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Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV)

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ClinicalTrials.gov Identifier: NCT04422912
Recruitment Status : Recruiting
First Posted : June 9, 2020
Last Update Posted : December 2, 2022
Sponsor:
Information provided by (Responsible Party):
Cabaletta Bio

Tracking Information
First Submitted Date  ICMJE June 2, 2020
First Posted Date  ICMJE June 9, 2020
Last Update Posted Date December 2, 2022
Actual Study Start Date  ICMJE September 29, 2020
Estimated Primary Completion Date September 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2020)
Adverse events, including Dose Limit Toxicity [ Time Frame: 3 months ]
The primary endpoint of the study is the incidence of adverse events that are related to DSG3-CAART therapy within 3 months of DSG3-CAART cell infusion.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2020)
  • Percent of CAAR-transduced cells [ Time Frame: Baseline ]
    Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry
  • Total DSG3-CAART positive cells [ Time Frame: Baseline ]
    Total DSG3-CAART positive cells for each manufacturing run by flow cytometry
  • Cellular kinetics profile of DSG3-CAART [ Time Frame: Up to 36 months ]
    Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction
  • Change in DSG3 autoantibody titer [ Time Frame: Up to 36 months ]
    Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit
  • Serologic remission [ Time Frame: Up to 36 months ]
    Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer
  • Pemphigus Disease Area Index (PDAI) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to 36 months ]
    Duration of clinical remission and duration of serologic remission sustained after achieving the initial remission
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open-label Study to Determine the Maximum Tolerated Dose of DSG3-CAART in Mucosal-dominant PV Patients (mPV)
Official Title  ICMJE A Phase 1, Open-label, Safety and Dosing Study of Autologous Desmoglein 3 Chimeric Autoantibody Receptor T Cells (DSG3-CAART) in Subjects With Active, Anti-DSG3, Mucosal-dominant Pemphigus Vulgaris
Brief Summary Mucosal-dominant pemphigus vulgaris (mPV) is a B-cell mediated autoimmune disorder in which painful blisters are formed on the mucosal membrane, including the mouth, nose, throat, eyelids, anus, and genitals. This phase 1 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 mPV who are inadequately managed by standard therapies. DSG3-CAART may potentially lead to complete and durable remission of disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mucosal -Dominant Pemphigus Vulgaris
Intervention  ICMJE Biological: DSG3-CAART
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 and cyclophosphamide to potentially increase the in vivo expansion, persistence and activity of DSG3-CAART.
Study Arms  ICMJE Experimental: DSG3-CAART

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

Intervention: Biological: DSG3-CAART
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2022)
39
Original Estimated Enrollment  ICMJE
 (submitted: June 5, 2020)
30
Estimated Study Completion Date  ICMJE September 2026
Estimated Primary Completion Date September 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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 6 months
  • Absolute lymphocyte count < 1,000/µL at screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cabaletta Bio +1 267 759 3100 clinicaltrials@cabalettabio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04422912
Other Study ID Numbers  ICMJE CAB-101
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Cabaletta Bio
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Cabaletta Bio
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Cabaletta Bio Cabaletta Bio
PRS Account Cabaletta Bio
Verification Date November 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP