A Single-Arm, Open-Label, Phase Ii Study to Determine the Safety and Efficacy of Obecabtagene Autoleucel (Obe-Cel) in Participants with Severe, Refractory Systemic Lupus Erythematosus with Active Lupus Nephritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Autolus Limited

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-11-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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

Secondary objectives 6

1. 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
2. To evaluate the efficacy of obe-cel using measures of disease activity and remission
3. To evaluate the impact of obe-cel using measures of impact of treatment from the participant/physician perspective
4. To evaluate Healthcare Resources Utilization (HCRU) after treatment with obe-cel
5. To evaluate safety of obe cel
6. To evaluate the pharmacokinetics (PK) and indicators of autoimmunity

Conditions and MedDRA coding

Systemic Lupus Erythematosus with Active Lupus Nephritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 21

1. 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.
2. Recurrent neuropsychiatric lupus at any point prior to screening, or active, severe, or unstable neuropsychiatric lupus within 1 year from screening.
3. 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).
4. 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.
5. 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.
6. Diagnosis of clinically significant uveitis.
7. History or presence of severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.
8. History or presence of antiphospholipid antibody syndrome.
9. 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.
10. 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.
11. Active or latent hepatitis B or active hepatitis C.
12. History of heart, lung, renal, liver transplant or hematopoietic stem cell transplant.
13. Human immunodeficiency virus, human T-lymphotropic virus 1 or 2, or syphilis-positive test at screening.
14. 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).
15. Planning pregnancy, pregnant, or lactating.
16. 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
17. Left ventricular ejection fraction < 45% (or < institute’s lower limit of normal) confirmed by echocardiogram (ECHO).
18. Oxygen saturation (SpO2)< 90% in the absence of oxygen support.
19. 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).
20. History of anaphylactic or severe systemic reaction to fludarabine, cyclophosphamide or any of their metabolites.
21. Any other investigational treatments must have had a wash out of at least 5 half-lives.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 26

1. Remission rate as specified by DORIS Time Frame: Month 6
2. Proportion of participants with CRR. Time Frame: Up to Month 24
3. Time to CRR. Time Frame: Up to Month 24
4. Duration of CRR. Time Frame: Up to Month 24
5. Proportion of participants with PRR, defined as: • ≥ 50% reduction in UPCR from baseline Time Frame: Up to Month 24
6. Time to PRR. Time Frame: Up to Month 24
7. Duration of PRR. Time Frame: Up to Month 24
8. Remission over time, time to response, as specified by DORIS Time Frame: Up to Month 24
9. 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
10. SLEDAI-2K score over time and proportion of participants achieving SLEDAI-2K score of 0. Time Frame: Up to Month 24
11. 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
12. 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
13. Change from baseline in PGA Time Frame: Up to Month 24
14. Change from baseline in FACIT-Fatigue score Time Frame: Up to Month 24
15. Change from baseline in HAQ-DI Time Frame: Up to Month 24
16. Change from baseline in SF-36 Time Frame: Up to Month 24
17. Change from baseline in EQ-5D Time Frame: Up to Month 24
18. Frequency and duration of hospitalization and/or critical care support to manage obe-cel-related toxicity Time Frame: Up to Month 24
19. Frequency, severity and duration of CRS, ICANS, and other identified risks Time Frame: Up to Month 24
20. Adverse event (AE) type, frequency, severity, and relationship with obe-cel or lymphodepletion, safety laboratory samples, vital signs Time Frame: Up to Month 24
21. 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
22. 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
23. 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
24. Change from baseline in PtGA Time Frame: Up to Month 24
25. 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
26. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Autolus Limited

Sponsor organisation

Autolus Limited

Address

191 Wood Lane

City

London

Postcode

W12 7FP

Country

United Kingdom

Scientific contact point

Organisation

Autolus Limited

Contact name

Didem Crosby

Public contact point

Organisation

Autolus Limited

Contact name

Didem Crosby

Third parties 9

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications