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 : May 6, 2023
|
Sponsor:
Cabaletta Bio
Information provided by (Responsible Party):
Cabaletta Bio
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 39 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 |
| Actual Study Start Date : | September 29, 2020 |
| Estimated Primary Completion Date : | September 2026 |
| Estimated Study Completion Date : | September 2026 |
| Arm | Intervention/treatment |
|---|---|
|
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 |
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, cyclophosphamide, and with or without fludarabine to potentially increase the in vivo expansion, persistence and activity of DSG3-CAART. |
Primary Outcome Measures :
- 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 :
- 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
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.
| 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 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
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
| Contact: Cabaletta Bio | +1 267 759 3100 | clinicaltrials@cabalettabio.com |
Locations
| United States, California | |
| Stanford University, Dept. of Dermatology | Recruiting |
| Redwood City, California, United States, 94063 | |
| Contact: Isin Sinem Bagci, MD 650-724-8829 isbagci@stanford.edu | |
| Contact: Kunju Sridhar, PhD 650 721 4902 kunju@stanford.edu | |
| Principal Investigator: M. Peter Marinkovich, MD | |
| UC Davis, Dept. of Dermatology | Recruiting |
| Sacramento, California, United States, 95816 | |
| Contact: Lauren Downing 916-551-2635 ladowning@ucdavis.edu | |
| Principal Investigator: Mehrdad Abedi, MD | |
| United States, Illinois | |
| Northwestern University | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: NU Dermatology CTU 312-503-5944 NUderm-research@northwestern.edu | |
| Principal Investigator: Alan Zhou, MD | |
| United States, Iowa | |
| University of Iowa | Recruiting |
| Iowa City, Iowa, United States, 52242 | |
| Contact: Amanda Steahr 319-384-6843 amanda-steahr@uiowa.edu | |
| Principal Investigator: Janet Fairley, MD | |
| United States, New York | |
| Mount Sinai - Icahn School of Medicine | Recruiting |
| New York, New York, United States, 10029 | |
| Contact: Jonathan Lagdameo 212-241-8552 jonathan.lagdameo@mssm.edu | |
| Contact: Giselle Singer 212-241-3288 giselle.singer@mssm.edu | |
| Principal Investigator: Keren Osman, MD | |
| United States, North Carolina | |
| University of North Carolina, Department of Dermatology | Recruiting |
| Chapel Hill, North Carolina, United States, 27516 | |
| Contact: Suzy Caballero 984-974-3682 nieves_caballero@med.unc.edu | |
| Principal Investigator: Donna A Culton, MD, PhD | |
| United States, Pennsylvania | |
| University of Pennsylvania | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Contact: Joshua Bryer, BA, CCRC 267-251-6819 jbryer@pennmedicine.upenn.edu | |
| Principal Investigator: David Porter, MD | |
| United States, Texas | |
| UT Southwestern Medical Center, Dept. of Dermatology | Recruiting |
| Dallas, Texas, United States, 75235 | |
| Contact: Aleuna Lee 214-645-8968 aleuna.lee@utsouthwestern.edu | |
| Principal Investigator: Arturo Dominguez, MD | |
| MD Anderson Texas Medical Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Dermatology Department | |
| Principal Investigator: Omar Pacha, MD | |
| United States, Washington | |
| University of Washington | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Contact: Susan Ra 206-667-5310 sra@fredhutch.org | |
| Principal Investigator: Michi Shinohara, MD | |
Sponsors and Collaborators
Cabaletta Bio
Investigators
| Study Chair: | Cabaletta Bio | Cabaletta Bio |
| 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: | May 6, 2023 |
| Last Verified: | May 2023 |
| 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:
|
Pemphigus Skin Diseases, Vesiculobullous Skin Diseases Autoimmune Diseases Immune System Diseases |