CD19 CAR-T Therapy for Refractory Pemphigus Vulgaris (RESET-PV-CART)

A Single-Arm, Open-Label Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of CD19 CAR-T Cell Therapy in Patients With Moderate-to-Severe Refractory Pemphigus Vulgaris

This is an investigator-initiated, single-center, single-arm, open-label exploratory clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of autologous CD19 CAR-T cell therapy in patients with refractory pemphigus vulgaris.

Study Overview

• Status: Recruiting
• Conditions: Pemphigus Vulgaris
• Intervention / Treatment: Biological: Autologous CD19 CAR-T cells

Detailed Description

This is an investigator-initiated, open-label, single-center, single-arm exploratory interventional study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immune reconstitution, and preliminary clinical efficacy of autologous CD19 CAR-T cell therapy in adult patients with moderate-to-severe refractory pemphigus vulgaris.

Eligible participants are adults with refractory pemphigus vulgaris. After enrollment, participants will undergo leukapheresis for ex vivo manufacturing of autologous CD19 CAR-T cells. After product release, participants will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide within 2 to 7 days prior to CAR-T infusion.

Participants will receive a single intravenous infusion of autologous CD19 CAR-T cells at a protocol-defined dose (1 X 10^6 CAR-positive T cells per kilogram of body weight). Premedication may be administered at investigator discretion. No comparator group is included.

Participants will be followed for up to 96 weeks after infusion. Safety assessments include monitoring for cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, infections, cytopenias, organ toxicities, and other treatment-emergent adverse events.

Efficacy assessments include changes in PDAI score, disease control, Physician Global Assessment (PGA), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), relapse rate, time to relapse, and corticosteroid-sparing effects.

Translational assessments include peripheral CD19-positive B-cell depletion and reconstitution, B-cell subset dynamics, serum anti-desmoglein 1 and 3 antibody levels, and serum cytokine profiles. CAR-T pharmacokinetics will be evaluated through CAR transgene copy number and circulating CAR-positive T-cell detection, including expansion and persistence metrics.

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaoya Du; Phone Number: +86 27 8533 2028
• Study Contact Backup: Name: Jinbo Chen, MD, PhD; Phone Number: +86 188 2736 3048; Email: chen999jb@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Traditional Chinese and Western Medicine Hospital of Wuhan, Wuhan, Hubei
      • Contact: Jinbo Chen, MD+PhD; Phone Number: +86 188 2736 3048; Email: chen999jb@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Participants must meet all of the following criteria:

1. Ability to provide written informed consent.
2. Age 18 to 70 years at screening, male or female.
3. Diagnosis of pemphigus vulgaris confirmed by clinical presentation, histopathology, direct immunofluorescence (DIF), and positive anti-desmoglein 3 and/or anti-desmoglein 1 antibodies.
4. Moderate-to-severe disease activity defined as Pemphigus Disease Area Index (PDAI) ≥ 15 at screening.

5. Refractory pemphigus vulgaris is defined as inadequate response, disease relapse, or treatment dependence following systemic corticosteroids and rituximab-based therapy for at least 6 months, with persistent disease activity meeting at least one of the following criteria:

   1. Ongoing active disease with the appearance of new erythema, blisters, or erosions;
   2. Persistently elevated anti-desmoglein 1 or anti-desmoglein 3 antibody titers > 100 U/mL;
   3. Inability to taper systemic corticosteroids to < 20 mg/day prednisone equivalent (i.e., ≥ 4 tablets/day of standard prednisone dosing).
6. Requirement for systemic therapy at screening due to active disease.
7. Adequate vascular access for leukapheresis.
8. Life expectancy greater than 6 months.

9. Participants must have adequate organ function as defined below:

   1. Hematologic function: absolute neutrophil count ≥ 1.0 × 10⁹/L, platelet count ≥ 50 × 10⁹/L, hemoglobin ≥ 80 g/L.
   2. Renal function: Creatinine clearance ≥ 40 mL/min.
   3. Hepatic function: ALT and AST ≤ 2.5 × upper limit of normal; total bilirubin ≤ 1.5 × upper limit of normal.
   4. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50% with no clinically significant cardiac dysfunction.
   5. Pulmonary function: Dyspnea ≤ Grade 1 (CTCAE v5.0) and oxygen saturation (SpO₂) ≥ 92% on room air.
   6. Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × upper limit of normal, with no clinically significant coagulopathy.

9. No evidence of clinically significant active infection at baseline evaluation.

10. Reproductive Criteria: Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test within 48 hours prior to initiation of lymphodepleting chemotherapy. Women of childbearing potential must agree to use effective contraception during study participation and for at least 12 months after CAR-T infusion. Male participants must agree to use effective contraception and avoid sperm donation during study participation and for at least 12 months after infusion.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded:

1. Active uncontrolled infection at screening, requiring systemic antimicrobial therapy. Participants with active tuberculosis, hepatitis C virus (HCV), human immunodeficiency virus (HIV), or syphilis infection will be excluded. Participants with hepatitis B surface antigen and/or hepatitis B core antibody positivity may be eligible only if HBV DNA is below the lower limit of quantification and appropriate antiviral prophylaxis is provided at the investigator's discretion.
2. History of other active autoimmune disease requiring systemic immunosuppression.
3. Previous treatment with any gene-modified cellular therapy, including CAR-T or CAR-NK therapy.
4. Prior allogeneic stem cell or solid organ transplantation.
5. Severe or uncontrolled cardiovascular, pulmonary, hepatic, or renal disease that would increase risk associated with lymphodepleting chemotherapy or CAR-T cell infusion.
6. Use of high-dose systemic corticosteroids (>1 mg/kg/day prednisone equivalent) within 7 days prior to leukapheresis.
7. Use of rituximab or other B-cell-targeted biologics within protocol-defined washout period.
8. Use of intravenous immunoglobulin, plasma exchange, or other intensive immunomodulatory therapy within 2 weeks prior to leukapheresis.
9. Received live vaccine within 8 weeks prior to screening.
10. History of malignancy within 5 years prior to enrollment, except adequately treated non-melanoma skin cancer or in situ carcinoma.
11. Pregnancy or breastfeeding.
12. Known hypersensitivity to any component of lymphodepleting chemotherapy or CAR-T cell product.
13. Any condition that, in the investigator's judgment, would compromise patient safety or study integrity.

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 CAR-T Therapy for Refractory Pemphigus Vulgaris; Participants with moderate-to-severe refractory pemphigus vulgaris will undergo leukapheresis for ex vivo manufacturing of autologous CD19 CAR-T cells. The CAR-T product is individually manufactured from each participant's own peripheral blood mononuclear cells and reinfused into the same participant; therefore, this is an autologous, patient-specific cellular therapy and not an allogeneic or off-the-shelf product. Following confirmation of product release, participants will receive protocol-defined lymphodepleting chemotherapy prior to CAR-T infusion, followed by a single intravenous infusion of autologous CD19 CAR-T cells. Participants will be monitored for safety, pharmacokinetics, pharmacodynamics, immune reconstitution, and preliminary clinical efficacy.

Biological: Autologous CD19 CAR-T cells; Autologous CD19 CAR-T cells are manufactured ex vivo using the participant's own T cells collected by leukapheresis. The CAR construct targets CD19-expressing B cells and consists of a single-chain variable fragment directed against CD19. Participants will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide prior to CAR-T cell infusion according to the protocol-defined schedule. Following completion of lymphodepletion, each participant will receive a single intravenous infusion of autologous CD19 CAR-T cells under inpatient monitoring. Premedication, including acetaminophen and diphenhydramine, may be administered prior to infusion at the investigator's discretion in accordance with institutional practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Treatment-Emergent Adverse Events	Treatment-emergent adverse events, serious adverse events, dose-limiting toxicities, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, infections, cytopenias, organ toxicities, infusion-related reactions, and clinically significant laboratory abnormalities will be assessed. Adverse events will be graded according to CTCAE v5.0, and immune effector cell-related toxicities will be assessed according to applicable consensus grading criteria.	From initiation of lymphodepleting chemotherapy through Day 90 after CAR-T cell infusion
Change From Baseline in PDAI Score at Week 12	The change from baseline in Pemphigus Disease Area Index (PDAI) score at Week 12 will be assessed to evaluate preliminary clinical efficacy of autologous CD19 CAR-T cell therapy in patients with refractory pemphigus vulgaris.	Baseline and Week 12
Proportion of participants achieving disease control at Week 4 after CAR-T infusion	Disease control is defined as cessation of new active cutaneous or mucosal lesions with established lesion healing or no further progression of existing lesions, as assessed by the investigator. This endpoint evaluates the early clinical response following CD19 CAR-T cell therapy and reflects initial disease stabilization after B-cell depletion.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Pemphigus Disease Area Index （PDAI） Score Over Time (Range 0-263)	Changes from baseline in Pemphigus Disease Area Index (PDAI) score will be assessed at scheduled follow-up visits to evaluate the durability of clinical response. The total PDAI score ranges from 0 to 263, with higher scores indicating more severe disease.	Baseline through Week 96 after CAR-T cell infusion
Change From Baseline in Physician Global Assessment Score (PGA) (Range 0-10)	Change from baseline in PGA score will be assessed at scheduled follow-up visits. PGA is a physician-rated global assessment of pemphigus disease severity, with higher scores indicating more severe disease activity.	Baseline through Week 96 after CAR-T cell infusion
Change from Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) (Range 0-206)	Change from baseline in ABSIS will be assessed at scheduled follow-up visits. ABSIS is used to evaluate autoimmune bullous disease activity, with higher scores indicating more severe disease activity.	Baseline through Week 96 after CAR-T cell infusion
Proportion of participants achieving disease control at Week 12	Disease control is defined as cessation of new active cutaneous or mucosal lesions with healing or stabilization of existing lesions, as assessed by the investigator. This endpoint evaluates the durability and consolidation of clinical response following CD19 CAR-T cell therapy in patients with refractory pemphigus vulgaris.	Week 12
Change From Baseline in Anti-Desmoglein 1 and Anti-Desmoglein 3 Antibody Levels	Serum anti-desmoglein 1 and anti-desmoglein 3 antibody levels will be measured to evaluate changes in pemphigus-related autoantibody responses after CD19 CAR-T cell therapy.	Baseline through Week 96 after CAR-T cell infusion
Peripheral CD19-Positive B-Cell Depletion and Reconstitution	Peripheral CD19-positive B-cell counts and B-cell subset dynamics will be assessed to evaluate the pharmacodynamic effect of CD19 CAR-T cell therapy, including B-cell depletion, time to B-cell aplasia, duration of B-cell depletion, and B-cell reconstitution.	Baseline through Week 96 after CAR-T cell infusion
Number of Circulating CAR-Positive T Cells in Peripheral Blood	The number of circulating CAR-positive T cells in peripheral blood will be measured by flow cytometry at scheduled time points after CAR-T cell infusion to assess in vivo CAR-T cell expansion.	From CAR-T cell infusion through Week 96
CAR Transgene Copy Number in Peripheral Blood	CAR transgene copy number in peripheral blood will be measured by quantitative polymerase chain reaction or digital PCR at scheduled time points after CAR-T cell infusion to assess CAR-T cell expansion and persistence.	From CAR-T cell infusion through Week 96
Duration of Detectable CAR-T Cells in Peripheral Blood	The duration of detectable CAR-T cells in peripheral blood will be assessed based on the time from CAR-T cell infusion to the last time point at which CAR-positive T cells or CAR transgene copies remain detectable.	From CAR-T cell infusion through Week 96
Change From Baseline in Serum Cytokine Levels	Change from baseline in serum cytokine levels will be measured to characterize immune activation after CAR-T cell infusion and to support evaluation of cytokine release syndrome. Cytokines include interleukin-6 (IL-6), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-2 (IL-2), interleukin-10 (IL-10), and interleukin-17A (IL-17A).	Baseline through Week 96 after CAR-T cell infusion
Change From Baseline in Lymphocyte Subset Counts	Change from baseline in lymphocyte subset counts will be assessed at scheduled follow-up visits by flow cytometry to characterize immune reconstitution after CD19 CAR-T cell therapy. Lymphocyte subsets include CD3-positive T cells, CD4-positive T cells, CD8-positive T cells, CD19-positive B cells, and natural killer cells.	Baseline through Week 96 after CAR-T cell infusion
Change From Baseline in B-Cell Subset Counts	Change from baseline in B-cell subset counts will be assessed at scheduled follow-up visits by flow cytometry to characterize B-cell depletion and reconstitution after CD19 CAR-T cell therapy. B-cell subsets may include naïve B cells, non-switched memory B cells, switched memory B cells, and plasmablasts.	Baseline through Week 96 after CAR-T cell infusion
Relapse Rate Through Week 96	Relapse rate will be assessed as the proportion of participants who experience relapse after achieving disease control. Relapse is defined as the occurrence of three or more new lesions within one month that do not heal spontaneously within one week, or extension of established lesions.	From disease control through Week 96 after CAR-T cell infusion
Time to First Relapse	Time to first relapse will be assessed as the time from achievement of disease control to the first documented relapse.	From disease control through Week 96 after CAR-T cell infusion
Change From Baseline in Daily Prednisone-Equivalent Corticosteroid Dose	Change from baseline in daily systemic corticosteroid use will be assessed using prednisone-equivalent dose in milligrams per day at scheduled follow-up visits. A lower prednisone-equivalent daily dose indicates reduced corticosteroid requirement after CAR-T cell therapy.	Baseline through Week 96 after CAR-T cell infusion
Incidence of Serious Adverse Events and Long-Term Safety Events	Serious adverse events, infections, prolonged cytopenias, organ dysfunction, secondary malignancies, and other clinically significant long-term safety events will be recorded throughout the study follow-up period.	From informed consent through Week 96 after CAR-T cell infusion

Collaborators and Investigators

• Sponsor: Jinbo Chen

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: June 19, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin Diseases, Vesiculobullous; Skin and Connective Tissue Diseases; Pemphigus
• Other Study ID Numbers: WuhanITCWMH-XS-2025139

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