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)
Purpose
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
Condition
- Pemphigus Vulgaris
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 Inclusion Criteria for CABA-201 sub-study - 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) - 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 - Investigational treatment in last 3 months
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental DSG3-CAART or CABA-201 |
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. OR CABA-201 Cohort: Single infusion of CABA-201. |
|
Recruiting Locations
Boston, Massachusetts 02115
More Details
- Status
- Recruiting
- Sponsor
- Cabaletta Bio
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 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. A sub-study will be conducted to investigate if CABA-201 can be safely administered while achieving clinical responses without the need for preconditioning in PV patients. DSG3-CAART or CABA-201 may potentially lead to complete and durable remission of disease.