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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

• Proportion of participants achieving remission per Definition of Remission in SLE (DORIS) criteria [Срок оценки: Month 6]
• Proportion of participants achieving CRR over time [Срок оценки: Up to Month 24]
• Time to CRR [Срок оценки: Up to Month 24]
• Proportion of participants with Partial Renal Response (PRR) [Срок оценки: Up to Month 24]
• Time to PRR [Срок оценки: Up to Month 24]
• Proportion of participants achieving remission per DORIS criteria over time [Срок оценки: Up to Month 24]
• Time to achieving remission per DORIS criteria [Срок оценки: Up to Month 24]
• Time to renal flare [Срок оценки: Up to Month 24]
• Proportion of participants achieving Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 0 over time [Срок оценки: Up to Month 24]
• Proportion of participants achieving Lupus Low Disease Activity State (LLDAS) over time [Срок оценки: Up to Month 24]
• Time to LLDAS [Срок оценки: 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 [Срок оценки: Up to Month 24]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Великобритания · 8 центров

• 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

США · 3 центра

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

Греция · 2 центра

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

Бразилия · 1 центр

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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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