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

Primary Purpose

Mucosal -Dominant Pemphigus Vulgaris

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DSG3-CAART
Sponsored by
Cabaletta Bio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mucosal -Dominant Pemphigus Vulgaris focused on measuring Pemphigus, Pemphigus Vulgaris, CAAR-T Therapy, CAR-T Therapy, Desmoglein 3, Cell Therapy, Autoimmune Disease, Autoimmunity, Skin Diseases, Vesiculobullous, Immunotherapy, Adoptive, Immune System Diseases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford University, Dept. of DermatologyRecruiting
  • UC Davis, Dept. of DermatologyRecruiting
  • Northwestern UniversityRecruiting
  • University of IowaRecruiting
  • Mount Sinai - Icahn School of MedicineRecruiting
  • University of North Carolina, Department of DermatologyRecruiting
  • University of PennsylvaniaRecruiting
  • UT Southwestern Medical Center, Dept. of DermatologyRecruiting
  • MD Anderson Texas Medical CenterRecruiting
  • University of WashingtonRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DSG3-CAART

Arm Description

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

Outcomes

Primary Outcome Measures

Adverse events, including Dose Limit Toxicity
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

Percent of CAAR-transduced cells
Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry
Total DSG3-CAART positive cells
Total DSG3-CAART positive cells for each manufacturing run by flow cytometry
Cellular kinetics profile of DSG3-CAART
Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction
Change in DSG3 autoantibody titer
Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit
Serologic remission
Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer
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
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
Time to clinical remission and time to serologic remission
Time to clinical remission and time to serologic remission from the last infusion
Duration of clinical remission and duration of serologic remission
Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission

Full Information

First Posted
June 2, 2020
Last Updated
May 4, 2023
Sponsor
Cabaletta Bio
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1. Study Identification

Unique Protocol Identification Number
NCT04422912
Brief Title
Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV)
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 29, 2020 (Actual)
Primary Completion Date
September 2026 (Anticipated)
Study Completion Date
September 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cabaletta Bio

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucosal -Dominant Pemphigus Vulgaris
Keywords
Pemphigus, Pemphigus Vulgaris, CAAR-T Therapy, CAR-T Therapy, Desmoglein 3, Cell Therapy, Autoimmune Disease, Autoimmunity, Skin Diseases, Vesiculobullous, Immunotherapy, Adoptive, Immune System Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DSG3-CAART
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
DSG3-CAART
Intervention Description
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 Measure Information:
Title
Adverse events, including Dose Limit Toxicity
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Percent of CAAR-transduced cells
Description
Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry
Time Frame
Baseline
Title
Total DSG3-CAART positive cells
Description
Total DSG3-CAART positive cells for each manufacturing run by flow cytometry
Time Frame
Baseline
Title
Cellular kinetics profile of DSG3-CAART
Description
Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction
Time Frame
Up to 36 months
Title
Change in DSG3 autoantibody titer
Description
Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit
Time Frame
Up to 36 months
Title
Serologic remission
Description
Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer
Time Frame
Up to 36 months
Title
Pemphigus Disease Area Index (PDAI)
Description
Change in PDAI compared to pre-infusion visit, scored on a 0-250 scale where a greater number represents more disease activity
Time Frame
Up to 36 months
Title
Clinical remission: complete remission off therapy and complete remission on minimal therapy
Description
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
Time Frame
Up to 36 months
Title
Time to clinical remission and time to serologic remission
Description
Time to clinical remission and time to serologic remission from the last infusion
Time Frame
up to 36 months
Title
Duration of clinical remission and duration of serologic remission
Description
Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission
Time Frame
up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cabaletta Bio
Phone
+1 267 759 3100
Email
clinicaltrials@cabalettabio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cabaletta Bio
Organizational Affiliation
Cabaletta Bio
Official's Role
Study Chair
Facility Information:
Facility Name
Stanford University, Dept. of Dermatology
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isin Sinem Bagci, MD
Phone
650-724-8829
Email
isbagci@stanford.edu
First Name & Middle Initial & Last Name & Degree
Kunju Sridhar, PhD
Phone
650 721 4902
Email
kunju@stanford.edu
First Name & Middle Initial & Last Name & Degree
M. Peter Marinkovich, MD
Facility Name
UC Davis, Dept. of Dermatology
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren Downing
Phone
916-551-2635
Email
ladowning@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
Mehrdad Abedi, MD
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
NU Dermatology CTU
Phone
312-503-5944
Email
NUderm-research@northwestern.edu
First Name & Middle Initial & Last Name & Degree
Alan Zhou, MD
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Steahr
Phone
319-384-6843
Email
amanda-steahr@uiowa.edu
First Name & Middle Initial & Last Name & Degree
Janet Fairley, MD
Facility Name
Mount Sinai - Icahn School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan Lagdameo
Phone
212-241-8552
Email
jonathan.lagdameo@mssm.edu
First Name & Middle Initial & Last Name & Degree
Giselle Singer
Phone
212-241-3288
Email
giselle.singer@mssm.edu
First Name & Middle Initial & Last Name & Degree
Keren Osman, MD
Facility Name
University of North Carolina, Department of Dermatology
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27516
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suzy Caballero
Phone
984-974-3682
Email
nieves_caballero@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Donna A Culton, MD, PhD
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Bryer, BA, CCRC
Phone
267-251-6819
Email
jbryer@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
David Porter, MD
Facility Name
UT Southwestern Medical Center, Dept. of Dermatology
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aleuna Lee
Phone
214-645-8968
Email
aleuna.lee@utsouthwestern.edu
First Name & Middle Initial & Last Name & Degree
Arturo Dominguez, MD
Facility Name
MD Anderson Texas Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dermatology Department
First Name & Middle Initial & Last Name & Degree
Omar Pacha, MD
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Ra
Phone
206-667-5310
Email
sra@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Michi Shinohara, MD

12. IPD Sharing Statement

Learn more about this trial

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

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