Title
Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV)
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
Phase
Phase 1Lead Sponsor
Cabaletta BioStudy Type
InterventionalStatus
RecruitingIndication/Condition
Mucosal -Dominant Pemphigus VulgarisIntervention/Treatment
DSG3-CAARTStudy Participants
39Mucosal-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.
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.
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
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
