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

Phase 2RecruitingNCT07053800

Autolus Limited35 enrolled

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.

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: 1. Screening Period: From Day -30 to Day of Enrolment 2. 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. 3. 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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 12 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

CRR is defined as change in * urine protein creatinine ratio (UPCR) and * estimated glomerular filtration rate (eGFR) and * without use of rescue medication

Time frame: Month 6

Secondary Outcomes

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

Time frame: Month 6

Proportion of participants with CRR.

CRR is defined as change in UPCR and eGFR without use of rescue medication.

Time frame: Up to Month 24

Time to CRR

CRR is defined as change in UPCR and eGFR without use of rescue medication.

Time frame: Up to Month 24

Duration of CRR.

CRR is defined as change in UPCR and eGFR without use of rescue medication.

Time frame: Up to Month 24

Proportion of participants with Partial Renal Response (PRR)

PRR is defined as reduction in UPCR from baseline.

Time frame: Up to Month 24

Remission over time as specified by DORIS.

Time frame: Up to Month 24

Time to response, as specified by DORIS.

Time frame: Up to Month 24

Remission over time, as specified by the definition of remission in Lupus Low Disease Activity State (LLDAS).

Definition as specified by LLDAS

Time frame: Up to Month 24

Time to remission and duration of remission, as specified by the definition of remission in LLDAS.

Definition as specified by LLDAS

Time frame: Up to Month 24

Time from obe-cel infusion to first disease flare according to definition of flare in Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI-2K Flare Index (SFI)

Time frame: Up to Month 24

Changes from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue

Score range 0-52. A score of less than 30 indicates severe fatigue. The higher the score, the better the quality of life.

Time frame: Up to Month 24

Changes from baseline in Disability Health Assessment Questionnaire - Disability Index (HAQ-DI).

HAQ-DI instrument consists of 2 visual analog scales 1) the Participant's Global Assessment and 2) Pain scale. Both are scored from 0-100 with higher numbers representing worse perceived disease activity or overall health.

Time frame: Up to Month 24

Changes from baseline in Short Form Health Survey (SF-36).

The SF-36 score range is from 0 to 100. Higher scores indicate better perceived health, while lower scores indicate greater disability or poorer health. The SF-36 assesses eight health domains: physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems, and mental health.

Time frame: Up to Month 24

Changes from baseline in EuroQoL (EQ)-5 Dimension (D).

EQ-5D index scores range from -0.59 to 1, where 1 is the best possible health state; EQ visual analog scale scores range from 0 to 100, where 100 is the best possible health state.

Time frame: Up to Month 24

To evaluate safety of obe-cel

Number of participants with Adverse events (AE).

Time frame: Up to Month 24

Pharmacokinetics (PK) of CAR-T cells post obe-cel infusion - Maximum concentration (Cmax)