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

May 4, 2023 updated by: Cabaletta Bio

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

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.

Study Overview

Status

Recruiting

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

39

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Redwood City, California, United States, 94063
        • Recruiting
        • Stanford University, Dept. of Dermatology
        • Contact:
        • Contact:
        • Principal Investigator:
          • M. Peter Marinkovich, MD
      • Sacramento, California, United States, 95816
        • Recruiting
        • UC Davis, Dept. of Dermatology
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Contact:
        • Principal Investigator:
          • Janet Fairley, MD
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Mount Sinai - Icahn School of Medicine
        • Contact:
        • Principal Investigator:
          • Keren Osman, MD
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27516
        • Recruiting
        • University of North Carolina, Department of Dermatology
        • Contact:
        • Principal Investigator:
          • Donna A Culton, MD, PhD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
        • Contact:
        • Principal Investigator:
          • David Porter, MD
    • Texas
      • Dallas, Texas, United States, 75235
        • Recruiting
        • UT Southwestern Medical Center, Dept. of Dermatology
        • Contact:
        • Principal Investigator:
          • Arturo Dominguez, MD
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Texas Medical Center
        • Contact:
          • Dermatology Department
        • Principal Investigator:
          • Omar Pacha, MD
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • University of Washington
        • Contact:
        • Principal Investigator:
          • Michi Shinohara, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of CAAR-transduced cells
Time Frame: Baseline
Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry
Baseline
Total DSG3-CAART positive cells
Time Frame: Baseline
Total DSG3-CAART positive cells for each manufacturing run by flow cytometry
Baseline
Cellular kinetics profile of DSG3-CAART
Time Frame: Up to 36 months
Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction
Up to 36 months
Change in DSG3 autoantibody titer
Time Frame: Up to 36 months
Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit
Up to 36 months
Serologic remission
Time Frame: Up to 36 months
Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer
Up to 36 months
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
Up to 36 months
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
Up to 36 months
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
up to 36 months
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
up to 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Chair: Cabaletta Bio, Cabaletta Bio

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 29, 2020

Primary Completion (Anticipated)

September 1, 2026

Study Completion (Anticipated)

September 1, 2026

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 (Estimate)

May 5, 2023

Last Update Submitted That Met QC Criteria

May 4, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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