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CNCT19 Cell Injection for Refractory Systemic Lupus Erythematosus

Primary Purpose

Refractory Systemic Lupus Erythematosus, Lupus Nephritis, Immune Thrombocytopenia

Status
Enrolling by invitation
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
CNCT19 cell injection
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Systemic Lupus Erythematosus

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1. Able to sign Informed Consent Form (ICF) ; 2. Males or females 18-70(include 18 and 70) years of age; 3. Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) 1997 or European League against Rheumatism(EULAR)/ the American College of Rheumatology (ACR) 2019 criteria .Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) 1997 or European League against Rheumatism(EULAR)/ the American College of Rheumatology (ACR) 2019 criteria . Group1:Have active, biopsy-proven proliferative lupus nephritis Class III or IV, or Class V using the 2003 ISN/RPS criteria. The biopsy must be performed in the 6 months prior to the screening visit or during the screening period. Have documentation of active renal disease defined as:24h Proteinuria> 1.5 grams/day. Refractory lupus nephritis is defined as no induced remission to treatment regimens containing at least one immunosuppressant (including glucocorticoids, CTX, tacrolimus, MMF, and cyclosporine) after 3 to 6 months, accompanied by no reduction (or worsening) of proteinuria or persistent antibody positives. Group 2: Refractory thrombocytopenia: No response to treatment with at least 1 course of MP shock (1g for 3 days) or high dose of glucocorticoids (1mg/kgd equivalent dose of glucocorticoids) combined with 1 or more immunosuppressants. Before enrollment, at least 2 consecutive blood routine tests were performed to check platelets below 50×10^9/L and above 30×10^9/L. Other non-SLE causes of thrombocytopenia, such as infection, bone marrow suppression, and hypersplenism, were excluded. 4. Not pregnant or nursing. 5. Adequate organ functions indicated as: ALT and AST < 3 times of the ULN; Total bilirubin < 2mg/dL with the exception of patients with Gibert-Meulengracht syndrome, who may be included if their total bilirubin is < 3 x ULN and direct bilirubin < 1.5mg/dL ULN; An estimated glomerular filtration rate < 30 mL/min/1.73 m^2 at the screening visit Serum creatinine ≤1.5mg/dl(133umol/l); Must have a minimum level of pulmonary reserve, non-oxygenated blood oxygen saturation >95%; 6. Lymphocyte count > 0.4×10^9/L; 7. Use a small dose of glucocorticoid (dose equivalent to ≤10mg/d prednisone) for not less than 1 month (except glucocorticoid intolerance). Exclusion Criteria: 1. Severe active central nervous system (CNS) lupus, including seizures, psychosis, cerebrovascular accidents; 2. Dialysis patients or creatinine clearance rate < 30ml/min; 3. Pregnant or breast feeding; 4. Active infections (such as sepsis, bacteremia, fungemia, uncontrolled pulmonary infection, and active tuberculosis); 5. One of the following: HBsAg positive HCV-Ab positive HIV positive TP positive 6. Undergone major surgery assessed by the subjects as unsuitable for inclusion within 4 weeks prior to screening. 7. Had or is currently suffering from other malignant tumors within five years prior to screening, except for curable tumors with negligible risk of metastasis or death, such as cervical carcinoma in situ and skin basal cell carcinoma with adequate treatment; 8. The heart meets any of the following conditions: Left ventricular ejection fraction (LVEF) ≤45%; New York Heart Association (NYHA) Class III or IV congestive heart failure or active heart disease; Severe arrhythmias requiring treatment (except atrial fibrillation and paroxysmal supraventricular tachycardia); QTcB interval male ≥450ms, female ≥470ms (QTcB=QT/RR^1/2); Had a myocardial infarction, bypass, or stent surgery within the 6 months prior to the study; Other heart diseases that the investigators judged unsuitable for inclusion; 9. Received live vaccine within 6 weeks prior to screening; 10. Participants who have participated in other interventional clinical studies within the 3 months prior to cell transfusion, received active investigational drug therapy, or who intend to participate in another clinical trial or receive treatment outside the protocol during the entire study period. 11. a history of epilepsy or other active central nervous system diseases; 12. Subjects who are known to have hypersensitivity to the ingredients of the preparation used in the test; 13. Previously received CAR T cell therapy; 14. Other conditions deemed unsuitable for participation in this clinical trial by subject.

Sites / Locations

  • Xiaofeng Zeng

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CNCT19 cell injetion

Arm Description

CNCT19 administration:0.25 to 0.5 x 10^8 CAR-positive viable

Outcomes

Primary Outcome Measures

Adverse events

Secondary Outcome Measures

Full Information

First Posted
June 24, 2023
Last Updated
July 3, 2023
Sponsor
Peking Union Medical College Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05930314
Brief Title
CNCT19 Cell Injection for Refractory Systemic Lupus Erythematosus
Official Title
CNCT19 Cell Injection for Refractory Systemic Lupus Erythematosus
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
June 19, 2023 (Actual)
Primary Completion Date
May 30, 2024 (Anticipated)
Study Completion Date
May 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Investigator-initiated, single-arm, open-label, single dose clinical study to evaluate the safety and preliminary efficacy of CNCT19 in treatment of patients with refractory systemic lupus erythematosus(SLE) presented with active lupus nephritis or active immune thrombocytopenia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Systemic Lupus Erythematosus, Lupus Nephritis, Immune Thrombocytopenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
refractory systemic lupus erythematosus(SLE) presented with active lupus nephritis or active immune thrombocytopenia.
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CNCT19 cell injetion
Arm Type
Experimental
Arm Description
CNCT19 administration:0.25 to 0.5 x 10^8 CAR-positive viable
Intervention Type
Drug
Intervention Name(s)
CNCT19 cell injection
Intervention Description
Leukapheresis and manufacturing of CNCT19: enrolled subjects will undergo a leukapheresis to target a yield of > 1x 10^9 mononuclear cells Lymphodepleting chemotherapy i. Fludarabine 25 to 30 mg/m2, once daily for 3 days ii. Cyclophosphamide 500 mg/m2, once daily for 3 days CNCT19 administration i. 0.25 to 0.5 x 10^8 CAR-positive viable T cells
Primary Outcome Measure Information:
Title
Adverse events
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Able to sign Informed Consent Form (ICF) ; 2. Males or females 18-70(include 18 and 70) years of age; 3. Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) 1997 or European League against Rheumatism(EULAR)/ the American College of Rheumatology (ACR) 2019 criteria .Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) 1997 or European League against Rheumatism(EULAR)/ the American College of Rheumatology (ACR) 2019 criteria . Group1:Have active, biopsy-proven proliferative lupus nephritis Class III or IV, or Class V using the 2003 ISN/RPS criteria. The biopsy must be performed in the 6 months prior to the screening visit or during the screening period. Have documentation of active renal disease defined as:24h Proteinuria> 1.5 grams/day. Refractory lupus nephritis is defined as no induced remission to treatment regimens containing at least one immunosuppressant (including glucocorticoids, CTX, tacrolimus, MMF, and cyclosporine) after 3 to 6 months, accompanied by no reduction (or worsening) of proteinuria or persistent antibody positives. Group 2: Refractory thrombocytopenia: No response to treatment with at least 1 course of MP shock (1g for 3 days) or high dose of glucocorticoids (1mg/kgd equivalent dose of glucocorticoids) combined with 1 or more immunosuppressants. Before enrollment, at least 2 consecutive blood routine tests were performed to check platelets below 50×10^9/L and above 30×10^9/L. Other non-SLE causes of thrombocytopenia, such as infection, bone marrow suppression, and hypersplenism, were excluded. 4. Not pregnant or nursing. 5. Adequate organ functions indicated as: ALT and AST < 3 times of the ULN; Total bilirubin < 2mg/dL with the exception of patients with Gibert-Meulengracht syndrome, who may be included if their total bilirubin is < 3 x ULN and direct bilirubin < 1.5mg/dL ULN; An estimated glomerular filtration rate < 30 mL/min/1.73 m^2 at the screening visit Serum creatinine ≤1.5mg/dl(133umol/l); Must have a minimum level of pulmonary reserve, non-oxygenated blood oxygen saturation >95%; 6. Lymphocyte count > 0.4×10^9/L; 7. Use a small dose of glucocorticoid (dose equivalent to ≤10mg/d prednisone) for not less than 1 month (except glucocorticoid intolerance). Exclusion Criteria: 1. Severe active central nervous system (CNS) lupus, including seizures, psychosis, cerebrovascular accidents; 2. Dialysis patients or creatinine clearance rate < 30ml/min; 3. Pregnant or breast feeding; 4. Active infections (such as sepsis, bacteremia, fungemia, uncontrolled pulmonary infection, and active tuberculosis); 5. One of the following: HBsAg positive HCV-Ab positive HIV positive TP positive 6. Undergone major surgery assessed by the subjects as unsuitable for inclusion within 4 weeks prior to screening. 7. Had or is currently suffering from other malignant tumors within five years prior to screening, except for curable tumors with negligible risk of metastasis or death, such as cervical carcinoma in situ and skin basal cell carcinoma with adequate treatment; 8. The heart meets any of the following conditions: Left ventricular ejection fraction (LVEF) ≤45%; New York Heart Association (NYHA) Class III or IV congestive heart failure or active heart disease; Severe arrhythmias requiring treatment (except atrial fibrillation and paroxysmal supraventricular tachycardia); QTcB interval male ≥450ms, female ≥470ms (QTcB=QT/RR^1/2); Had a myocardial infarction, bypass, or stent surgery within the 6 months prior to the study; Other heart diseases that the investigators judged unsuitable for inclusion; 9. Received live vaccine within 6 weeks prior to screening; 10. Participants who have participated in other interventional clinical studies within the 3 months prior to cell transfusion, received active investigational drug therapy, or who intend to participate in another clinical trial or receive treatment outside the protocol during the entire study period. 11. a history of epilepsy or other active central nervous system diseases; 12. Subjects who are known to have hypersensitivity to the ingredients of the preparation used in the test; 13. Previously received CAR T cell therapy; 14. Other conditions deemed unsuitable for participation in this clinical trial by subject.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaofeng Zeng, Dr
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Daobin Zhou, Dr
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Xiaofeng Zeng
City
Peking
Country
China

12. IPD Sharing Statement

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CNCT19 Cell Injection for Refractory Systemic Lupus Erythematosus

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