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)

Phase 1

Recruiting

• Conditions: Pemphigus Vulgaris
• Interventions: Biological: DSG3-CAART or CABA-201

• Registration Number: NCT04422912
• Lead Sponsor: Cabaletta Bio

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.

Study Timeline

• Study First Submitted: 2020-06-02
• Study First Submitted QC: 2020-06-05
• Study First Posted: 2020-06-09
• Study Start: 2020-09-29
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-06
• Last Update Posted: 2025-01-07
• Primary Completion: 2029-01
• Study Completion: 2029-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 55

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DSG3-CAART or CABA-201	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 characterize the pharmacokinetics (PK)	Up to 156 weeks	Levels of CABA-201-positive T cells in the blood
Total DSG3-CAART positive cells	Baseline	Total DSG3-CAART positive cells for each manufacturing run by flow cytometry
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
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
Change in DSG3 autoantibody titer	Up to 36 months	Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit
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
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)
Percent of CAAR-transduced cells	Baseline	Percent of total cells for infusion that are CAAR-transduced cells 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
Serologic remission	Up to 36 months	Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer
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

Trial Locations

Locations (10)

Stanford University, Dept. of Dermatology; 🇺🇸 Redwood City, California, United States

UC Davis, Dept. of Dermatology; 🇺🇸 Sacramento, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Mount Sinai - Icahn School of Medicine; 🇺🇸 New York, New York, United States

University of North Carolina, Department of Dermatology; 🇺🇸 Chapel Hill, North Carolina, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

UT Southwestern Medical Center, Dept. of Dermatology; 🇺🇸 Dallas, Texas, United States

MD Anderson Texas Medical Center; 🇺🇸 Houston, Texas, United States

University of Washington; 🇺🇸 Seattle, Washington, United States