Safety of PiggyBac Transposon CAR T-cells Targeting CD-19 in Refractory Lupus.

Safety/Phase I Study of PiggyBac Transposon Mediated Chimeric Antigen Receptor T Cells Targeting CD-19 in Thai Patients With Refractory Systemic Lupus Erythematosus

A Phase 1 clinical trial to evaluate the safety and efficacy of PiggyBac transposon-mediated Chimeric Antigen Receptor(CAR) T-cells targeting CD19 in refractory Systemic Lupus Erythematosus (SLE) patients who have not responded to standard immunosuppressive treatments.

Study Overview

• Status: Completed
• Conditions: SLE (Systemic Lupus)
• Intervention / Treatment: Other: PiggyBac Transposon-Mediated CD19 CAR-T Therapy

Detailed Description

This is a single-institution phase I study in adults with refractory SLE. Autologous Peripheral Blood Mononuclear Cells will be transduced with a chimeric antigen receptor targeting the B-cell surface antigen CD19 using the PiggyBac Transposon system. Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide, followed by the infusion of 1x10^6 cells/kg CD-19 CAR T-cells. Subjects will be evaluated post-treatment for toxicity, SLE disease activity, and the persistence of CAR-expressing T cells in vivo.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Please Select
    • Bangkok, Please Select, Thailand, 10330
      • King Chulalongkorn Memorial Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age between 18 and 60 years.
2. Diagnosis of Systemic Lupus Erythematosus (SLE), as defined by the American College of Rheumatology (ACR) 1997 criteria, The Systemic Lupus International Collaborating Clinics (SLICC) criteria, or the European Alliance of Associations for Rheumatology (EULAR)/ACR classification.

3. Refractory SLE, defined by one or more of the following:

   3.1 Persistently active SLE requiring ongoing maintenance therapy (if not contraindicated) with:

   • Antimalarial drug.
   • Either mycophenolate (minimum daily dose of 1500 mg) or azathioprine (minimum daily dose of 1.5 mg/kg).
   • Patients must also need a minimum daily dose of 7.5 mg prednisolone for lower disease activity maintenance, or have a SLEDAI score of 8 or higher.

   3.2 Biopsy-proven proliferative lupus nephritis after two standard induction therapies, including intravenous cyclophosphamide (cumulative dose of at least 1.5 g) and mycophenolate mofetil (administered for a minimum of 3 months), unless contraindicated.

   3.3 Worsening of biopsy-proven lupus nephritis (activity index > 6 and chronicity index < 6 within 6 months), indicated by increased proteinuria and/or decreased estimated glomerular filtration rate, despite treatment with high-dose corticosteroids (prednisolone at least 0.7 mg/kg/day or equivalent) and either mycophenolate mofetil or cyclophosphamide for a minimum of 14 days.

4. Ability to understand and willingness to sign a written informed consent document.
5. Participants of child-bearing or child-fathering potential must agree to practice birth control from enrollment until four months after receiving CAR T-cell infusion.

Exclusion Criteria:

1. Pregnant or breastfeeding women.
2. History of active malignancy, excluding non-melanoma skin cancer and carcinoma in situ (e.g., cervix, bladder, breast).
3. History of vital organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities, cirrhosis, or psychiatric illness/social situations that limit compliance with study requirements.
5. Any other clinically significant disease history or current disease that, in the judgment of the research physician, may pose a risk to the safety of the subjects or interfere with the research procedure, or the evaluation of safety and efficacy.
6. Serologic status indicating active HIV, hepatitis B, or C infection. Participants positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative PCR prior to enrollment.
7. History of severe adverse drug reaction to Cyclophosphamide or Fludarabine.
8. Received a live vaccine within 30 days prior to CAR-T cell infusion.
9. eGFR CKD-EPI < 30 ml/min/1.73m^2.
10. Participation in other clinical investigations during the study period.
11. Prior receipt of CAR-T cell therapy outside this protocol.

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: CAR T-cell therapy; Subjects will receive a conditioning lymphodepletion chemotherapy regimen consisting of fludarabine and cyclophosphamide, followed by an infusion of CD19 CAR-T cells at doses of 1 × 10⁶ cells/kg (n = 3) and 2 × 10⁶ cells/kg (n = 3).	Other: PiggyBac Transposon-Mediated CD19 CAR-T Therapy; PiggyBac Transposon-Mediated CD19 CAR-T Therapy (1-2 x 10^6 cells/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of PiggyBac transposon-mediated CAR T-cell infusion targeting CD19 in adult patients with refractory SLE.	The incidence of adverse events assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0	Up to 28 days after CD-19 CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease activity of SLE	The Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) - Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)	3, 6, and 12 months after CD-19 CAR-T cell infusion
Complete response rate of lupus nephritis	Complete response defined as normal or ≤ 25% decline of estimated glomerular filtration rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) from baseline and urinary protein to creatinine index (UPCI) or 24-hour urinary protein ≤ 0.5 g/g or g/day	3, 6, and 12 months after CD-19 CAR-T cell infusion
Partial response rate of lupus nephritis	Partial response defined as normal or ≤25% decline of eGFR CKD-EPI from baseline and at least 50% reduction of proteinuria, with a UPCI or 24-hour urinary protein between 0.5 to 3 g/g or g/day	3, 6, and 12 months after CD-19 CAR-T cell infusion

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Collaborators: King Chulalongkorn Memorial Hospital; Health Systems Research Institute,Thailand
• Investigators: Principal Investigator: Wonngarm Kittanamongkolchai, MD, Chulalongkorn University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Actual): March 1, 2026
• Study Completion (Actual): March 1, 2026

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: November 23, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: SLE-PB-CD19-CART

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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