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NCT04422912PHASE1, PHASE2Recruiting

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)

Cabaletta Bio

Start Date

9/29/2020

Completion Date

1/1/2029

Summary

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

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

BIOLOGICAL

DSG3-CAART

BIOLOGICAL

CABA-201

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Conditions

Pemphigus Vulgaris

Locations

Stanford University, Dept. of Dermatology

Redwood City, California 94063

United States

UC Davis, Dept. of Dermatology

Sacramento, California 95816

United States

Yale University

New Haven, Connecticut 06520

United States

Northwestern University

Chicago, Illinois 60611

United States

University of Iowa

Iowa City, Iowa 52242

United States

Brigham and Women's Hospital

Boston, Massachusetts 02115

United States

Mount Sinai - Icahn School of Medicine

New York, New York 10029

United States

Columbia University

New York, New York 10032

United States

University of North Carolina, Department of Dermatology

Chapel Hill, North Carolina 27516

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

UT Southwestern Medical Center, Dept. of Dermatology

Dallas, Texas 75235

United States

MD Anderson Texas Medical Center

Houston, Texas 77030

United States

University of Washington

Seattle, Washington 98109

United States