AUTOLOGOUS ENRICHED T CELLS RETROVIRALLY TRANSDUCED TO EXPRESS TWO CHIMERIC ANTIGEN RECEPTORS TARGETING CD19 AND CD22 for Systemic lupus erythematosus with active lupus nephritis

Inclusion criteria

• {"criterion_text":"- Diagnosis of SLE fulfilling the 2019 European League Against Rheumatism(EULAR)/American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus.\n- Positive for at least 1 of the following autoantibodies: antinuclear antibodies (ANA) at a titer of ≥ 1:80, or anti-dsDNA or anti-Smith.\n- Severe, Active SLE\n- Severe active LN\n- Refractory SLE"}

Exclusion criteria

• {"criterion_text":"- Within 1 month prior to leukapheresis to 7 days before leukapheresis: - Use of anti-CD20 therapy. - Immunization with a live or attenuated vaccine. - New therapy classes or drugs not previously used for the individual participant’s treatment.\n- Active or uncontrolled fungal, bacterial, viral (e.g., pneumocystis or tuberculosis, or atypical mycobacteria, cytomegalovirus, herpes simplex or zoster infections, or coronavirus disease 2019), or other infection requiring systemic antimicrobials for management from 30 days prior to screening through obe-cel treatment.\n- Active or latent hepatitis B or active hepatitis C.\n- History of heart, lung, renal, liver transplant or hematopoietic stem cell transplant.\n- Human immunodeficiency virus, human T-lymphotropic virus 1 or 2, or syphilis-positive test at screening.\n- History of or current malignant neoplasms unless disease-free for at least 5 years (basal cell or squamous cell carcinoma in situ, or in situ breast cancer on hormonal therapy allowed).\n- Planning pregnancy, pregnant, or lactating.\n- Participants are not eligible if the below laboratory criteria are met during screening. NOTE: If 1 or more laboratory parameters do not satisfy eligibility, it may be repeated 1 time within the 30-day screening period after discussion with the Medical Monitor. a. Neutrophil count < 1,000/μL b. Platelet count < 50,000/μL c. Hemoglobin < 7 g/dL for SLE-related hemolytic anemia or < 8 g/dL for all other participants d. Evidence of B cell aplasia e. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 2.5 × ULN f. Total bilirubin > 1.5 × ULN for participants without Gilbert’s syndrome or direct bilirubin > 1 × ULN in participants with Gilbert’s syndrome g. International normalized ratio (INR) and activated partial thromboplastin clotting time (aPTT) > 1.5 ULN\n- Left ventricular ejection fraction < 45% (or < institute’s lower limit of normal) confirmed by echocardiogram (ECHO).\n- Oxygen saturation (SpO2)< 90% in the absence of oxygen support.\n- Prior treatment at any time with anti-CD19 therapy (including bispecifics), adoptive T cell therapy or any prior gene therapy product (e.g., CAR T cell therapy).\n- Recurrent neuropsychiatric lupus at any point prior to screening, or active, severe, or unstable neuropsychiatric lupus within 1 year from screening.\n- History of anaphylactic or severe systemic reaction to fludarabine, cyclophosphamide or any of their metabolites.\n- Any other investigational treatments must have had a wash out of at least 5 half-lives.\n- 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).\n- History or presence of: Within 3 months before screening visit: - Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, or stroke. - Evidence of deep venous thrombosis or pulmonary embolism.\n- Significant, likely irreversible organ damage related to SLE (e.g., end-stage renal disease [ESRD]) that in the opinion of the Investigator renders CD19 CAR T cell therapy unlikely to benefit the participant. Potential participants requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require these during the duration of the study are excluded from study participation.\n- Diagnosis of clinically significant uveitis.\n- History or presence of severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.\n- History or presence of antiphospholipid antibody syndrome.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Proportion of participants with CRR, defined as: • Urine Protein Creatinine Ratio (UPCR) ≤ 0.5 mg/mg AND • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 or no decrease from baseline eGFR of > 20% AND • Did not receive rescue medicine Time frame: Month 6","definition_or_measurement_approach":"CRR defined by UPCR ≤ 0.5 mg/mg AND eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline eGFR of >20% AND no receipt of rescue medicine; assessed at Month 6."}

Secondary endpoints

• {"endpoint_text":"- Remission rate as specified by DORIS Time Frame: Month 6","definition_or_measurement_approach":"Remission measured per DORIS criteria at Month 6."}
• {"endpoint_text":"- Proportion of participants with CRR. Time Frame: Up to Month 24","definition_or_measurement_approach":"Proportion achieving CRR (as defined in primary endpoint) assessed up to Month 24."}
• {"endpoint_text":"- Time to CRR. Time Frame: Up to Month 24","definition_or_measurement_approach":"Time from infusion to first documented CRR, measured up to Month 24."}
• {"endpoint_text":"- Duration of CRR. Time Frame: Up to Month 24","definition_or_measurement_approach":"Duration (persistence) of CRR following achievement, assessed up to Month 24."}
• {"endpoint_text":"- Proportion of participants with PRR, defined as: • ≥ 50% reduction in UPCR from baseline Time Frame: Up to Month 24","definition_or_measurement_approach":"PRR defined by ≥50% reduction in UPCR from baseline; assessed up to Month 24."}
• {"endpoint_text":"- Time to PRR. Time Frame: Up to Month 24","definition_or_measurement_approach":"Time from infusion to first documented PRR, measured up to Month 24."}
• {"endpoint_text":"- Duration of PRR. Time Frame: Up to Month 24","definition_or_measurement_approach":"Duration of PRR following achievement, assessed up to Month 24."}
• {"endpoint_text":"- Remission over time, time to response, as specified by DORIS Time Frame: Up to Month 24","definition_or_measurement_approach":"Remission dynamics and time to response per DORIS criteria, assessed up to Month 24."}
• {"endpoint_text":"- Time to renal event. Renal event defined as: • Confirmed decrease from baseline in eGFR (pre-specified as a > 30% decrease) Time Frame: Up to Month 24","definition_or_measurement_approach":"Time to renal event defined as confirmed >30% decrease in eGFR from baseline, assessed up to Month 24."}
• {"endpoint_text":"- SLEDAI-2K score over time and proportion of participants achieving SLEDAI-2K score of 0. Time Frame: Up to Month 24","definition_or_measurement_approach":"SLEDAI-2K scores tracked over time; proportion achieving score of 0 assessed up to Month 24."}
• {"endpoint_text":"- Remission over time, time to remission, and duration of remission as specified by the definition of remission in LLDAS. Time Frame: Up to Month 24","definition_or_measurement_approach":"Remission per LLDAS definition: time course, time to remission, and duration assessed up to Month 24."}
• {"endpoint_text":"- Time from obe-cel infusion to first disease flare as specified by the definition of flare in SFI NOTE: SLEDAI-2K will be used to score SFI. Time Frame: Up to Month 24","definition_or_measurement_approach":"Time from infusion to first disease flare per SFI; SLEDAI-2K used for scoring; assessed up to Month 24."}
• {"endpoint_text":"- Change from baseline in PGA Time Frame: Up to Month 24","definition_or_measurement_approach":"Change from baseline in Physician Global Assessment (PGA) measured up to Month 24."}
• {"endpoint_text":"- Change from baseline in FACIT-Fatigue score Time Frame: Up to Month 24","definition_or_measurement_approach":"Change from baseline in FACIT-Fatigue score measured up to Month 24."}
• {"endpoint_text":"- Change from baseline in HAQ-DI Time Frame: Up to Month 24","definition_or_measurement_approach":"Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) measured up to Month 24."}
• {"endpoint_text":"- Change from baseline in SF-36 Time Frame: Up to Month 24","definition_or_measurement_approach":"Change from baseline in SF-36 measured up to Month 24."}
• {"endpoint_text":"- Change from baseline in EQ-5D Time Frame: Up to Month 24","definition_or_measurement_approach":"Change from baseline in EQ-5D measured up to Month 24."}
• {"endpoint_text":"- Frequency and duration of hospitalization and/or critical care support to manage obe-cel-related toxicity Time Frame: Up to Month 24","definition_or_measurement_approach":"Frequency and duration of hospitalisation/critical care for obe-cel-related toxicity assessed up to Month 24."}
• {"endpoint_text":"- Frequency, severity and duration of CRS, ICANS, and other identified risks Time Frame: Up to Month 24","definition_or_measurement_approach":"Frequency, severity and duration of cytokine release syndrome (CRS), ICANS and other identified risks assessed up to Month 24."}
• {"endpoint_text":"- Adverse event (AE) type, frequency, severity, and relationship with obe-cel or lymphodepletion, safety laboratory samples, vital signs Time Frame: Up to Month 24","definition_or_measurement_approach":"AE types, frequency, severity and relationship to obe-cel or lymphodepletion; safety labs and vital signs assessed up to Month 24."}
• {"endpoint_text":"- Detection of CAR T cells Time Frame: 9 timepoints post-infusion between Days 1 and 28, followed by Month 2, Month 3, then 3-monthly to month 24","definition_or_measurement_approach":"Detection of CAR T cells at specified timepoints: 9 timepoints Days 1–28, Month 2, Month 3, then every 3 months to Month 24."}
• {"endpoint_text":"- Change from baseline in serum autoantibody concentration (antinuclear antibody [ANA], anti-double stranded DNA [anti-dsDNA], anti-Smith, anti-RNA binding protein [anti-RBP]) Time Frame: 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","definition_or_measurement_approach":"Change in serum autoantibody concentrations (ANA, anti-dsDNA, anti-Smith, anti-RBP) measured at Day -6 pre-infusion, Day 28, Month 3, then 3‑monthly to Month 12 and 6‑monthly to Month 24."}
• {"endpoint_text":"- Change from baseline in the complement panel (complement, total [CH50], C3, C4) Time Frame: 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","definition_or_measurement_approach":"Change in complement panel (CH50, C3, C4) measured at Day -6 pre-infusion, Day 28, Month 3, then 3‑monthly to Month 12 and 6‑monthly to Month 24."}
• {"endpoint_text":"- Change from baseline in PtGA Time Frame: Up to Month 24","definition_or_measurement_approach":"Change from baseline in Patient Global Assessment (PtGA) measured up to Month 24."}
• {"endpoint_text":"- Detection of B cells in the peripheral blood over time Time Frame: 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","definition_or_measurement_approach":"Detection and kinetics of peripheral B cells measured at screening/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."}
• {"endpoint_text":"- Change from baseline in the antiphospholipid profile (lupus anticoagulant, anticardiolipin antibodies and beta-2 glycoprotein) Time Frame: 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","definition_or_measurement_approach":"Change in antiphospholipid profile (lupus anticoagulant, anticardiolipin, beta-2 glycoprotein) measured at Day -6 pre-infusion, Day 28, Month 3, then 3‑monthly to Month 12 and 6‑monthly to Month 24."}

Greece

Earliest CTIS Part Ii Submission Date

07-08-2025

Latest Decision Or Authorization Date

20-11-2025

Processing Time Days

105

Number Of Sites

2

Number Of Participants

3

Primary sponsor

Full Name

Autolus Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Third parties

• {"country":"United Kingdom","full_name":"TMC Pharma Services Limited","duties_or_roles":"code:8","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"PPD (UK) Limited","duties_or_roles":"codes:1,11,12,13,2,5,6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Crisalis LLC","duties_or_roles":"code:15; Efficacy Assessment Tool Training","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"code:15; Patient transport and reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Deltamed Solutions Inc.","duties_or_roles":"code:10","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"BioAgilytix Europe GmbH","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"codes:1,12,5","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"code:7","organisation_type":"Pharmaceutical company"}