CD19 targeted CAR T cell therapy for severe lupus
A Single-Arm, Open-Label, Phase I Study to Determine the Safety, Tolerability and Preliminary Efficacy of Obecabtagene Autoleucel in Patients With Severe, Refractory Systemic Lupus Erythematosus
This study is testing a new CAR T cell therapy to see if it can help people with severe lupus who haven't responded to other treatments.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 12 Years and up |
| Sex | All |
| Sponsor | Autolus Limited Industry-sponsored |
| Drugs / interventions | CAR T, chimeric antigen receptor |
| Locations | 6 sites (Barcelona and 5 other locations) |
| Trial ID | NCT06333483 on ClinicalTrials.gov |
What this trial studies
This Phase I study evaluates the safety, tolerability, and preliminary efficacy of obecabtagene autoleucel (obe-cel), a CAR T cell therapy targeting CD19, in patients with severe, refractory systemic lupus erythematosus (SLE). The study will enroll up to 12 patients and utilize a single-arm, open-label design to assess the treatment's pharmacokinetics and safety profile. A Bayesian Optimal Interval (BOIN) design will be employed for overdose control, with recommendations from a Safety Review Committee and Independent Data Monitoring Committee guiding dose selection for future studies.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of severe, refractory SLE and specific autoantibody positivity.
Not a fit: Patients who have previously received anti-CD19 therapy or other specific immunotherapies may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a new treatment option for patients suffering from severe, refractory systemic lupus erythematosus.
How similar studies have performed: While CAR T cell therapies have shown promise in hematological malignancies, this application in systemic lupus erythematosus is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
-Key Inclusion Criteria-
* Women or men ≥ 18 years at screening \[Spain only\] or patients 12 to 65 years of age (inclusive) at the time of signing the informed consent \[UK only\]
* 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 one 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 \[ULN\]), anti-histone or anti-chromatin (\> ULN)
* Severe, refractory SLE
Exclusion Criteria:
-Key Exclusion Criteria-
* Medications
* Within 2 months of leukapheresis: use of anti-CD20 therapy
* Prior treatment with anti-CD19 therapy (including bispecifics), adoptive T cell therapy or any prior gene therapy product (e.g., CAR T cell therapy)
* Immunization with a live or attenuated vaccine within 2 months of leukapheresis
* SLE and Autoimmunity:
* Recurrent neuropsychiatric lupus or active, severe or unstable neuropsychiatric lupus within 2 years from screening
* Diagnosis of drug-induced SLE rather than idiopathic SLE
* Any acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible; thus, making the patient ineligible for CD19 CAR T therapy as judged by the Investigator or Sponsor
* 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 patient
* Diagnosis of another non-SLE autoimmune disease (e.g., dermatomyositis, polymyositis, scleroderma, rheumatoid arthritis) or overlap syndrome
* Medical History:
* 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
* History or presence of severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis
* 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 patient has a pacemaker) or a recent (within 12 months of screening) cardiac event
* Active or uncontrolled fungal, bacterial, viral (including COVID-19), or other infection requiring systemic antimicrobials for management
* Active or latent hepatitis B or active hepatitis C
* Human immunodeficiency virus, human T-cell leukemia virus (HTLV)-1, HTLV-2 or syphilis positive test at screening
* 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, kidney, liver transplant or hematopoietic stem cell transplant
* Pregnancy or lactating
* Laboratory and Organ Function:
* Left ventricular ejection fraction \< 45% (or \< institute's lower limit of normal) confirmed by echocardiogram
* Oxygen saturation (SpO2) \< 90% in the absence of oxygen support
* B cell aplasia
Where this trial is running
Barcelona and 5 other locations
- Hospital Universitari Vall Hebrón — Barcelona, Spain (Recruiting)
- Hospital Universitari i Politecnic La Fe — Valencia, Spain (Recruiting)
- Addenbrookes Hospital — Cambridge, United Kingdom (Recruiting)
- University College London Hospitals NHS Foundation Trust — London, United Kingdom (Recruiting)
- Great Ormond Street Hospital — London, United Kingdom (Recruiting)
- Manchester Royal Infirmary, Manchester University NHS Foundation Trust, — Manchester, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Autolus Limited
- Email: clinicaltrials@autolus.com
- Phone: +44 (0) 203 911 4385
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.