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

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Pemphigus Vulgaris

Treatments: Biological: DSG3-CAART; Biological: CABA-201

Study type: Interventional

Funder types: Industry

Identifiers

NCT04422912

CAB-101

Details and patient eligibility

About

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

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

DSG3-CAART

Experimental group

Description:

Single or multiple intravenous infusion(s) of DSG3-CAART at varying dose levels. This study is now closed to enrollment.

Treatment:

Biological: DSG3-CAART

CABA-201

Experimental group

Description:

Infusion of CABA-201 with or without cyclophosphamide and fludarabine preconditioning, or with or without cyclophosphamide preconditioning. This sub-study is open to enrollment.

Treatment:

Biological: CABA-201