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Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04422912
Recruitment Status : Recruiting
First Posted : June 9, 2020
Last Update Posted : May 6, 2023
Information provided by (Responsible Party):
Cabaletta Bio

Brief Summary:
Mucosal-dominant pemphigus vulgaris (mPV) is a B-cell mediated autoimmune disorder in which painful blisters are formed on the mucosal membrane, including the mouth, nose, throat, eyelids, anus, and genitals. This phase 1 study is being 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 mPV who are inadequately managed by standard therapies. DSG3-CAART may potentially lead to complete and durable remission of disease.

Condition or disease Intervention/treatment Phase
Mucosal -Dominant Pemphigus Vulgaris Biological: DSG3-CAART Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Safety and Dosing Study of Autologous Desmoglein 3 Chimeric Autoantibody Receptor T Cells (DSG3-CAART) in Subjects With Active, Anti-DSG3, Mucosal-dominant Pemphigus Vulgaris
Actual Study Start Date : September 29, 2020
Estimated Primary Completion Date : September 2026
Estimated Study Completion Date : September 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pemphigus

Arm Intervention/treatment
Experimental: DSG3-CAART

Cohort A: Fractionated infusions of DSG3-CAART at increasing dose levels (6-9 groups) administered as a single cycle.

Cohort B: Consolidation of infusion of DSG3-CAART to fewer fractionations than in Cohort A using the selected dose from Cohort A (1 group) administered as a single cycle.

Cohort C: Infusion of final selected dose and fractionation of DSG3-CAART from Cohorts A and B (1 group) administered as a single cycle

Biological: DSG3-CAART
Intravenous infusions of DSG3-CAART alone at different doses and different fractionations. Subjects may also receive varying doses of DSG3-CAART as part of a sub-study, which will employ pre-treatment with intravenous immunoglobulin, cyclophosphamide, and with or without fludarabine to potentially increase the in vivo expansion, persistence and activity of DSG3-CAART.

Primary Outcome Measures :
  1. Adverse events, including Dose Limit Toxicity [ Time Frame: 3 months ]
    The primary endpoint of the study is the incidence of adverse events that are related to DSG3-CAART therapy within 3 months of DSG3-CAART cell infusion.

Secondary Outcome Measures :
  1. Percent of CAAR-transduced cells [ Time Frame: Baseline ]
    Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry

  2. Total DSG3-CAART positive cells [ Time Frame: Baseline ]
    Total DSG3-CAART positive cells for each manufacturing run by flow cytometry

  3. Cellular kinetics profile of DSG3-CAART [ Time Frame: Up to 36 months ]
    Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction

  4. Change in DSG3 autoantibody titer [ Time Frame: Up to 36 months ]
    Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit

  5. Serologic remission [ Time Frame: Up to 36 months ]
    Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer

  6. Pemphigus Disease Area Index (PDAI) [ Time Frame: Up to 36 months ]
    Change in PDAI compared to pre-infusion visit, scored on a 0-250 scale where a greater number represents more disease activity

  7. Clinical remission: complete remission off therapy and complete remission on minimal therapy [ Time Frame: Up to 36 months ]
    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

  8. Time to clinical remission and time to serologic remission [ Time Frame: up to 36 months ]
    Time to clinical remission and time to serologic remission from the last infusion

  9. Duration of clinical remission and duration of serologic remission [ Time Frame: up to 36 months ]
    Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

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 6 months
  • Absolute lymphocyte count < 1,000/µL at screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04422912

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Contact: Cabaletta Bio +1 267 759 3100 clinicaltrials@cabalettabio.com

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United States, California
Stanford University, Dept. of Dermatology Recruiting
Redwood City, California, United States, 94063
Contact: Isin Sinem Bagci, MD    650-724-8829    isbagci@stanford.edu   
Contact: Kunju Sridhar, PhD    650 721 4902    kunju@stanford.edu   
Principal Investigator: M. Peter Marinkovich, MD         
UC Davis, Dept. of Dermatology Recruiting
Sacramento, California, United States, 95816
Contact: Lauren Downing    916-551-2635    ladowning@ucdavis.edu   
Principal Investigator: Mehrdad Abedi, MD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: NU Dermatology CTU    312-503-5944    NUderm-research@northwestern.edu   
Principal Investigator: Alan Zhou, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Amanda Steahr    319-384-6843    amanda-steahr@uiowa.edu   
Principal Investigator: Janet Fairley, MD         
United States, New York
Mount Sinai - Icahn School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Jonathan Lagdameo    212-241-8552    jonathan.lagdameo@mssm.edu   
Contact: Giselle Singer    212-241-3288    giselle.singer@mssm.edu   
Principal Investigator: Keren Osman, MD         
United States, North Carolina
University of North Carolina, Department of Dermatology Recruiting
Chapel Hill, North Carolina, United States, 27516
Contact: Suzy Caballero    984-974-3682    nieves_caballero@med.unc.edu   
Principal Investigator: Donna A Culton, MD, PhD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Joshua Bryer, BA, CCRC    267-251-6819    jbryer@pennmedicine.upenn.edu   
Principal Investigator: David Porter, MD         
United States, Texas
UT Southwestern Medical Center, Dept. of Dermatology Recruiting
Dallas, Texas, United States, 75235
Contact: Aleuna Lee    214-645-8968    aleuna.lee@utsouthwestern.edu   
Principal Investigator: Arturo Dominguez, MD         
MD Anderson Texas Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Dermatology Department         
Principal Investigator: Omar Pacha, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Susan Ra    206-667-5310    sra@fredhutch.org   
Principal Investigator: Michi Shinohara, MD         
Sponsors and Collaborators
Cabaletta Bio
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Study Chair: Cabaletta Bio Cabaletta Bio
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Responsible Party: Cabaletta Bio
ClinicalTrials.gov Identifier: NCT04422912    
Other Study ID Numbers: CAB-101
First Posted: June 9, 2020    Key Record Dates
Last Update Posted: May 6, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cabaletta Bio:
Pemphigus Vulgaris
CAAR-T Therapy
CAR-T Therapy
Desmoglein 3
Cell Therapy
Autoimmune Disease
Skin Diseases, Vesiculobullous
Immunotherapy, Adoptive
Immune System Diseases
Additional relevant MeSH terms:
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Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases