Obe-cel in Severe, Refractory Systemic Lupus Erythematosus (SLE) With Active Lupus Nephritis (LN)

Official title

A Single-Arm, Open-Label, Phase II Study to Determine the Safety and Efficacy of Obecabtagene Autoleucel (Obe-cel) in Participants With Severe, Refractory Systemic Lupus Erythematosus With Active Lupus Nephritis

Overview

The purpose of this trial is to evaluate the efficacy and safety of obecabtagene autoleucel (obe-cel) administered once following lymphodepletion in participants with severe, refractory systemic lupus erythematosus (SLE) and active lupus nephritis (LN).

Detailed 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:

1. Screening Period: From Day -30 (+7) to Day of Enrollment 2. Treatment Period: From Day -8 to Day 1 - Participants will be evaluated to confirm eligibility for lymphodepletion, and thereafter receive lymphodepletion.

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.

Interventions

• Biological Obecabtagene autoleucel
  Obecabtagene autoleucel (obe-cel) given as a single infusion

Primary outcome measures

• Proportion of participants who achieve complete renal response (CRR) [Time frame: Month 6]

Secondary outcome measures (12)

• Proportion of participants achieving remission per Definition of Remission in SLE (DORIS) criteria [Time frame: Month 6]
• Proportion of participants achieving CRR over time [Time frame: Up to Month 24]
• Time to CRR [Time frame: Up to Month 24]
• Proportion of participants with Partial Renal Response (PRR) [Time frame: Up to Month 24]
• Time to PRR [Time frame: Up to Month 24]
• Proportion of participants achieving remission per DORIS criteria over time [Time frame: Up to Month 24]
• Time to achieving remission per DORIS criteria [Time frame: Up to Month 24]
• Time to renal flare [Time frame: Up to Month 24]
• Proportion of participants achieving Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 0 over time [Time frame: Up to Month 24]
• Proportion of participants achieving Lupus Low Disease Activity State (LLDAS) over time [Time frame: Up to Month 24]
• Time to LLDAS [Time frame: Up to Month 24]
• Time to first disease flare according to Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI-2K Flare Index (SFI) post-obe-cel infusion [Time frame: Up to Month 24]

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 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:

• SLEDAI-2K score of ≥ 8 points AND
• Severe active LN based on a renal biopsy: Class III, IV or V (V only in combination with class III or IV)
• Refractory SLE defined as failure to previous lines of therapy

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 8 centers

• Queen Elizabeth Hospital Birmingham — Birmingham
• Bristol Haematology and Oncology Centre — Bristol
• Addenbrooke's Hospital — Cambridge
• Western General Hospital Edinburgh — Edinburgh
• Queen Elizabeth University Hospital — Glasgow
• University College Hospital — London
• Great Ormond Street Hospital — London
• Manchester Royal Infirmary — Manchester

United States · 3 centers

• Icahn School of Medicine at Mount Sinai — New York
• State University of New York Upstate Medical Center (SUNY) — Syracuse
• Texas Transplant Institute — San Antonio

Greece · 2 centers

• University General Hospital ATTIKON — Athens
• University General Hospital of Patras — Pátrai

Brazil · 1 center

• Instituto D´Or de Pesquisa e Ensino - Hospital São Rafael — Salvador

Identifiers

NCT: NCT07053800 · AUTO1-SL2 · 2024-519941-32 · 1011415

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗