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)

Phase 2RecruitingNCT04422912

Cabaletta Bio40 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pemphigus Vulgaris

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (13)

Stanford University, Dept. of Dermatology

Redwood City, California, United States

RECRUITING

UC Davis, Dept. of Dermatology

Sacramento, California, United States

RECRUITING

Yale University

New Haven, Connecticut, United States

RECRUITING

Northwestern University

Chicago, Illinois, United States

RECRUITING

University of Iowa

Iowa City, Iowa, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

RECRUITING

Mount Sinai - Icahn School of Medicine

New York, New York, United States

WITHDRAWN

Columbia University

New York, New York, United States

RECRUITING

University of North Carolina, Department of Dermatology

Chapel Hill, North Carolina, United States

WITHDRAWN

University of Pennsylvania

Philadelphia, Pennsylvania, United States

RECRUITING

...and 3 more locations

Outcomes

Primary Outcomes

Adverse events, including Dose Limit Toxicity

Incidence of adverse events that are related to DSG3-CAART therapy

Time frame: 3 months

For CABA-201 Sub-study: To evaluate adverse events reported by subjects

Incidence and severity of AEs

Time frame: Up to 28 days after CABA-201 infusion

Secondary Outcomes

Percent of CAAR-transduced cells

Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry

Time frame: Baseline

Total DSG3-CAART positive cells

Total DSG3-CAART positive cells for each manufacturing run by flow cytometry

Time frame: Baseline

Cellular kinetics profile of DSG3-CAART

Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction

Time frame: Up to 36 months

Change in DSG3 autoantibody titer

Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit

Time frame: Up to 36 months

Serologic remission

Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer

Time frame: Up to 36 months

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

Time frame: Up to 36 months

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 frame: Up to 36 months

Time to clinical remission and time to serologic remission

Time to clinical remission and time to serologic remission from the last infusion

Time frame: up to 36 months

Duration of clinical remission and duration of serologic remission

Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission

Time frame: up to 36 months

For CABA-201 Sub-study: To evaluate adverse events reported by subjects

Incidence and severity of AEs

Time frame: Up to 156 weeks after CABA-201 infusion

For CABA-201 Sub-study: To characterize the pharmacodynamics (PD)

Levels of B cells in the blood

Time frame: Up to 156 weeks

For CABA-201 Sub-study: To characterize the pharmacokinetics (PK)

Levels of CABA-201-positive T cells in the blood

Time frame: Up to 156 weeks

For CABA-201 Sub-study: To evaluate autoantibody -related biomarkers

Levels of serum anti-DSG3 and anti-DSG1 antibodies

Time frame: Up to 156 Weeks

For CABA-201 Sub-study: To evaluate efficacy

Absolute and percent change in disease activity by Pemphigus Disease Area Index (PDAI)

Time frame: Up to 156 Weeks

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)

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts