Pemphigus Vulgaris
Conditions
Keywords
Pemphigus, Pemphigus Vulgaris, CAAR-T Therapy, CAR-T Therapy, Desmoglein 3, Cell Therapy, Autoimmune Disease, Autoimmunity, Skin Diseases, Vesiculobullous, Immunotherapy, Adoptive, Immune System Diseases, CABA-201, Anti-CD19 CAR-T therapy, Resecabtagene Autoleucel, Rese-cel
Brief 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.
Interventions
BIOLOGICALDSG3-CAART
Intravenous infusions of DSG3-CAART alone at different doses and different fractionations, with or without intravenous immunoglobulin, cyclophosphamide, and/or fludarabine.
BIOLOGICALCABA-201
Single intravenous infusion of CABA-201 at escalating doses, with or without preconditioning.
Sponsors
Cabaletta Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events, including Dose Limit Toxicity | 3 months | Incidence of adverse events that are related to DSG3-CAART therapy |
| For CABA-201 Sub-study: To evaluate adverse events reported by subjects | Up to 28 days after CABA-201 infusion | Incidence and severity of AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of CAAR-transduced cells | Baseline | Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry |
| Total DSG3-CAART positive cells | Baseline | Total DSG3-CAART positive cells for each manufacturing run by flow cytometry |
| Cellular kinetics profile of DSG3-CAART | Up to 36 months | Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction |
| Change in DSG3 autoantibody titer | Up to 36 months | Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit |
| Serologic remission | Up to 36 months | Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer |
| Pemphigus Disease Area Index (PDAI) | Up to 36 months | Change in PDAI compared to pre-infusion visit, scored on a 0-250 scale where a greater number represents more disease activity |
| Clinical remission: complete remission off therapy and complete remission on minimal therapy | Up to 36 months | 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 to clinical remission and time to serologic remission | up to 36 months | Time to clinical remission and time to serologic remission from the last infusion |
| Duration of clinical remission and duration of serologic remission | up to 36 months | Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission |
| For CABA-201 Sub-study: To evaluate adverse events reported by subjects | Up to 156 weeks after CABA-201 infusion | Incidence and severity of AEs |
| For CABA-201 Sub-study: To characterize the pharmacodynamics (PD) | Up to 156 weeks | Levels of B cells in the blood |
| For CABA-201 Sub-study: To characterize the pharmacokinetics (PK) | Up to 156 weeks | Levels of CABA-201-positive T cells in the blood |
| For CABA-201 Sub-study: To evaluate autoantibody -related biomarkers | Up to 156 Weeks | Levels of serum anti-DSG3 and anti-DSG1 antibodies |
| For CABA-201 Sub-study: To evaluate efficacy | Up to 156 Weeks | Absolute and percent change in disease activity by Pemphigus Disease Area Index (PDAI) |
Countries
United States
Contacts
CONTACTCabaletta Bio
STUDY_CHAIRCabaletta Bio
Cabaletta Bio
Outcome results
None listed