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

Launched by AUTOLUS LIMITED · Jun 26, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called obe-cel for people with severe lupus nephritis, a serious kidney problem caused by lupus that hasn’t improved with current treatments. Lupus nephritis happens when the immune system attacks the kidneys, and obe-cel aims to remove the harmful immune cells (called B cells) that cause this damage. The main goal of the study is to see if obe-cel can completely clear up signs of kidney inflammation six months after treatment. Researchers will also check how well the treatment works over two years, how long any improvements last, how it affects lupus activity and quality of life, and whether there are any side effects.

People who may be eligible for this trial are teenagers and adults aged 12 to 65 who have severe, active lupus nephritis that hasn’t responded well to standard medicines like hydroxychloroquine, corticosteroids, and other drugs targeting B cells. To join, participants must weigh at least 40 kg (about 88 pounds) and meet specific lupus activity criteria based on blood tests and kidney function. Before receiving obe-cel, patients will have a short course of chemotherapy to prepare their body for the treatment, followed by a single infusion of obe-cel cells. After treatment, patients will be closely monitored with regular blood and urine tests for up to two years to check how well the treatment is working and to watch for side effects. This is an early-phase trial, and only one group of patients will receive obe-cel, with both patients and doctors knowing what treatment is given. Pregnant women or those planning pregnancy, people with serious infections, certain heart or nervous system problems, or recent cancer are not eligible to participate.

Gender

ALL

Eligibility criteria

• 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