Overview
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 trial includes only 1 group of patients (single arm), including adolescent and adult patients aged 12 to 65 years. The objective is to look for benefits of obe-cel in making signs of LN completely disappear (remission) at 6 months after obe-cel treatment in patients with severe, active LN. The trial 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. The trial will also assess how long obe-cel stays in the body and the safety of obe-cel.
Description
This is a Phase 2 study to determine the efficacy and safety of obe-cel in participants with severe, refractory SLE with active LN.
The study comprises 3 periods:
- Screening Period: From Day -30 to Day of Enrolment
- Treatment Period: From Day -8 to Day 1 - Patients will be evaluated to confirm eligibility for lymphodepletion, and thereafter receive lymphodepletion to enhance treatment efficacy and cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cell survival. Obe-cel Administration: If the participant's eligibility for receiving obe-cel infusion is confirmed, the participant is to receive a single obe-cel infusion on Day 1.
- Post-treatment Period: From Day 1 to End of Study all participants will be followed up for efficacy and safety evaluation.
The primary objective is to look for benefits of obe-cel in making signs of LN completely disappear (remission) at 6 months after treatment.
Eligibility
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 Schedule of Activities and other requirements
- Participants must be 12 to 65 years of age inclusive at the time of signing the informed consent.
- 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), or anti-dsDNA or anti-Smith.
- Severe, Active SLE defined as:
- Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥ 8 points AND
- Severe active LN based on a renal biopsy obtained within 6 months prior to signing the informed consent form or during the screening period Class III, IV or V (V only in combination with class III or IV)
- Refractory SLE defined as failure to early lines of therapy and to Calcineurin inhibitors AND B cell-targeting agents
Exclusion Criteria:
- Any medications prohibited by the protocol.
- Prior treatment at any time with anti-CD19 therapy.
- More than 1 acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible.
- 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.
- History of primary antiphospholipid antibody syndrome.
- Active or uncontrolled fungal, bacterial, or viral infection
- History of malignant neoplasms unless disease free for at least 24 months.
- History of heart, lung, renal, liver transplant or hematopoietic stem cell transplant.
