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

Autolus

Status and phase

Not yet enrolling

Phase 2

Conditions

Lupus Nephritis

Treatments

Biological: Obecabtagene autoleucel

Study type

Interventional

Funder types

Industry

Identifiers

NCT07053800

1011415 (Other Identifier)

AUTO1-SL2

2024-519941-32 (EudraCT Number)

Details and patient eligibility

About

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 teenage 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 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.

Full description

This is a Phase II 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. From Day 1 to End of Study all participants will be followed up for efficacy and safety evaluation.

The objective is to look for benefits of obe cel in making signs of LN completely disappear (remission) at 6 months after treatment.

Enrollment

35 estimated patients

Sex

All

Ages

12 to 65 years old

Volunteers

No Healthy Volunteers

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.