Exploratory Clinical Study of CNCT19 Anti CD19 Cell Therapy in the Treatment of Refractory Autoimmune Diseases

NCT06316791 | Recruiting Early Phase 1

• 1 other identifier: HY001007
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Exploratory clinical study of CNCT19 anti CD19 cell therapy in the treatment of refractory autoimmune diseases,To evaluate the safety and tolerability of CNCT19 in patients with refractory systemic lupus erythematosus (lupus nephritis, immune thrombocytopenia), refractory ANCA-associated vasculitis, and refractory dermatomyositis on the basis of standard of care.

Conditions

Lupus Erythematosus, Systemic

Keywords

CNCT19; CD19-directed CAR-T cells

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects Experiencing Treatment-Emergent Adverse Events（TEAE）

  Evaluate the type, frequency, severity of adverse events, and abnormal laboratory test values; Evaluate the frequency and severity of adverse events related to CNCT19.

  Up to 1 year after CNCT19 infusion

Secondary Outcomes (7)

• Overall survival (OS)

  Up to 1 year after CNCT19 infusion

• SELENA-SLEDAI

  Up to 1 year after CNCT19 infusion

• The proportion of subjects who achieved glucocorticoids/immunosuppressant free and subjects who achieved low-dose glucocorticoids application during the main study period

  Up to 1 year after CNCT19 infusion

• To evaluate disease related biomarkers

  Up to 1 year after CNCT19 infusion

• To evaluate disease related biomarkers

  Up to 1 year after CNCT19 infusion

Study Arms (1)

Single dose of CNCT19

EXPERIMENTAL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered before the investigational treatment, CNCT19.

Biological: single dose of CNCT19

Interventions

single dose of CNCT19 BIOLOGICAL

Autologous 2nd generation CD19-directed CAR-T cells, infusion intravenously.

Single dose of CNCT19

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The enrolled subjects or their legal representatives signed informed consent form;
• age range: 18-70 years (including 18 and 70 years), male or female;
• Subjects with refractory systemic lupus erythematosus (lupus nephritis, immune thrombocytopenia) : Diagnosed with systemic lupus erythematosus according to American College of Rheumatology (ACR) criteria, accompanied by lupus nephritis (SLE-LN) or immune thrombocytopenia (SLE-ITP) and receiving standard treatment;
• Subjects with Refractory Systemic Lupus Erythematosus (Lupus Nephritis): Active and biopsy-confirmed proliferative lupus nephritis grade III or IV or simple grade V alone according to 2003 ISN/RPS criteria. Active renal disease was defined as a urine protein: creatinine ratio \> 1.0 or proteinuria \> 3.5 grams/day.
• Subjects with refractory systemic lupus erythematosus (thrombocytopenia): At least two consecutive blood routine examinations showed that platelet was lower than 50x109/L; Blood cell morphology of peripheral blood smear was normal. The spleen is generally not enlarged; The morphological characteristics of bone marrow cells were megakaryocytic increase or normal, accompanied by maturation disorder. Platelet count \> 10 x10\^9 / L.
• Subjects with refractory ANCA-associated vasculitis: diagnosis of ANCA glomerulonephritis (GN) or vasculitis based on the 2013 American Chapel Hill Consensus Conference definition of AAV ;
• Relapsed or refractory AAV requiring treatment with cyclophosphamide or rituximab
• Newly diagnosed or recurrent AAV--, defined as accumulation of at least one major organ (e.g., kidney, lung, heart) requiring induction therapy with cyclophosphamide or rituximab;
• Anti-PR3 or anti-MPO positive (current or history);
• Subjects with Refractory Dermatomyositis: Refractory MDA5-positive dermatomyositis is defined as active disease and meets the following conditions: adequate corticosteroid therapy (greater than two to four weeks of conventional corticosteroid therapy or intolerance to such therapy) and/or
• Use of ≥ 1 conventional immunosuppressive agent (eg, methotrexate, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil, IVIG, anti-TNF, or rituximab) at a reasonable dose and duration (greater than two to four weeks or intolerance to therapy);
• Treatment with IVIG or cyclophosphamide for two to four weeks.
• Women of childbearing potential must have a negative blood pregnancy test 7 days prior to trial conditioning therapy; any male and female patients of childbearing potential must agree to use an effective method of contraception throughout the study and for at least 1 year following reinfusion of CNCT19 CAR-T cells. Childbearing potential, in the judgment of the investigator, is biologically capable of bearing a living baby and sexually active. Female patients who were not of childbearing potential (ie, met at least 1 of the following criteria):
• Hysterectomy or oophorectomy, or
• Medically confirmed ovarian failure, or medically confirmed postmenopausal (cessation of menses for at least 12 consecutive months in the absence of pathological or physiological causes).

You may not qualify if:

• Patients with severe active central nervous system (CNS) lupus, including seizures, psychosis, cerebrovascular accident or CNS vasculitis requiring therapeutic intervention within 60 days after baseline;
• Dialysis patients;
• Pregnancy or lactation;
• Concomitant uncontrollable infection (e.g., sepsis, bacteremia, fungemia, uncontrolled pulmonary infection, etc.);
• Hepatitis B surface antigen (HBsAg) positive and hepatitis C (HCV) antibody positive, human immunodeficiency virus (HIV) antibody positive, syphilis (TP) positive;
• Major surgery that was assessed as unsuitable by the investigator within 4 weeks before screening;
• Patient's heart meets any of the following:
• Left ventricular ejection fraction (LVEF) ≤ 45%;
• New York Heart Association (NYHA) Class III or IV congestive heart failure or active cardiac disease;
• Serious arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia);
• QTc interval ≥ 450 ms for males and ≥ 470 ms for females (QTcB = QT/RR1/2);
• Myocardial infarction, bypass surgery or stent surgery within 6 months prior to the study;
• Other cardiac diseases that are not suitable for the study as judged by the investigator;
• Received live vaccine within 6 weeks prior to screening.
• Participation in other interventional clinical studies within 3 months prior to cell infusion, treatment with an active experimental drug, or intentional participation in another clinical trial or treatment outside of that specified by the protocol throughout the study period.

Sponsors & Collaborators

• Juventas Cell Therapy Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Yi Zhang

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

• Shengyun Liu

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruijiao Huang

CONTACT

+86-010-65960098; huangruijiao@juventas.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 18, 2024
• Study Start: December 14, 2021
• Primary Completion: December 13, 2025
• Study Completion: December 13, 2025
• Last Updated: February 10, 2025

Record last verified: 2025-02

Locations

CN (1)