Safety and Efficacy Study of RXIM002 in Severe, Relapsed or Refractory Autoimmune Diseases

Официальное название

A Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the CD19-Targeting Circular RNA Product RXIM002 in Patients With Relapsed or Refractory B Cell-Mediated Autoimmune Diseases

Обзор

This Phase 1, open-label study evaluates the safety, tolerability, and preliminary efficacy of RXIM002, a CD19-targeting circular RNA-mediated in-vivo CAR T-cell therapy, in adults with severe, relapsed, or refractory B cell-mediated autoimmune diseases.

Подробное описание

This Phase 1, open-label, single-arm, dose-escalation study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of RXIM002 in adults with severe, relapsed, or refractory B cell-mediated autoimmune diseases. Eligible participants will receive intravenous administration of RXIM002 and will be monitored for adverse events, laboratory parameters, and other safety outcomes. The study will also explore biological activity and potential clinical responses across the enrolled autoimmune conditions. Participants will be followed for a defined period after treatment to assess longer-term safety and durability of any observed effects. The study will include the following sequential phases: screening, treatment, and follow-up.

Вмешательства

• Биопрепарат RXIM002 product
  Prior to infusion of the RXIM002 product, subjects will receive pre-medication if needed

Первичные конечные точки

• Incidence and severity of Dose-Limiting Toxicities (DLTs) [Срок оценки: 28 days after RXIM002 first infusion (Day 1)]
• Incidence and severity of treatment-emergent adverse events (TEAEs) [Срок оценки: 52 weeks after RXIM002 first infusion (Day 1)]
• CAR positive cell Cmax [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]
• CAR positive cell Tmax [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]
• CAR positive cell AUC [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]

Вторичные конечные точки (12)

• LNP (Lipid Nanoparticle) Cmax [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]
• LNP (Lipid Nanoparticle) Tmax [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]
• LNP (Lipid Nanoparticle) AUC [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]
• CircleRNA Cmax [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]
• CircleRNA Tmax [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]
• CircleRNA AUC [Срок оценки: 24 weeks after RXIM002 first infusion (Day 1)]
• Systemic Lupus Erythematosus (SLE) disease activity: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [Срок оценки: 52 weeks after RXIM002 first infusion (Day 1)]
• Systemic Sclerosis (SSc) disease activity :Modified rodnan skin score(mRSS) [Срок оценки: 52 weeks after RXIM002 first infusion (Day 1)]
• Idiopathic Inflammatory Myopathy (IIM) disease activity ：Manual muscle test-8 [Срок оценки: 52 weeks after RXIM002 first infusion (Day 1)]
• Autoimmune Hemolytic Anemia (AIHA) disease activity: Overall Hb therapeutic response [Срок оценки: 8 weeks after RXIM002 first infusion (Day 1)]
• Immune Thrombocytopenia (ITP) disease activity: Overall response of platelet increment. [Срок оценки: 8 weeks after RXIM002 first infusion (Day 1)]
• Lupus Nephritis (LN) disease activity: Proportion of subjects achieving Primary Efficacy Renal Response(PERR) [Срок оценки: 52 weeks after RXIM002 first infusion (Day 1)]

Критерии участия

Критерии включения

• Subjects voluntary agreement to provide written informed consent.
• Aged 18 to 65 years, either sex.
• Adequate organ function meeting screening criteria.
• Positive test for cluster of differentiation antigen 19 (CD19).

Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN):

• Have been diagnosed with SLE or LN before screening.
• Presence of anti-dsDNA, anti-histone, anti-chromatin, anti-Ro (anti-SS-A), anti-La (anti-SS-B), antinuclear antibody (ANA), or anti-Sm antibodies at screening.
• Active disease at screening.
• Fulfill relapsed/refractory SLE or LN conditions

Lupus Nephritis (LN) :

• Kidney biopsy result indicating LN
• Evidence of LN disease activity

Systemic Sclerosis (SSc):

• Have been diagnosed with SSc before screening.
• Antinuclear Antibody (ANA) positive at screening or prior to screening. AND, evidence of SSc disease activity.
• Fulfill relapsed/refractory SSc conditions.

Immune Thrombocytopenia (ITP):

• Have been diagnosed with refractory ITP before screening.
• Platelet count <50×10⁹/L at screening.

Idiopathic Inflammatory Myopathy (IIM):

• Have been diagnosed with IIM before screening.
• Presence of at least 1 myositis specific (MSA), associated antibody (MAA), or ANA at screening or prior to screening.
• Evidence of IIM disease activity.
• Fulfill relapsed/refractory IIM conditions.

Membranous Nephropathy (MN):

• Have been diagnosed with MN before screening.
• Active MN patients meeting screening criteria.
• Fulfill relapsed/refractory MN conditions.

Autoimmune Hemolytic Anemia (AIHA):

• Have been diagnosed with AIHA before screening.
• Active AIHA patients meeting screening criteria.
• Fulfill relapsed/refractory AIHA conditions.

Критерии исключения

• Active infections such as hepatitis and tuberculosis.
• Other autoimmune diseases.
• Serious underlying diseases such as active malignancies, uncontrolled diabetes.
• Female subjects who were pregnant, breastfeeding.
• Any uncontrolled psychiatric disorders (e.g., schizophrenia, bipolar disorder, eating disorders, major depression or anxiety disorder), as declared by the participant or reported in the medical records.

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

Китай · 1 центр

• Ruijin Hospital — Шанхай

Идентификаторы

NCT: NCT07322718 · RX-AID-CS101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗