Clinical trial NCT04422912: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pemphigus Vulgaris
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
Lead sponsor: Cabaletta Bio
Sponsor class: INDUSTRY
First posted: 2020-06-09
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events, including Dose Limit Toxicity
timeFrame: 3 months
measure: For CABA-201 Sub-study: To evaluate adverse events reported by subjects
timeFrame: Up to 28 days after CABA-201 infusion
Secondary outcomes:
measure: Percent of CAAR-transduced cells
timeFrame: Baseline
measure: Total DSG3-CAART positive cells
timeFrame: Baseline
measure: Cellular kinetics profile of DSG3-CAART
timeFrame: Up to 36 months
measure: Change in DSG3 autoantibody titer
timeFrame: Up to 36 months
measure: Serologic remission
timeFrame: Up to 36 months
measure: Pemphigus Disease Area Index (PDAI)
timeFrame: Up to 36 months
measure: Clinical remission: complete remission off therapy and complete remission on minimal therapy
timeFrame: Up to 36 months
measure: Time to clinical remission and time to serologic remission
timeFrame: up to 36 months
measure: Duration of clinical remission and duration of serologic remission
timeFrame: up to 36 months
measure: For CABA-201 Sub-study: To evaluate adverse events reported by subjects
timeFrame: Up to 156 weeks after CABA-201 infusion
measure: For CABA-201 Sub-study: To characterize the pharmacodynamics (PD)
timeFrame: Up to 156 weeks
measure: For CABA-201 Sub-study: To characterize the pharmacokinetics (PK)
timeFrame: Up to 156 weeks
measure: For CABA-201 Sub-study: To evaluate autoantibody -related biomarkers
timeFrame: Up to 156 Weeks
measure: For CABA-201 Sub-study: To evaluate efficacy
timeFrame: Up to 156 Weeks
Other outcomes:
Locations:
city: Redwood City
country: United States
facility: Stanford University, Dept. of Dermatology
state: California
city: Sacramento
country: United States
facility: UC Davis, Dept. of Dermatology
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai - Icahn School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina, Department of Dermatology
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center, Dept. of Dermatology
state: Texas
city: Houston
country: United States
facility: MD Anderson Texas Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Cabaletta Bio
name: Cabaletta Bio
role: STUDY_CHAIR
References: