Polyclonal Regulatory T Cells (PolyTregs) for Pemphigus

NCT03239470 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: DAIT APG01APG01NIAID CRMS ID#: 37534
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

T cells, a type of white blood cell called a lymphocyte, play an important role in the immune system. One subtype, the regulatory T cell (Treg) helps to regulate the immune system and may provide protection against the development of autoimmune disease. The hope is that these naturally occurring Treg cells can be utilized for the treatment of autoimmune disease and potentially replace the use of chronic immunosuppressive therapies that are associated with multiple side effects. There has been a small study showing safe administration of Tregs with decreased disease activity in patients with insulin-dependent diabetes. Tregs are being studied in lupus, cancer and organ transplantation. This phase I trial will be conducted as an open-label, dose-escalation, multicenter trial in adult participants with active pemphigus.The purpose of this study is to test the safety and effect of Treg therapy in participants who have skin (cutaneous) involvement due to pemphigus.

Conditions

Pemphigus Foliaceus; Pemphigus Vulgaris

Keywords

autologous polyclonal regulatory T cell therapy; PolyTregs; open-label; Phase 1 (safety)

Outcome Measures

Primary Outcomes (1)

• Number of Significant Adverse Events Through Week 52

  Number of significant adverse events, defined as any related National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 Grade 3 or higher adverse event or any related serious adverse event (SAE). Related is defined as being possibly related or related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee. An SAE is any untoward medical occurrence that, at any dose\* results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. \*Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.

  Up to Week 52

Secondary Outcomes (12)

• Number of Significant Adverse Events

  From the start of investigational product infusion through Week 156.

• Number of All Adverse Events

  From the start of investigational product infusion through Week 156.

• Number of All NCI-CTCAE Grade 3 or Higher Adverse Events

  From the start of investigational product infusion through Week 52.

• Number of All NCI-CTCAE Grade 3 or Higher Adverse Events

  From the start of investigational product infusion through Week 156.

• Number of All SAEs

  From the start of investigational product infusion through Week 156.

Study Arms (2)

Cohort 1: 1.0 x 10^8 PolyTregs

EXPERIMENTAL

A single intravenous infusion of 1.0 x 10\^8 PolyTregs will be administered.

Biological: Cohort 1: 1.0 x 10^8 PolyTregs

Cohort 2: 2.5x10^8 PolyTregs

EXPERIMENTAL

A single intravenous infusion of 2.5x10\^8 PolyTregs will be administered.

Biological: Cohort 2: 2.5x10^8 PolyTregs

Interventions

Cohort 1: 1.0 x 10^8 PolyTregs BIOLOGICAL

Each participant will receive a target cell dose of 1.0 x 10\^8 polyclonal Tregs.

Also known as: Polyclonal Regulatory T Cells, autologous PolyTregs, CD4+CD127lo/negCD25+ PolyTregs

Cohort 1: 1.0 x 10^8 PolyTregs

Cohort 2: 2.5x10^8 PolyTregs BIOLOGICAL

Each participant will receive a target cell dose of 2.5x10\^8 polyclonal Tregs.

Also known as: Polyclonal Regulatory T Cells, autologous PolyTregs, CD4+CD127lo/negCD25+ PolyTregs

Cohort 2: 2.5x10^8 PolyTregs

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent;
• Diagnosis of Pemphigus Vulgaris (PV) or Pemphigus Foliaceus (PF), defined by H\&E staining (e.g., Haemotoxylin and Eosin) and direct immunofluorescence staining of skin biopsy at any time prior to enrollment;
• Pemphigus treated with systemic corticosteroids within the 2 years prior to screening (historic or current), or treated with rituximab ≥ 12 months prior to screening;
• Presence of:
• anti-Dsg3 antibodies (\>20.0 U/ml) at screening visit consistent with diagnosis of pemphigus vulgaris or,
• anti-Dsg1 antibodies (\>20.0 U/ml) at screening visit consistent with diagnosis of pemphigus foliaceus.
• Active of PV or PF as defined by Pemphigus Disease Area Index (PDAI) overall activity score 3-10 at screening visit, and PDAI overall activity score 1-12 at baseline visit;
• Positive test for Epstein-Barr Virus (EBV) antibody;
• Adequate venous access to support draw of 400 ml whole blood and infusion of investigational therapy; and
• An absolute Treg count of ≥ 42 cells/μL within 6 weeks prior to whole blood collection at Week -2 (i.e., 2 weeks prior to planned PolyTreg Infusion).

You may not qualify if:

• Initiation of systemic corticosteroid therapy, prednisone dose \> 25 mg/d (or equivalent) or change in prednisone dose within 4 weeks prior to screening;
• Addition of a new medication, or change in the dose of any background medication used to treat any aspect of pemphigus within the timeframes listed below. Specifically:
• methotrexate, mycophenolate mofetil, mycophenolic acid, azathioprine, cyclosporine or dapsone within the 6 weeks prior to screening or in the time between screening and study drug infusion,
• intravenous Immunoglobulin (IVIG) within 12 weeks prior to screening or in the time between screening and study drug infusion (subjects on IVIG must be on stable dose for at least 12 weeks prior to screening),
• treatment with cyclophosphamide within 12 weeks prior to screening or in the time between screening and study drug infusion.
• Doses of background medications at screening:
• methotrexate \> 25 mg/week,
• mycophenolate mofetil \> 3000 mg/d,
• mycophenolic acid \> 1080 mg/bid,
• azathioprine \> 200 mg/d,
• cyclosporine \> 2 mg/kg/d,
• dapsone \>250 mg/d,or
• intravenous immunoglobulin (IVIG) \> 4mg/kg monthly.
• Use of rituximab within the 12 months prior to screening;
• Change in dosing frequency, concentration, or applied surface area of topical steroids and/or topical calcineurin inhibitors within 2 weeks prior to screening;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (4)

University of California San Francisco School of Medicine: Department of Dermatology

San Francisco, California, 94115, United States

Location

University of Iowa Health Care: Department of Dermatology

Iowa City, Iowa, 52242, United States

Location

Duke University Medical Center: Department of Dermatology

Durham, North Carolina, 27710, United States

Location

University of Texas Southwestern Medical Center: Department of Dermatology

Dallas, Texas, 75390, United States

Location

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website
• Autoimmunity Centers of Excellence (ACE) website

MeSH Terms

Conditions

Pemphigus

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Enrollment was stopped early, on May 1, 2020, due to: * Lack of recruitment, * Ongoing and new feasibility issues, including the recent approval of rituximab for treatment of pemphigus, and * The impact of the coronavirus infectious disease 19 (COVID-19) pandemic. No participants were enrolled in Cohort 2.

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

240-669-5064

Study Officials

• Haley Naik, MD,MHSc

  University of California San Francisco School of Medicine: Department of Dermatology

  STUDY CHAIR

• Anna Haemel, MD

  University of California San Francisco School of Medicine: Department of Dermatology

  STUDY CHAIR

• Michael Rosenblum, MD, Ph.D.

  University of California San Francisco School of Medicine: Department of Dermatology

  STUDY CHAIR

• Jeffrey Bluestone, Ph.D.

  UCSF School of Medicine: UCSF Diabetes Clinic

  STUDY CHAIR

• David Wofsy, M.D.

  University of California San Francisco School of Medicine: Lupus Clinic and Rheumatology Clinical Research Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 4, 2017
• Study Start: October 10, 2017
• Primary Completion: December 10, 2020
• Study Completion: January 9, 2023
• Last Updated: February 15, 2024
• Results First Posted: November 22, 2021

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (4)