Clinical Trial of CD19-targeted CAR-T Therapy for Refractory Juvenile Dermatomyositis

Clinical Study of CD19 Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Refractory Juvenile Dermatomyositis (RJDM)

This is a Phase I clinical trial to evaluate the efficacy and safety of CD19-targeted CAR-T in the treatment of refractory juvenile dermatomyositis (RJDM).The experiment was divided into two phases: dose exploration (Part A) and dose extension (Part B).

Study Overview

• Status: Recruiting
• Conditions: Juvenile Dermatomyositis
• Intervention / Treatment: Biological: CD19-targetd CAR-T

Detailed Description

juvenile dermatomyositis (JDM) is a non-suppurative chronic autoimmune disease and the most common type of juvenile idiopathic inflammatory myopathy.Despite the active treatment measures, some JDM patients are still intolerant or unresponsive to the treatment, resulting in a high disability and mortality rate.Because CD19 is widely expressed on the surface of B lymphocytes, CD19 CAR-T can also cause deep depletion of other CD19+ B cells while killing cancer cells, which is expected to achieve immune reconstruction in patients with autoimmune diseases, and completely change the status quo that such patients need to take hormones and immunosuppressants for a long time.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Meiping Lu, M.D; Phone Number: 13685773988; Email: meipinglu@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Children's Hospital ZheJiang University School of Medicine
      • Contact: Meiping Lu, M.D; Phone Number: 13685773988; Email: meipinglu@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: ≥5 years and <17 years old
2. To meet the diagnostic criteria of JDM, four or five of the following criteria must be met:① symmetrical proximal muscle weakness; ②Characteristic skin changes, including positive dermatitis (purplish red rash on upper eyelid with periorbital edema) and Gottron papules (red patchy squamous papules on the back of knuckles); ③ The level of one muscle enzyme in serum was increased; ④ Positive myositis antibody; ⑤Electromyography shows denervation and myopathy; ⑥ Muscle biopsies showed necrosis and inflammation.
3. The classification criteria of RJDM must meet ① and any of the criteria②-④: ① Patients who are intolerant or unresponsive to glucocorticoids and at least 2 immunosuppressants, adequate hormone therapy and duration of at least 6 months; ② The disease progresses rapidly and/or involves organs such as lungs, heart and gastrointestinal tract; ③ Calcification of subcutaneous or muscle and joint tissues; ④ Repeated rashes or skin ulcers.
4. myositis specific antibody positive, defined as MDA-5, NXP2, TIF-1γ, Ro-52 and any other positive;
5. If the patient has SRP or HMGCR antibody positive immune-mediated necrotizing myopathy equivalent to RJDM, the inclusion criteria of (2) - (4) can be met.

6. The functions of important organs are basically normal:

   ① Cardiac function: left ventricular ejection fraction (LVEF) ≥55%, no obvious abnormality in electrocardiogram;

   ② Renal function: eGFR≥30ML/min/1.73m2;

   ③ Liver function: AST and ALT≤3.0 ULN, total bilirubin ≤2.0×ULN;

   ④ Lung function: Lung function is basically normal, SpO2≥92%;

7. Have the criteria for simple or intravenous blood collection, and no other contraindications for cell collection;
8. The subject of childbearing age has a negative urine pregnancy test result and agrees to take effective contraceptive measures during the test period until 1 year after the infusion;
9. The patient or his/her guardian agrees to participate in this clinical trial and signs an informed consent indicating that he/she understands the purpose and procedure of this clinical trial and is willing to participate in the study.

Exclusion Criteria:

1. Had previously received CAR T cell therapy;
2. Have other autoimmune or rheumatic diseases other than JDM;
3. primary immunodeficiency or severe secondary immunodeficiency that has not been corrected;
4. accompanied by serious infectious diseases, including but not limited to active tuberculosis, latent tuberculosis infection, active viral hepatitis, etc.;
5. Evidence of active malignant disease or diagnosis of malignant tumor (including hematological malignancies and solid tumors, except resected and cured skin basal cell carcinoma)
6. Congenital heart disease or history of acute myocardial infarction within 6 months before screening, or severe arrhythmias (including multi-source frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with a large number of pericardial effusion, serious myocarditis, etc.; Or patients with unstable vital signs who need hypertensive drugs to maintain their blood pressure;
7. suffering from other diseases that require long-term use of glucocorticoids or immunosuppressants;
8. There is an active or uncontrollable infection that requires systemic treatment within 1 week prior to screening;
9. Received solid organ transplantation or hematopoietic stem cell transplantation within 3 months before screening; Acute graft-versus-host disease (GVHD) of grade 2 or above was present within 2 weeks prior to screening;
10. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
11. Had received live vaccine within 4 weeks prior to screening;
12. Positive blood pregnancy test;
13. Patients with known malignant diseases such as tumors before screening;
14. Patients who had participated in other clinical trials within 3 months prior to enrollment;
15. Situations in which other investigators consider it inappropriate to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD19-targeted CAR-T; The experiment was divided into two phases: dose exploration (Part A) and dose extension (Part B).	Biological: CD19-targetd CAR-T; Subjects underwent lymphocyte clearance chemotherapy and then received a single intravenous cell infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of CAR-T in the treatment of refractory juvenile dermatomyositis [Safety and Tolerability]	The incidence of adverse events after CAR-T cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).including the type, frequency and severity of adverse events	28 days
To evaluate the efficacy of CAR-T in the treatment of refractory juvenile dermatomyositis [Effectiveness]	Disease improvement rate: The number of subjects who achieved disease improvement as a percentage of all subjects who received transfusions.	2month,3months
Duration of Response (DOR) of CAR-T treatment in the treatment of refractory juvenile dermatomyositis [Effectiveness]	DOR will be assessed from the first assessment of remission to the first assessment of recurrence or progression of the disease or death from any cause	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCS of CD19 CAR-T cells [Cell dynamics]	AUCS is defined as the area under the curve in 90 days	3 months
TMAX of CD19 CAR-T cells[Cell dynamics]	TMAX is defined as the time to reach the highest concentration	3 months
CMAX of CD19 CAR-T cells [Cell dynamics]	CMAX is defined as the highest concentration of CEA CAR-T cells expanded in peripheral blood	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effects of CD19-targeting CAR T cell preparations on the weight of children	Weight in kilograms were monitored after transfusion until subjects reached 18 years of age	2 years
To evaluate the effects of CD19-targeting CAR T cell preparations on the height of children	Height in meters were monitored after transfusion until subjects reached 18 years of age	2 years

Collaborators and Investigators

• Sponsor: Chongqing Precision Biotech Co., Ltd
• Investigators: Principal Investigator: Meiping Lu, M.D, Children's Hospital ZheJiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): August 26, 2024
• Last Update Submitted That Met QC Criteria: August 23, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T; CD19
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Polymyositis; Myositis; Dermatomyositis
• Other Study ID Numbers: PBC068

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No