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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04422912
Recruitment Status : Recruiting
First Posted : June 9, 2020
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Cabaletta Bio

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.

Condition or disease Intervention/treatment Phase
Mucosal -Dominant Pemphigus Vulgaris Biological: DSG3-CAART Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : August 2026
Estimated Study Completion Date : August 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pemphigus

Arm Intervention/treatment
Experimental: DSG3-CAART

Cohort A: Fractionated infusions of DSG3-CAART at increasing dose levels (4 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 (2 groups) 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

Biological: DSG3-CAART
Intravenous infusions of DSG3-CAART at different doses and different fractionations




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Percent of CAAR-transduced cells [ Time Frame: Baseline ]
    Percent of total cells for infusion that are CAAR-transduced cells by flow cytometry

  2. Total DSG3-CAART positive cells [ Time Frame: Baseline ]
    Total DSG3-CAART positive cells for each manufacturing run by flow cytometry

  3. Cellular kinetics profile of DSG3-CAART [ Time Frame: Up to 36 months ]
    Cellular kinetics profile of DSG3-CAART assessed by quantitative polymerase chain reaction

  4. Change in DSG3 autoantibody titer [ Time Frame: Up to 36 months ]
    Change in DSG3 autoantibody titer by ELISA compared to pre-infusion visit

  5. Serologic remission [ Time Frame: Up to 36 months ]
    Proportion of subjects achieving serologic remission, determined by negative DSG3 ELISA titer

  6. 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

  7. 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

  8. 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

  9. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of mPV by prior biopsy and prior positive DSG3 ELISA
  • mPV inadequately managed by at least two standard immunosuppressive therapies
  • Active mPV at screening
  • DSG3 ELISA positive at screening

Exclusion Criteria:

  • Cutaneous lesions associated with PV
  • Rituximab in last 6 months
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04422912


Contacts
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Contact: Study Recruitment Center 800-711-4906 cabalettatrials@iqvia.com

Locations
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United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David Porter, MD         
Principal Investigator: David Porter, MD         
Sponsors and Collaborators
Cabaletta Bio
Investigators
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Study Chair: Cabaletta Bio Cabaletta Bio
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Responsible Party: Cabaletta Bio
ClinicalTrials.gov Identifier: NCT04422912    
Other Study ID Numbers: CAB-101
First Posted: June 9, 2020    Key Record Dates
Last Update Posted: July 1, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cabaletta Bio:
Pemphigus
Pemphigus Vulgaris
CAAR-T Therapy
CAR-T Therapy
Desmoglein 3
Cell Therapy
Autoimmune Disease
Autoimmunity
Skin Diseases, Vesiculobullous
Immunotherapy, Adoptive
Immune System Diseases
Additional relevant MeSH terms:
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Pemphigus
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases