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)

Pemphigus Vulgaris Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04422912
• Other study ID #: CAB-101
• Status: Recruiting
• Phase: Phase 1
• Start date: September 29, 2020
• Est. completion date: January 2029

Study information

• Verified date: May 2024
• Source: Cabaletta Bio
• Contact: Cabaletta Bio
• Phone: +1 267 759 3100
• Email: clinicaltrials[@]cabalettabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: January 2029
• Est. primary completion date: January 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pemphigus
• Pemphigus Vulgaris

Intervention

Biological:
• DSG3-CAART or CABA-201
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. OR CABA-201: Single intravenous infusion of CABA-201.

Locations

Country	Name	City	State
United States	University of North Carolina, Department of Dermatology	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	UT Southwestern Medical Center, Dept. of Dermatology	Dallas	Texas
United States	MD Anderson Texas Medical Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Mount Sinai - Icahn School of Medicine	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Stanford University, Dept. of Dermatology	Redwood City	California
United States	UC Davis, Dept. of Dermatology	Sacramento	California
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Cabaletta Bio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events, including Dose Limit Toxicity	Incidence of adverse events that are related to DSG3-CAART therapy	3 months
Primary	For CABA-201 Sub-study: To evaluate adverse events reported by subjects	Incidence and severity of AEs	Up to 28 days after CABA-201 infusion
Secondary	Percent of CAAR-transduced cells	Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry	Baseline
Secondary	Total DSG3-CAART positive cells	Total DSG3-CAART positive cells for each manufacturing run by flow cytometry	Baseline
Secondary	Cellular kinetics profile of DSG3-CAART	Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction	Up to 36 months
Secondary	Change in DSG3 autoantibody titer	Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit	Up to 36 months
Secondary	Serologic remission	Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer	Up to 36 months
Secondary	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	Up to 36 months
Secondary	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	Up to 36 months
Secondary	Time to clinical remission and time to serologic remission	Time to clinical remission and time to serologic remission from the last infusion	up to 36 months
Secondary	Duration of clinical remission and duration of serologic remission	Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission	up to 36 months
Secondary	For CABA-201 Sub-study: To evaluate adverse events reported by subjects	Incidence and severity of AEs	Up to 156 weeks after CABA-201 infusion
Secondary	For CABA-201 Sub-study: To characterize the pharmacodynamics (PD)	Levels of B cells in the blood	Up to 156 weeks
Secondary	For CABA-201 Sub-study: To characterize the pharmacokinetics (PK)	Levels of CABA-201-positive T cells in the blood	Up to 156 weeks
Secondary	For CABA-201 Sub-study: To evaluate autoantibody -related biomarkers	Levels of serum anti-DSG3 and anti-DSG1 antibodies	Up to 156 Weeks
Secondary	For CABA-201 Sub-study: To evaluate efficacy	Absolute and percent change in disease activity by Pemphigus Disease Area Index (PDAI)	Up to 156 Weeks