapy (1 treatment of flare is allowed and participant must be fully rescreened; such cases should be discussed with the Medical Monitor).

• 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 unlikely to benefit the participant.

• Diagnosis of clinically significant uveitis.

• History or presence of:

  a. Within 3 months before screening visit: i. clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, or stroke ii. evidence of deep venous thrombosis or pulmonary embolism

• History or presence of severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.

• History of primary antiphospholipid antibody syndrome.

• Clinically significant, uncontrolled heart disease not due to SLE (New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled cardiac arrhythmia, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless the participant has a pacemaker) or a recent (within 12 months of screening) cardiac event.

• Active or uncontrolled fungal, bacterial, or viral infection

• History of malignant neoplasms unless disease free for at least 24 months (basal cell or squamous cell carcinoma in situ, or in situ breast cancer on hormonal therapy allowed).

• History of heart, lung, renal, liver transplant or hematopoietic stem cell transplant.

• Planning pregnancy, pregnant, or lactating.

• Participants are not eligible if there is evidence of B cell aplasia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Obe-cel	Obecabtagene autoleucel	-

Primary Outcome Measures

Name	Time	Method
To evaluate the efficacy of obe-cel as measured by the proportion of participants who achieve complete renal response (CRR) at 6 months post-obe-cel infusion without rescue medications, among all participants who received obe-cel infusion	Month 6	Proportion of participants with CRR.; CRR is defined as: * Urine protein creatinine ratio (UPCR) ≤ 0.5 mg/mg AND; * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 or no confirmed decrease from baseline eGFR of \> 20% AND; * Did not receive rescue medication

Secondary Outcome Measures

Name	Time	Method
To evaluate the efficacy of obe-cel as measured by the proportion of participants who achieve response according to Definition of Remission in SLE (DORIS) at 6 months post-obe-cel infusion, among all patients who received obe-cel infusion	Month 6	Disease remission according to DORIS at 6 months. Remission defined as clinical SLE disease activity index-2000 (SLEDAI-2K) = 0, Evaluator's Global Assessment \< 0.5 (0-3), prednisolone 5 mg/day or less, and stable antimalarials (van Vollenhoven et al, 2021)
Proportion of participants with CRR.	Up to Month 24	CRR is defined as: * Urine protein creatinine ratio (UPCR) ≤ 0.5 mg/mg AND; * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 or no confirmed decrease from baseline eGFR of \> 20% AND; * Did not receive rescue medication
Time to CRR.	Up to Month 24	CRR is defined as: * Urine protein creatinine ratio (UPCR) ≤ 0.5 mg/mg AND; * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 or no confirmed decrease from baseline eGFR of \> 20% AND; * Did not receive rescue medication
Duration of CRR.	Up to Month 24	CRR is defined as: * Urine protein creatinine ratio (UPCR) ≤ 0.5 mg/mg AND; * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 or no confirmed decrease from baseline eGFR of \> 20% AND; * Did not receive rescue medication
Proportion of participants with Partial Renal Response (PRR)	Up to Month 24	PRR is defined as ≥ 50% reduction in UPCR from baseline.
Remission over time, as specified by DORIS. Disease response according to time to renal event.	Up to Month 24	Renal event is defined as a pre-specified \> 30% decrease in eGFR from baseline.
Time to response, as specified by DORIS. Disease response according to time to renal event.	Up to Month 24	Renal event is defined as a pre-specified \> 30% decrease in eGFR from baseline.
Change in disease activity according to Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) - score over time.	Up to Month 24	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.
Proportion of participants achieving SLEDAI-2K score of 0.	Up to Month 24	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.
Disease response according to Lupus Low Disease Activity State (LLDAS) - remission over time, as specified by the definition of remission in LLDAS.	Up to Month 24	Definition of remission: * SLEDAI-2K ≤ 4; * No new features of lupus disease activity compared to the previous assessment; * Physician's Global Assessment (PGA) ≤ 1 on a visual analog scale from 0-3; * Current prednisolone (or equivalent) dose ≤ 7.5 mg daily
Disease response according to Lupus Low Disease Activity State (LLDAS) - time to remission, as specified by the definition of remission in LLDAS.	Up to Month 24	Definition of remission: * SLEDAI-2K ≤ 4; * No new features of lupus disease activity compared to the previous assessment; * PGA ≤ 1 on a visual analog scale from 0-3; * Current prednisolone (or equivalent) dose ≤ 7.5 mg daily
Disease response according to Lupus Low Disease Activity State (LLDAS) - duration of remission as specified by the definition of remission in LLDAS.	Up to Month 24	Definition of remission: * SLEDAI-2K ≤ 4; * No new features of lupus disease activity compared to the previous assessment; * PGA ≤ 1 on a visual analog scale from 0-3; * Current prednisolone (or equivalent) dose ≤ 7.5 mg daily
Time to new SLE activity according to Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI-2K Flare Index (SFI) - time from obe-cel infusion to first disease flare according to definition of flare in SFI, as scored by SLEDAI-2K.	Up to Month 24	Flare Intensity Definitions: * Mild/moderate: 1) increase of SLEDAI by ≥ 3 points; and/or 2) new/worse skin, stomatitis, serositis, arthritis, fever; and/or 3) increase in PGA by ≥ 1.0; and/or 4) treatment intensification: increase in prednisone \< 0.5 mg/kg or added nonsteroidal anti-inflammatory drugs (NSAIDs) or hydroxychloroquine.; * Severe: 1) increase of SLEDAI by \> 12; and/or 2) new/worse CNS involvement, vasculitis, glomerulonephritis, myositis, platelet counts \< 60,000/mm\^3, hemolytic anemia (hemoglobin \< 70 g/L), requiring doubling of prednisone dose or dose \> 0.5 mg/kg; and/or 3) need for hospitalization due to SLE; and/or 4) any manifestation requiring prednisone \> 0.5 mg/kg or new immunosuppressive therapy; and/or 4) increase in PGA to \> 2.5.
Change from baseline in PGA.	Up to Month 24	PGA is used to provide the physician's overall assessment 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).
Change from baseline in Patient's Global Assessment (PtGA).	Up to Month 24	The Participant Global Assessment is part of the HAQ-DI instrument and is given as a single question, scored from 0-100 with higher numbers representing worse perceived disease activity or overall health.
Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score.	Up to Month 24	Score range 0-52. A score of less than 30 indicates severe fatigue. The higher the score, the better the quality of life.
Change from baseline in Disability Health Assessment Questionnaire - Disability Index (HAQ-DI).	Up to Month 24	HAQ-DI instrument consists of 2 visual analog scales 1) the PtGA and 2) Pain scale. Both are scored from 0-100 with higher numbers representing worse perceived disease activity or overall health.
Change from baseline in Short Form Health Survey (SF-36).	Up to Month 24	The SF-36 score range is from 0 to 100. Higher scores indicate better perceived health, while lower scores indicate greater disability or poorer health. The SF-36 assesses eight health domains: physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health.
Change from baseline in EuroQoL (EQ)-5D.	Up to Month 24	EQ-5D index scores range from -0.59 to 1, where 1 is the best possible health state; EQ visual analog scale scores range from 0 to 100, where 100 is the best possible health state.
Frequency of hospitalization to manage obe-cel-related toxicity.	Up to Month 24	Frequency of hospitalization to manage obe-cel-related toxicity
Duration of hospitalization to manage obe-cel-related toxicity.	Up to Month 24	Duration of hospitalization to manage obe-cel-related toxicity
Frequency of critical care support to manage obe-cel-related toxicity	Up to Month 24	Frequency of critical care support to manage obe-cel-related toxicity
To evaluate HCRU after treatment with obe-cel - Duration of critical care support to manage obe-cel-related toxicity	Up to Month 24	Duration of critical care support to manage obe-cel-related toxicity
Frequency of cytokine release syndrome (CRS)	Up to Month 24	Frequency of cytokine release syndrome (CRS)
Severity of CRS	Up to Month 24	Severity of CRS will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Duration of CRS	Up to Month 24	Duration of CRS
Frequency of immune effector cell-associated neurotoxicity syndrome (ICANS)	Up to Month 24	Frequency of immune effector cell-associated neurotoxicity syndrome (ICANS)
Severity of ICANS	Up to Month 24	Severity of ICANS will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Duration of ICANS	Up to Month 24	Duration of ICANS
Frequency of other identified risks - Myelosuppression and Immunosuppression	Up to Month 24	The number and percentage of patients experiencing Myelosuppression and Immunosuppression
Frequency of other identified risks - Prolonged Cytopenia	Up to Month 24	The number and percentage of patients experiencing Prolonged Cytopenia
Frequency of other identified risks - Hypogammaglobulinemia	Up to Month 24	The number and percentage of patients experiencing Hypogammaglobulinemia
Frequency of other identified risks - Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS)	Up to Month 24	The number and percentage of patients experiencing Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS)
Frequency of other identified risks - Hypersensitivity Reactions	Up to Month 24	The number and percentage of patients experiencing Hypersensitivity Reactions
Frequency of other identified risks - Secondary Malignancies	Up to Month 24	The number and percentage of patients experiencing Secondary Malignancies
Frequency of other identified risks - Systemic lupus erythematosus (SLE) Flare	Up to Month 24	The number and percentage of patients experiencing Systemic lupus erythematosus (SLE) Flare
Frequency of other identified risks - Renal Biopsy	Up to Month 24	The number and percentage of patients experiencing complications of Renal Biopsy
Frequency of other identified risks - Leukapheresis	Up to Month 24	The number and percentage of patients experiencing complications of Leukapheresis
Severity of other identified risks - Myelosuppression and Immunosuppression	Up to Month 24	Severity of Myelosuppression and Immunosuppression will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Severity of other identified risks - Prolonged Cytopenia	Up to Month 24	Severity of Prolonged Cytopenia will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Severity of other identified risks - Hypogammaglobulinemia	Up to Month 24	Severity of Hypogammaglobulinemia will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Severity of other identified risks - Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS)	Up to Month 24	Severity of Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS) will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Severity of other identified risks - Hypersensitivity Reactions	Up to Month 24	Severity of Hypersensitivity Reactions will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Severity of other identified risks - Secondary Malignancies	Up to Month 24	Severity of Secondary Malignancies will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Severity of other identified risks - Systemic lupus erythematosus (SLE) Flare	Up to Month 24	Severity of Systemic lupus erythematosus (SLE) Flare will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Severity of other identified risks - Renal Biopsy	Up to Month 24	Severity of complications of Renal Biopsy will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Severity of other identified risks - Leukapheresis	Up to Month 24	Severity of complications of Leukapheresis will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening consequences; Grade 5 = Fatal.
Duration of other identified risks - Myelosuppression and Immunosuppression	Up to Month 24	Duration of other Myelosuppression and Immunosuppression
Duration of other identified risks - Prolonged Cytopenia	Up to Month 24	Duration of Prolonged Cytopenia
Duration of other identified risks - Hypogammaglobulinemia	Up to Month 24	Duration of Hypogammaglobulinemia
Duration of other identified risks - Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS)	Up to Month 24	Duration of Hemophagocytic Lymphohistiocytosis (HLH) / Macrophage Activation Syndrome (MAS)
Duration of other identified risks - Hypersensitivity Reactions	Up to Month 24	Duration of Hypersensitivity Reactions
Duration of other identified risks - Secondary Malignancies	Up to Month 24	Duration of Secondary Malignancies
Duration of other identified risks - Systemic lupus erythematosus (SLE) Flare	Up to Month 24	Duration of Systemic lupus erythematosus (SLE) Flare
Duration of other identified risks - Renal Biopsy	Up to Month 24	Duration of complications of Renal Biopsy
Duration of other identified risks - Leukapheresis	Up to Month 24	Duration of complications of Leukapheresis
To evaluate safety of obe-cel	Up to Month 24	Number of participants with Adverse event (AE), with abnormal laboratory tests results and abnormal vital signs
To evaluate the pharmacokinetics (PK) of obe-cel - maximum concentration (Cmax)	Pre-infusion at Day -6 and at 9 timepoints post-infusion between Days 1 and 28, followed by Month 2, Month 3, then 3-monthly to Month 24	Analysis of cells in peripheral blood by polymerase chain reaction and/or flow cytometry at a range of time points in the peripheral blood.
To evaluate the pharmacokinetics (PK) of obe-cel - time to maximum concentration (Tmax)	Pre-infusion at Day -6 and at 9 timepoints post-infusion between Days 1 and 28, followed by Month 2, Month 3, then 3-monthly to Month 24	Analysis of cells in peripheral blood by polymerase chain reaction and/or flow cytometry at a range of time points in the peripheral blood.
To evaluate the pharmacokinetics (PK) of obe-cel - area under the curve from Day 0 to Day 28 (AUC0-28d)	Pre-infusion at Day -6 and at 9 timepoints post-infusion between Days 1 and 28, followed by Month 2, Month 3, then 3-monthly to Month 24	Analysis of cells in peripheral blood by polymerase chain reaction and/or flow cytometry at a range of time points in the peripheral blood.
To evaluate the pharmacokinetics (PK) of obe-cel - area under the curve from Day 0 to Day 84 (AUC0-84d)	Pre-infusion at Day -6 and at 9 timepoints post-infusion between Days 1 and 28, followed by Month 2, Month 3, then 3-monthly to Month 24	Analysis of cells in peripheral blood by polymerase chain reaction and/or flow cytometry at a range of time points in the peripheral blood.
To evaluate the pharmacokinetics (PK) of obe-cel - last observed quantifiable concentration (Clast)	Pre-infusion at Day -6 and at 9 timepoints post-infusion between Days 1 and 28, followed by Month 2, Month 3, then 3-monthly to Month 24	Analysis of cells in peripheral blood by polymerase chain reaction and/or flow cytometry at a range of time points in the peripheral blood.
To evaluate the pharmacokinetics (PK) of obe-cel - time to last observed quantifiable concentration (Tlast)	Pre-infusion at Day -6 and at 9 timepoints post-infusion between Days 1 and 28, followed by Month 2, Month 3, then 3-monthly to Month 24	Analysis of cells in peripheral blood by polymerase chain reaction and/or flow cytometry at a range of time points in the peripheral blood.
To evaluate pharmacodynamics (PD) of obe-cel	Pre-infusion at screening and Day -6 and post-infusion at Day 1, Day 28, Month 2, Month 3, then 3-monthly to Month 12 and 6 monthly to Month 24	Detection of B cells in the peripheral blood over time
To evaluate indicators of autoimmunity - Autoantibody	Pre-infusion at Day -6 and post infusion at Day 28, Month 3, then 3-monthly to Month 12 and 6 monthly to Month 24	Change from baseline in serum autoantibody concentration (antinuclear antibody \[ANA\], anti-double stranded DNA \[anti-dsDNA\], anti-Smith, anti-RNA binding protein \[anti-RBP\])
To evaluate indicators of autoimmunity - Antiphospholipid profile - beta-2 glycoprotein	Pre-infusion at Day -6 and post infusion at Day 28, Month 3, then 3-monthly to Month 12 and 6 monthly to Month 24	Change from baseline in beta-2 glycoprotein
To evaluate indicators of autoimmunity - Antiphospholipid profile - lupus anticoagulant	Pre-infusion at Day -6 and post infusion at Day 28, Month 3, then 3-monthly to Month 12 and 6 monthly to Month 24	Change from baseline in lupus anticoagulant
To evaluate indicators of autoimmunity - Antiphospholipid profile - anticardiolipin antibodies	Pre-infusion at Day -6 and post infusion at Day 28, Month 3, then 3-monthly to Month 12 and 6 monthly to Month 24	Change from baseline in anticardiolipin antibodies
o evaluate indicators of autoimmunity - Complement	Pre-infusion at Day -6 and post infusion at Day 28, Month 3, then 3 monthly to Month 12 and 6 monthly to Month 24	Change from baseline in complement
o evaluate indicators of autoimmunity - total (CH50)	Pre-infusion at Day -6 and post infusion at Day 28, Month 3, then 3 monthly to Month 12 and 6 monthly to Month 24	Change from baseline in total (CH50)
o evaluate indicators of autoimmunity - Complements C3 and C4	Pre-infusion at Day -6 and post infusion at Day 28, Month 3, then 3 monthly to Month 12 and 6 monthly to Month 24	Change from baseline in C3 and C4