Progressive Multiple Sclerosis (PMS), Relapsed/Refractory IgG4-Related Disease (r/r IgG4-RD), Relapsed/Refractory Myasthenia Gravis(r/r MS), Relapsed/Refractory Systemic Lupus Erythematosus (r/r SLE)
Conditions
Keywords
Relapsed/Refractory autoimmune diseases
Brief summary
This is a prospective, single-arm, open-label dose-escalation clinical study to evaluate LVIVO-TaVec400 in the treatment of relapsed/refractory autoimmune diseases.
Detailed description
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).
Interventions
BIOLOGICALLVIVO-TaVec400 product
Each subject will be given a single-dose LVIVO-TaVec400 via intravenous infusion.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Nanjing Legend Biotech Co.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Dose regimen finding | Maximum 104 weeks after LVIVO-TaVec400 infusion (Day 1) | Determine the Recommended Dose regimen established through dose exploratory. |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
Countries
China
Contacts
CONTACTQiubai Li, Professor
CONTACTXiangxue Meng
PRINCIPAL_INVESTIGATORQiubai Li
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed