Moderate to Severe Refractory Autoimmune Diseases
Conditions
Brief summary
This study is an open-label, single-arm, dose-escalation and dose-expansion clinical trial designed to evaluate the safety, efficacy and cellular pharmacokinetics of GT801 injection in patients with moderate to severe refractory autoimmune diseases.
Interventions
BIOLOGICALGT801 Injection
GT801 Injection
Sponsors
Vivacta Biotechnology (Shanghai) Co., Ltd.
RenJi Hospital
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
* 1.The participant or their legal representative voluntarily signs a written informed consent form and is willing and able to comply with the study procedures. * 2\. Aged 18 to 65 years old (inclusive) at the time of signing the informed consent, regardless of gender. * 3.subjects should be diagnosed with recurrent or refractory autoimmune diseases, including but not limited to systemic lupus erythematosus (SLE), lupus nephritis (LN), membranous nephropathy (MN), Idiopathic Inflammatory Myopathy (IIM), Systemic Sclerosis (SSc), ANCA-Associated Vasculitis (AAV), Sjogren's Syndrome. * 4.Organ function meets the corresponding criteria. * 5.Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result at screening and agree to avoid breastfeeding during study participation until at least 1 year after GT801 injection or until GT801 cells are no longer detectable by two consecutive flow cytometry tests, whichever is later.
Exclusion criteria
* 1\. History of severe hypersensitivity reactions or allergies. * 2\. Contraindications to or hypersensitivity reactions to any component of the investigational product. * 3\. History of the following cardiac diseases: * a. New York Heart Association (NYHA) Class III or IV congestive heart failure. * b. Myocardial infarction or coronary artery bypass grafting within 6 months prior to screening. * c. History of clinically significant ventricular arrhythmia or unexplained syncope not caused by vasovagal response or dehydration; or corrected QT interval (QTc) \> 480 ms at screening; history of severe non-ischemic cardiomyopathy. * 4\. History of any active malignancy or malignant tumor within 5 years prior to screening, except for the following conditions: early-stage tumors treated with curative intent (carcinoma in situ or Stage I tumors, non-ulcerative primary melanoma with depth \< 1 mm and no lymph node involvement), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast that has undergone potentially curative treatment. * 5\. Any other known autoimmune diseases besides the study disease. * 6\. Long-term use of anticoagulant drugs that affect coagulation function. * 7\. Clinically significant bleeding symptoms or confirmed bleeding tendency within 6 months prior to screening (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.); hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophilia, coagulation disorders, hypersplenism, etc.); arterial or venous thrombotic events within 6 months prior to screening (e.g., cerebrovascular diseases including cerebral hemorrhage and cerebral infarction, deep vein thrombosis, and/or pulmonary embolism). * 8\. Subjects with active virus infection including Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV), Hepatitis C virus (HCV), cytomegalovirus (CMV), syphilis and tuberculosis etc. * 9\. Receipt of other investigational drugs within 4 weeks prior to signing the informed consent form (ICF); or the interval between the ICF signing date and the last dose of the previous clinical trial participation is still within 5 half-lives of the drug, whichever is longer. * 10\. Receipt of plasma exchange therapy or immunoadsorption therapy within 4 weeks prior to investigational product administration. * 11\. Prior treatment with B-cell targeted therapies within 3 months prior to study drug administration (the investigator may make appropriate adjustments according to the participant's condition), including but not limited to rituximab, belimumab, telitacicept, etc. * 12\. Receipt of biologic therapy such as anti-TNF-α antibodies within 12 weeks prior to investigational product administration. * 13\. Use of tacrolimus, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate, etc., within 2 weeks prior to investigational product administration. * 14\. Receipt of neonatal Fc receptor (FcRn) antagonist therapy (e.g., efgartigimod, etc.) within 3 weeks prior to investigational product administration. * 15\. Receipt of complement inhibition therapy (e.g., eculizumab, etc.) within 3 weeks prior to investigational product administration. * 16\. Vaccination with live attenuated vaccines or mRNA vaccines within 8 weeks prior to enrollment; or inactivated vaccines within 4 weeks prior to enrollment. * 17\. Major surgery within 8 weeks prior to screening, or planned surgery during the study period. * 18\. History of organ transplantation. * 19\. Prior receipt of chimeric antigen receptor T-cell (CAR-T) therapy targeting any antigen. * 20\. Presence of any conditions that, in the investigator's judgment, would prevent the participant from completing the entire trial, confound trial results, or make trial participation not in the participant's best interest.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants experiencing dose limiting toxicity | 28 days | The proportion of participants with dose-limiting toxicity (DLT) occurring within 28 days after infusion |
| Adverse Events (AEs) occurring after infusion and their proportions | 3 months | Adverse Events (AEs) occurring after infusion and their proportions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy outcomes for Systemic Lupus Erythematosus (SLE) | 1, 2, 3 and 6 Months post GT801 infusion | SLE Response index 4(SRI-4) response: Min/Max Value: Not specified; a decrease in score indicates improvment, higher scores indicate worse outcome |
| Efficacy outcomes for lupus nephritis (LN) | 1, 2, 3 and 6 Months post GT801 infusion | Renal response rate |
| Efficacy outcomes for membranous nephropathy (MN) | 1, 2, 3 and 6 Months post GT801 infusion | Renal response rate |
| Efficacy outcomes for Idiopathic Inflammatory Myopathies (IIM) | 1, 2, 3 and 6 Months post GT801 infusion | Total lmprovement Score (TlS): Min/Max Value: Not specified; an increase in score indicates improvement, higher scores indicate better outcome. |
| Efficacy outcomes for Systemic Sclerosis (SSc) | 1, 2, 3 and 6 Months post GT801 infusion | Combined Response Index in Systemic Sclerosis (CRISS): the score ranges from 0 to 1 point; a score ≥ 0.6 indicates treatment improvement, while a score \< 0.6 indicates no disease improvement. |
| Efficacy Outcomes for ANCA-Associated Vasculitis (AAV) | 6 and 12 Months post GT801 infusion | The proportion of subjects achieving complete remission and partial remission |
| Efficacy Outcomes for Participants with Sjogren's Syndrome | 6 and 12 Months post GT801 infusion | EULAR Sjögren's Syndrome Disease Activity Index （ESSDAI）response rates |
| Cellular Kinetics of All Participants: Time to Peak Expansion of GT801 Cells After Infusion (Tmax) | From infusion to 12 months | Time to Peak Expansion (Tmax) refers to the time point at which the infused target cells proliferate to the peak quantity in the participants' bodies. |
| Cellular Kinetics of All Participants: Expansion Peak of GT801 Cells After Infusion (Cmax) | From infusion to 12 months | Expansion Peak (Cmax) refers to the maximum quantity of infused GT801 cells achieved during their proliferation in the participants' bodies. |
| Cellular Kinetics of All Participants: Area Under the Curve (AUC) of GT801 Cells After Infusion | From infusion to 12 months | Area Under the Curve (AUC) refers to the area enclosed by the curve of GT801 cell quantity change over time after infusion and the time axis. |
| Cellular Kinetics of All Participants: Duration of Detectable Concentration of GT801 Cells After Infusion (Tlast) | From infusion to 12 months | Duration of Detectable Concentration (Tlast) refers to the time period from the infusion of GT801 cells to the last time point at which the target cells can be detected in the peripheral blood or target tissues. |
| Pharmacodynamic characteristics in participants for all participants | From infusion to 2 months | Monitor serum cytokine levels after infusion |
Countries
China
Contacts
CONTACTHong Cai
Outcome results
None listed