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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Prior to infusion of the RXIM002 product, subjects will receive pre-medication if needed
Ruijin Hospital
Shanghai, Huangpu District, China
RECRUITINGIncidence and severity of Dose-Limiting Toxicities (DLTs)
Time frame: 28 days after RXIM002 first infusion (Day 1)
Incidence and severity of treatment-emergent adverse events (TEAEs)
Time frame: 52 weeks after RXIM002 first infusion (Day 1)
CAR positive cell Cmax
CAR positive T cells in peripheral blood after RXIM002 infusion, maximum concentration (Cmax).
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
CAR positive cell Tmax
CAR positive T cells levels in peripheral blood after RXIM002 infusion, time to Cmax (Tmax).
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
CAR positive cell AUC
CAR positive T cells levels in peripheral blood after RXIM002 infusion, area under the concentration-time curve (AUC) .
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
LNP (Lipid Nanoparticle) Cmax
LNP in peripheral blood after RXIM002 infusion, maximum concentration (Cmax).
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
LNP (Lipid Nanoparticle) Tmax
LNP levels in peripheral blood after RXIM002 infusion, time to Cmax (Tmax)
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
LNP (Lipid Nanoparticle) AUC
LNP levels in peripheral blood after RXIM002 infusion, area under the concentration-time curve (AUC) .
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
CircleRNA Cmax
CircleRNA in peripheral blood after RXIM002 infusion, maximum concentration (Cmax).
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
CircleRNA Tmax
CircleRNA levels in peripheral blood after RXIM002 infusion, time to Cmax (Tmax).
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
CircleRNA AUC
CircleRNA levels in peripheral blood after RXIM002 infusion, area under the concentration-time curve (AUC) .
Time frame: 24 weeks after RXIM002 first infusion (Day 1)
Systemic Lupus Erythematosus (SLE) disease activity: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from baseline up to 52 weeks, a total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.
Time frame: 52 weeks after RXIM002 first infusion (Day 1)
Systemic Sclerosis (SSc) disease activity :Modified rodnan skin score(mRSS)
Change in modified Rodnan skin score (mRSS) from baseline up to 52 weeks in SSc patients. The mRSS is used to assess skin thickness and scope of SSc patients ,with a total score can fall between 0 and 51, with a higher score representing a more significant degree of skin involvement.
Time frame: 52 weeks after RXIM002 first infusion (Day 1)
Idiopathic Inflammatory Myopathy (IIM) disease activity ：Manual muscle test-8
Change in manual muscle testing (MMT-8) score from baseline up to 52 weeks in IIM patients. This tool assesses muscle strength by testing 8 proximal, distal, and axial muscles ,assess unilateral(score range 0-80 points)handedness side, with a lower score representing a more significant degree of muscle involvement.
Time frame: 52 weeks after RXIM002 first infusion (Day 1)
Autoimmune Hemolytic Anemia (AIHA) disease activity: Overall Hb therapeutic response
At least one occurrence of Hb ≥ 100 g/L, concurrently with an increase of at least 20 g/L from baseline, and not attributable to red blood cell transfusion or other emergency therapeutic drugs
Time frame: 8 weeks after RXIM002 first infusion (Day 1)
Immune Thrombocytopenia (ITP) disease activity: Overall response of platelet increment.
The proportion of subjects whose platelet count recovered to ≥ 50 × 10\^9/L and who did not require an increase in corticosteroid dose
Time frame: 8 weeks after RXIM002 first infusion (Day 1)
Lupus Nephritis (LN) disease activity: Proportion of subjects achieving Primary Efficacy Renal Response(PERR)
UPCR ≤ 0.7 g/g, with eGFR no more than 20% below the pre-lupus flare level or ≥ 60 mL/min/1.73 m², and no treatment failure event. Achieving Complete Renal Response (CRR)
Time frame: 52 weeks after RXIM002 first infusion (Day 1)
Membranous Nephropathy (MN) disease activity: Clinical remission rate
24-hour urinary protein quantification \< 3.5 g/day with serum albumin \> 30 g/L, and eGFR ≥ 85% of baseline value
Time frame: 52 weeks after RXIM002 first infusion (Day 1)