CD19 CAR-T Therapy for Refractory Pemphigus Vulgaris

NCT07681388 | Recruiting

• 1 other identifier: WuhanITCWMH-XS-2025139
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pemphigus Vulgaris

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (16)

• Change From Baseline in Pemphigus Disease Area Index （PDAI） Score Over Time (Range 0-263)

  Baseline through Week 96 after CAR-T cell infusion

• Change From Baseline in Physician Global Assessment Score (PGA) (Range 0-10)

  Baseline through Week 96 after CAR-T cell infusion

• Change from Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) (Range 0-206)

  Baseline through Week 96 after CAR-T cell infusion

• Proportion of participants achieving disease control at Week 12

  Week 12

• Change From Baseline in Anti-Desmoglein 1 and Anti-Desmoglein 3 Antibody Levels

  Baseline through Week 96 after CAR-T cell infusion

Study Arms (1)

CD19 CAR-T Therapy for Refractory Pemphigus Vulgaris

EXPERIMENTAL

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

Interventions

Autologous CD19 CAR-T cells BIOLOGICAL

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.

CD19 CAR-T Therapy for Refractory Pemphigus Vulgaris

Eligibility Criteria

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

You may qualify if:

• Participants must meet all of the following criteria:
• Ability to provide written informed consent.
• Age 18 to 70 years at screening, male or female.
• Diagnosis of pemphigus vulgaris confirmed by clinical presentation, histopathology, direct immunofluorescence (DIF), and positive anti-desmoglein 3 and/or anti-desmoglein 1 antibodies.
• Moderate-to-severe disease activity defined as Pemphigus Disease Area Index (PDAI) ≥ 15 at screening.
• 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:
• Ongoing active disease with the appearance of new erythema, blisters, or erosions;
• Persistently elevated anti-desmoglein 1 or anti-desmoglein 3 antibody titers \> 100 U/mL;
• Inability to taper systemic corticosteroids to \< 20 mg/day prednisone equivalent (i.e., ≥ 4 tablets/day of standard prednisone dosing).
• Requirement for systemic therapy at screening due to active disease.
• Adequate vascular access for leukapheresis.
• Life expectancy greater than 6 months.
• Participants must have adequate organ function as defined below:
• Hematologic function: absolute neutrophil count ≥ 1.0 × 10⁹/L, platelet count ≥ 50 × 10⁹/L, hemoglobin ≥ 80 g/L.
• Renal function: Creatinine clearance ≥ 40 mL/min.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded:
• 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.
• History of other active autoimmune disease requiring systemic immunosuppression.
• Previous treatment with any gene-modified cellular therapy, including CAR-T or CAR-NK therapy.
• Prior allogeneic stem cell or solid organ transplantation.
• Severe or uncontrolled cardiovascular, pulmonary, hepatic, or renal disease that would increase risk associated with lymphodepleting chemotherapy or CAR-T cell infusion.
• Use of high-dose systemic corticosteroids (\>1 mg/kg/day prednisone equivalent) within 7 days prior to leukapheresis.
• Use of rituximab or other B-cell-targeted biologics within protocol-defined washout period.
• Use of intravenous immunoglobulin, plasma exchange, or other intensive immunomodulatory therapy within 2 weeks prior to leukapheresis.
• Received live vaccine within 8 weeks prior to screening.
• History of malignancy within 5 years prior to enrollment, except adequately treated non-melanoma skin cancer or in situ carcinoma.
• Pregnancy or breastfeeding.
• Known hypersensitivity to any component of lymphodepleting chemotherapy or CAR-T cell product.
• Any condition that, in the investigator's judgment, would compromise patient safety or study integrity.

Sponsors & Collaborators

• Jinbo Chen: lead

Study Sites (1)

Traditional Chinese and Western Medicine Hospital of Wuhan, Wuhan, Hubei

Wuhan, Hubei, China

RECRUITING

MeSH Terms

Conditions

Pemphigus

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Jinbo Chen, MD, PhD

CONTACT

+86 188 2736 3048; chen999jb@163.com

Xiaoya Du

CONTACT

+86 27 8533 2028

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director of Dermatology, Principal Investigator, Clinical Professor

Study Record Dates

• First Submitted: June 19, 2026
• First Posted: July 2, 2026
• Study Start: January 15, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)