A Clinical Study to Evaluate LVIVO-TaVec400 for the Treatment of Relapsed/Refractory Autoimmune Diseases

This is a prospective, single-arm, open-label dose-escalation and dose-expansion study, designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of the LVIVO-TaVec400, an in vivo chimeric antigen receptor (CAR) -T cell therapy in subjects with relapsed/refractory autoimmune diseases. The subject who meets the defined eligibility criteria will follow the sequential stages: screening, treatment (LVIVO-TaVec400 infusion) and follow-up (Up to 15 years).

• LVIVO-TaVec400 product (Biological): Each subject will be given a single-dose LVIVO-TaVec400 via intravenous infusion.

Primary outcomes

• The incidence of Dose-limiting toxicity (DLT) [28 days after LVIVO-TaVec400 infusion (Day 1)]: DLTs are severe adverse events refers to any untoward medical occurred in a subject participated in a clinical investigation, which has a causal relationship with the treatment and will limit the dose escalation.
• The incidence, severity of Adverse events (AEs) [Minimum 13 weeks after LVIVO-TaVec400 infusion (Day 1)]: An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment.
• The incidence, severity of Treatment-related Adverse event (TRAE) [Maximum 15 years after LVIVO-TaVec400 infusion (Day 1)]: An treatment-related adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which has a causal relationship with the treatment.
• Maximum concentration (Cmax) in peripheral blood [Maximun 5 years after LVIVO-TaVec400 infusion (Day 1)]: Maximum concentration (Cmax) in peripheral blood
• Time of maximum concentration (Tmax) in peripheral blood [Maximum 5 years after LVIVO-TaVec400 infusion (Day 1)]: Time of maximum concentration (Tmax) in peripheral blood
• Area under the concentration-time curve (AUC) in peripheral blood [Maximum 5 years after LVIVO-TaVec400 infusion (Day 1)]: Area under the concentration-time curve (AUC) in peripheral blood
• Recommended Dose regimen finding [Maximum 104 weeks after LVIVO-TaVec400 infusion (Day 1)]: Determine the Recommended Dose regimen established through dose exploratory.

Secondary outcomes

• Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores from baseline for r/r SLE subjects [Minimum 104 weeks after LVIVO-TaVec400 infusion (Day 1)]: The SLEDAI-2K scale is a cumulative index used to assess disease activity across 24 different disease descriptors in patients with SLE. A total score ranges between 0 and 105, with a higher score representing a more significant degree of disease activity.
• Change in IgG4-RD Response Index (IgG4-RD RI) from baseline for r/r IgG4-RD subjects [Minimum 104 weeks after LVIVO-TaVec400 infusion (Day 1)]: The IgG4-RD scale is a cumulative index used to assess disease activity across 25 different disease descriptions in patients with IgG4-RD. A total score ranges between 0 and 75, with a higher score representing a more significant degree of disease activity.
• Change in Expanded Disability Status Scale (EDSS) scores from baseline for PMS subjects. [Minimum 104 weeks after LVIVO-TaVec400 infusion (Day 1)]: The EDSS is a scoring system used to quantify and monitor the progression of physical disability in patients with multiple sclerosis. The total score ranges from 0 to 10, with higher scores representing a worse outcome.
• Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores from baseline for r/r MG subjects. [Minimum 104 weeks after LVIVO-TaVec400 infusion (Day 1)]: The MG-ADL is a patient-reported tool that quantifies the severity of myasthenia gravis symptoms based on daily functions. The total score ranges from 0 to 24, with higher scores representing a worse functional status.
• Change in Quantitative Myasthenia Gravis (QMG) scores from baseline for r/r MG subjects. [Minimum 104 weeks after LVIVO-TaVec400 infusion (Day 1)]: The QMG is a standard clinical tool used to quantify the severity of myasthenia gravis through objective muscle testing. The total score ranges from 0 to 39, with higher scores representing a worse clinical status.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Subjects voluntarily participate in clinical studies.
* Age 18-65 years.
* Adequate organ function at screening.
* Clinical laboratory values meet criteria at screening visit.

  r/r SLE:
* Patients meet the 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) OR 2012 Systemic lupus international collaborating clinics (SLICC) classification criteria for SLE at least 6 months before screening.
* At screening, antinuclear antibody, and/or anti-dsDNA antibody, and/or anti-Smith antibody should be positive.
* Fulfill relapsed/refractory SLE conditions.

  r/r IgG4-RD：
* Patients meet the 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for IgG4-RD.
* Fulfill relapsed/refractory IgG4-RD conditions.
* Patients have active disease: IgG4-RD Response Index (RI) ≥2.

Progressive MS：

* Diagnosis of MS according to 2017 revised McDonald criteria.
* Progressive MS according to clinical course criteria revised in 2013.
* Presence of Cerebrospinal fluid (CSF) oligoclonal bands (OCBs) or elevated IgG Index at screening.

  r/r MG：
* Diagnosis of MG.
* Myasthenia Gravis Foundation of America (MGFA) Class II-IV.
* Positive AChR-IgG or MuSK-IgG at screening.
* Fulfill refractory MG conditions.

Exclusion Criteria:

* Active infections such as hepatitis and tuberculosis.
* Coexist other autoimmune or inflammatory diseases.
* Severe underlying diseases such as tumor, uncontrolled diabetes and severe heart diseases.
* Female subjects who are pregnant, breastfeeding, or planning to become pregnant while participating in this study or within 1 year of receiving LVIVO-TaVec400 treatment.

• Qiubai Li, Principal investigator, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology