A Phase 1/2, Open-label, Safety and Dosing Study of Autologous CART Cells (Desmoglein 3 Chimeric Autoantibody Receptor T Cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T Cells [CABA-201]) in Subjects With Active, Pemphigus Vulgaris (RESET-PV)

A Phase 1/2, Open-label, Safety and Dosing Study of Autologous CART Cells (Desmoglein 3 Chimeric Autoantibody Receptor T Cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T Cells [CABA-201]) in Subjects With Active, Pemphigus Vulgaris

A phase 1/2, open-label, safety and dosing study of autologous CART cells (desmoglein 3 chimeric autoantibody receptor T cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T cells [CABA-201]) in subjects with active, pemphigus vulgaris

Study Overview

• Status: Recruiting
• Conditions: Pemphigus Vulgaris
• Intervention / Treatment: Biological: DSG3-CAART; Biological: CABA-201

Detailed Description

Pemphigus vulgaris (PV) is a B-cell mediated autoimmune disorder in which painful blisters are formed on the skin or mucosal membrane, including the mouth, nose, throat, eyelids, anus, and genitals.

This phase 1/2 study is being conducted in two parts. The first part is the main study conducted to find the maximum tolerated dose and optimal fractionated infusion schedule of an investigational cell therapy, DSG3-CAART, that can be given to patients with mucosal PV who are inadequately managed by standard therapies. This study is closed to enrollment.

The second part is a sub-study is being conducted to investigate if CABA-201, also called resecabtagene autoleucel, or "rese-cel", can be safely administered while achieving clinical responses without the need for preconditioning in mucosal-dominant PV (mPV) and mucocutaneous PV (mcPV) patients. This sub-study is open to enrollment.

DSG3-CAART or CABA-201 may potentially lead to complete and durable remission of disease.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Cabaletta Bio; Phone Number: 4444 +1 267 759 3100; Email: clinicaltrials@cabalettabio.com

Study Locations

• United States
  • California
    • Redwood City, California, United States, 94063
      • Recruiting
      • Stanford University, Dept. of Dermatology
      • Principal Investigator: M. Peter Marinkovich, MD
      • Contact: Kunju Sridhar, PhD; Phone Number: 650-721-4902; Email: kunju@stanford.edu
    • Sacramento, California, United States, 95816
      • Recruiting
      • UC Davis, Dept. of Dermatology
      • Contact: Lauren Downing; Phone Number: 916-551-2635; Email: ladowning@ucdavis.edu
      • Principal Investigator: Mehrdad Abedi, MD
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
      • Principal Investigator: Mary Tomayko, MD, PhD
      • Contact: Andrea DeClement; Phone Number: 475-255-8031; Email: andrea.declement@yale.edu
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: NU Dermatology CTU; Phone Number: 312-503-5944; Email: NUderm-research@northwestern.edu
      • Principal Investigator: Alan Zhou, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Amanda Howell; Phone Number: 319-384-6843; Email: amanda-steahr@uiowa.edu
      • Principal Investigator: Emma Killoran, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Principal Investigator: Arash Mostaghimi, MD, MPH, FAAD
      • Contact: Sydney Chase; Phone Number: 617-525-7638; Email: schase@bwh.harvard.edu
      • Contact: Rebecca Wenzel-Rideout; Email: rwenzel-rideout@bwh.harvard.edu
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Contact: Hei Ton "Jason" Chan; Phone Number: 646-317-6360; Email: htc2110@cumc.columbia.edu
      • Principal Investigator: Alexandra Coromilas, MD
    • New York, New York, United States, 10029
      • Withdrawn
      • Mount Sinai - Icahn School of Medicine
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • Withdrawn
      • University of North Carolina, Department of Dermatology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: David Porter, MD
      • Contact: Marie DeMarco; Phone Number: 215-349-5699; Email: marie.demarco@pennmedicine.upenn.edu
  • Texas
    • Dallas, Texas, United States, 75235
      • Recruiting
      • UT Southwestern Medical Center, Dept. of Dermatology
      • Contact: Aleuna Lee; Phone Number: 214-645-8968; Email: aleuna.lee@utsouthwestern.edu
      • Principal Investigator: Arturo Dominguez, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Texas Medical Center
      • Principal Investigator: Omar Pacha, MD
      • Contact: Alda Ashu; Phone Number: 713-792-1280; Email: abmiraso@mdanderson.org
  • Washington
    • Seattle, Washington, United States, 98109
      • Completed
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for DSG3-CAART: Closed to enrollment

• Confirmed diagnosis of mPV by prior or screening biopsy and prior positive anti- DSG3 antibody ELISA
• mPV inadequately managed by at least one standard immunosuppressive therapies
• Active mPV at screening
• Anti-DSG3 antibody ELISA positive at screening

Inclusion Criteria for CABA-201 sub-study: Open to enrollment

• Age ≥18
• Confirmed diagnosis of PV by prior or screening biopsy and prior positive DSG3 ELISA, IIF, and/or DIF
• PV inadequately managed by at least one standard immunosuppressive therapy
• Active PV at screening
• DSG3 ELISA positive at screening

Exclusion Criteria:

• Active cutaneous lesions associated with PV that indicates mucocutaneous rather than mucosal-dominant disease
• Rituximab in last 12 months unless PV symptoms have recently worsened or anti-DSG3 antibody titers have recently increased
• Prednisone > 0.25mg/kg/day
• Other autoimmune disorder requiring immunosuppressive therapies
• Investigational treatment in last 3 months

Exclusion Criteria for CABA-201 sub-study

• Have paraneoplastic pemphigus or active malignancy (not including non-melanoma skin cancer) or malignancy diagnosed within the previous 5 years
• Have received rituximab or other anti-CD20 or anti-CD19 therapies in last 12 months unless anti-DSG3 antibody titers have recently increased or PV symptoms have recently worsened
• Prednisone > 0.25mg/kg/day
• Other autoimmune disorder requiring immunosuppressive therapies
• Treatment with any investigational agent within 4 weeks or 5 half-lives, whichever is longer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DSG3-CAART; Single or multiple intravenous infusion(s) of DSG3-CAART at varying dose levels. This study is now closed to enrollment.	Biological: DSG3-CAART; Intravenous infusions of DSG3-CAART alone at different doses and different fractionations, with or without intravenous immunoglobulin, cyclophosphamide, and/or fludarabine.
Experimental: CABA-201; Infusion of CABA-201 with or without cyclophosphamide and fludarabine preconditioning, or with or without cyclophosphamide preconditioning. This sub-study is open to enrollment.	Biological: CABA-201; Single intravenous infusion of CABA-201 at escalating doses, with or without preconditioning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events, including Dose Limit Toxicity	Incidence of adverse events that are related to DSG3-CAART therapy	3 months
For CABA-201 Sub-study: To evaluate adverse events reported by subjects	Incidence and severity of AEs	Up to 28 days after CABA-201 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of CAAR-transduced cells	Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry	Baseline
Total DSG3-CAART positive cells	Total DSG3-CAART positive cells for each manufacturing run by flow cytometry	Baseline
Cellular kinetics profile of DSG3-CAART	Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction	Up to 36 months
Change in DSG3 autoantibody titer	Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit	Up to 36 months
Serologic remission	Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer	Up to 36 months
Pemphigus Disease Area Index (PDAI)	Change in PDAI compared to pre-infusion visit, scored on a 0-250 scale where a greater number represents more disease activity	Up to 36 months
Clinical remission: complete remission off therapy and complete remission on minimal therapy	Proportion of subjects achieving complete remission, determined by a PDAI activity score of 0 for at least 2 months, either off therapy or on minimal therapy	Up to 36 months
Time to clinical remission and time to serologic remission	Time to clinical remission and time to serologic remission from the last infusion	up to 36 months
Duration of clinical remission and duration of serologic remission	Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission	up to 36 months
For CABA-201 Sub-study: To evaluate adverse events reported by subjects	Incidence and severity of AEs	Up to 156 weeks after CABA-201 infusion
For CABA-201 Sub-study: To characterize the pharmacodynamics (PD)	Levels of B cells in the blood	Up to 156 weeks
For CABA-201 Sub-study: To characterize the pharmacokinetics (PK)	Levels of CABA-201-positive T cells in the blood	Up to 156 weeks
For CABA-201 Sub-study: To evaluate autoantibody -related biomarkers	Levels of serum anti-DSG3 and anti-DSG1 antibodies	Up to 156 Weeks
For CABA-201 Sub-study: To evaluate efficacy	Absolute and percent change in disease activity by Pemphigus Disease Area Index (PDAI)	Up to 156 Weeks

Collaborators and Investigators

• Sponsor: Cabaletta Bio
• Investigators: Study Chair: Cabaletta Bio, Cabaletta Bio

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: June 2, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Immune System Diseases; Autoimmunity; Immunotherapy, Adoptive; Autoimmune Disease; CAR-T Therapy; Pemphigus Vulgaris; Pemphigus; CAAR-T Therapy; Desmoglein 3; Skin Diseases, Vesiculobullous; CABA-201; Anti-CD19 CAR-T therapy; Rese-cel; Resecabtagene Autoleucel
• Additional Relevant MeSH Terms: Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Pemphigus; Immune System Diseases; Skin Diseases, Vesiculobullous
• Other Study ID Numbers: CAB-101

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