Polyclonal Regulatory T Cells (PolyTregs) for Pemphigus

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03239470
• Collaborator: Autoimmunity Centers of Excellence (Other), Rho Federal Systems Division, Inc. (Industry)
• Enrollment: 5
• Locations: 4
• Arms: 2
• Anticipated Duration (Months): 61.7
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pemphigus Foliaceus; Pemphigus Vulgaris	Biological: Cohort 1: 1.0 x 10^8 PolyTregs; Biological: Cohort 2: 2.5x10^8 PolyTregs	Phase 1

Detailed Description

Up to 12 adults between the ages of 18 and 75 years of age who have been diagnosed with pemphigus and meet all other entry criteria will be enrolled to receive one infusion of their own expanded Tregs at one of the following doses:

• 1.0 x 10^8 PolyTregs or

• 2.5 x 10^8 PolyTregs.

Safety, disease activity, and mechanism of action will be assessed over a three year period, using biospecimens from blood and skin. Study therapy administration will occur during an overnight stay, followed by 2 weekly visits, then monthly visits from Week 8 to Week 12, then quarterly visits from Week 26 to Week 52, then twice a year visits until Week 156.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Open-Label, Multicenter Trial Exploring the Safety and Tolerability of Autologous Polyclonal Regulatory T Cell Therapy in Adults With Active Pemphigus (APG01)
• Actual Study Start Date: Oct 10, 2017
• Actual Primary Completion Date: Dec 10, 2020
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: 1.0 x 10^8 PolyTregs A single intravenous infusion of 1.0 x 10^8 PolyTregs will be administered.	Biological: Cohort 1: 1.0 x 10^8 PolyTregs; Each participant will receive a target cell dose of 1.0 x 10^8 polyclonal Tregs.; Other Names: Polyclonal Regulatory T Cells autologous PolyTregs CD4+CD127lo/negCD25+ PolyTregs
Experimental: Cohort 2: 2.5x10^8 PolyTregs A single intravenous infusion of 2.5x10^8 PolyTregs will be administered.	Biological: Cohort 2: 2.5x10^8 PolyTregs; Each participant will receive a target cell dose of 2.5x10^8 polyclonal Tregs.; Other Names: Polyclonal Regulatory T Cells autologous PolyTregs CD4+CD127lo/negCD25+ PolyTregs

Outcome Measures

Primary Outcome Measures

1. Number of Significant Adverse Events Through Week 52 [Up to 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.

Secondary Outcome Measures

1. Number of Significant Events Through Week 156 [Up to Week 156]

   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. 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.

2. Number of Participants With Adverse Events (AEs) Related to Treatment, Polyclonal Tregs Infusion Through Week 52 [Up to Week 52]

   All adverse events (AEs) of specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) as a measure of safety and toxicity of the PolyTregs infusion*. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.

3. Number of Grade 3 to 5 Adverse Events (AEs) Through Week 52 [Up to Week 52]

   All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.

4. Number of Grade 3 to 5 Adverse Events (AEs) Through Week 156 [Up to Week 156]

   All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.

5. Number of Serious Adverse Events (SAEs) Through Week 156 [Up to Week 156]

   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.

6. Number of Infection-Related Adverse Events (AEs) Through Week 156 [Up to Week 156]

   Safety measure. Monitoring for signs and symptoms of infection-related AEs (e.g., viral, bacterial, or fungal organism, particularly opportunistic infections).

7. Number of Infusion-Related Reactions Within 24 Hours of PolyTregs Infusion [Up to 24 hours post infusion]

   Any infusion-related adverse events (AEs) Grade 1 or higher that occur within 24 hours of polyclonal Tregs* infusion. This study will grade the severity of AEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.

8. Change From Baseline in Pemphigus Disease Area Index (PDAI) [From Baseline (Week 0) to Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156]

   Pemphigus Disease Area Index (PDAI) is a cutaneous and mucosal disease activity assessment performed by the investigator, based on evaluation of lesions in well-defined anatomical locations. The score is weighted for the number and size of lesions, with a score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion(s), are scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranges from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.

9. Change From Baseline in Desmoglein (DSG) Autoantibody Titers [Up to Week 156]

   Desmoglein (DSG) autoantibodies serum levels, measured by ELISA (enzyme-linked immunosorbent assay, compared to pre PolyTregs infusion DSG autoantibody levels*. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.

10. Time to Initial Flare/Relapse by Week 156 [Up to Week 156]

    Time from initiation of polyTregs infusion* to the the time of the appearance of ≥3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the polyTregs infusion initiation. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.

11. Number of Participants on a Prednisone Dose ≤10 Milligrams Per Day (mg/Day) [Up to Week 156]

    A measure of efficacy. This will be assessed at Weeks 12, 26, 39, 52, 78, 104, 130, and 156.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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;

• Paraneoplastic pemphigus;

• Pemphigus erythematosus;

• Pemphigus vegetans;

• Immunoglobulin A (IgA) pemphigus;

• Drug-induced pemphigus;

• Blood donation within 10 weeks prior to baseline visit (Day 0);

• Hemoglobin < 10 g/dL;

• White blood cell (WBC) count < 3,000/ mm^{3 (equivalent to < 3 x10}9/L);

• Lymphocyte count < 800/mm^{3 (equivalent to < 0.8 x10}9/L);

• Absolute neutrophil count < 1,500/mm^{3 (equivalent to < 1.5 x10}9/L);

• Platelets < 100,000/mm^{3 (equivalent to < 100 x 10}9/L);

• Liver function test [aspartate aminotransferase (AST)], alanine aminotransferase (ALT), or alkaline phosphatase (ALK)] results that are ≥ 2 times the upper limit of normal (ULN);

• Direct bilirubin > ULN;

• End stage renal disease [estimated glomerular filtration rate (eGFR) < 20 ml/min/1.73m^2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation];

• At or within three months of screening:

• a positive QuantiFERON(R)-TB Gold test or positive purified protein derivative tuberculin skin test (PPD) [>5mm induration, regardless of Bacille Calmette Guerin (BCG) vaccine administration] unless completion of treatment has been documented for active Tuberculosis (TB),

• an indeterminate QuantiFERON (R)-TB Gold test unless followed by a subsequent negative PPD or negative QuantiFERON(R)-TB Gold test as well as a consultation with and clearance by local infectious disease (ID) department.

• Recent or ongoing active bacterial, viral, fungal, or opportunistic infections requiring systemic anti-infective therapy;

• Evidence of current or prior infection with human immunodeficiency virus (HIV), hepatitis B [as assessed by HBsAg and anti-hepatitis B core antigen (HBc) Ab] or hepatitis C [as assessed by anti-Hepatitis C Virus (anti-HCV) Ab];

• Detectable circulating EBV or Cytomegalovirus (CMV) genomes or active infection;

• Chronic infection that is currently being treated with suppressive anti-infective therapy, including but not limited to tuberculosis, pneumocystis, CMV, herpes zoster, and atypical mycobacteria, with the exception of historical orolabial or localized cutaneous herpes simplex infections treated with suppressive anti- viral therapy;

• Receipt of a live-attenuated vaccine within 12 months prior to screening;

• Concomitant malignancies or a history of malignancy, with the exception of completely treated basal cell carcinoma of the skin;

• Pregnancy;

• Lactating or breastfeeding;

• Unwilling or unable to use reliable method(s) of contraception:

• For females of child-bearing potential, from four weeks prior to Day 0 through

1 year after Treg dosing;

• For males, from the day of Treg infusion (baseline visit) to three months after Treg infusion.

• Use of an investigational therapeutic medication, or other biologic medications except rituximab, within the past 90 days, or 5 half-lives prior to screening, whichever is greater;

• Concomitant medical condition that places the subject at risk by participating in this study, including but not limited to:

• another severe, systemic autoimmune disease or condition (besides pemphigus) requiring systemic immunosuppressive therapy (e.g., rheumatoid arthritis, Systemic Lupus Erythematosus (SLE), systemic sclerosis, primary Sjogren's syndrome, primary vasculitis, psoriasis, multiple sclerosis, ankylosing spondylitis, and inflammatory bowel disease), or

• severe, progressive, or poorly controlled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease, or

• history of significant infection or recurrent infection that, in the investigator's opinion, places the subject at risk by participating in this study, or

• any other concomitant medical condition that, in the investigator's opinion, places the subject at risk by participating in this study.

• Comorbidities requiring glucocorticoid therapy, including those which have required three or more courses of systemic glucocorticoids within the previous 12 months;

• Current or history within the past year of substance abuse; or

• Inability to comply with study and follow-up procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco School of Medicine: Department of Dermatology	San Francisco	California	United States	94115
2	University of Iowa Health Care: Department of Dermatology	Iowa City	Iowa	United States	52242
3	Duke University Medical Center: Department of Dermatology	Durham	North Carolina	United States	27710
4	University of Texas Southwestern Medical Center: Department of Dermatology	Dallas	Texas	United States	75390

Sponsors and Collaborators

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

Investigators

• Study Chair: 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 Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 17, 2018

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03239470
• Other Study ID Numbers: DAIT APG01; APG01; NIAID CRMS ID#: 37534
• First Posted: Aug 4, 2017
• Last Update Posted: Nov 22, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): autologous polyclonal regulatory T cell therapy; PolyTregs; open-label; Phase 1 (safety)
• Additional relevant MeSH terms: Pemphigus

Study Results

Participant Flow

Recruitment Details	Ten participants were screened at four sites in the United States, and 5 of those participants initiated blood donation. Enrollment occurred between October 2017 and May 2020. The first participant was enrolled on October 10, 2017.

Arm/Group Title	Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose	Cohort 2: Polyclonal Treg Infusion (Poly Tregs) High Dose
Arm/Group Description	Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.	Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 2.5 x 10^8 PolyTregs. Study enrollment was closed prior to enrolling participants into Cohort 2.
Period Title: Blood Donation
STARTED	5	0
COMPLETED	5	0
NOT COMPLETED	0	0
Period Title: Blood Donation
STARTED	5	0
COMPLETED	4	0
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose
Arm/Group Description	Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.
Overall Participants	4
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.8 (14.2)
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 50%
Not Hispanic or Latino	2 50%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	4 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	4 100%
Type of Pemphigus (Count of Participants)
Pemphigus Vulgaris	3 75%
Pemphigus Foliaceus	1 25%
Age at Diagnosis of Pemphigus (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.5 (16.9)

Outcome Measures

1. Primary Outcome

Title	Number of Significant Adverse Events Through Week 52
Description	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.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.

Arm/Group Title	Cohort 1: Polyclonal Treg Infusion (PolyTregs)
Arm/Group Description	Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.
Measure Participants	4
Number [Number of Events]	0

2. Secondary Outcome

Title	Number of Significant Events Through Week 156
Description	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. 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.
Time Frame	Up to Week 156

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) Related to Treatment, Polyclonal Tregs Infusion Through Week 52
Description	All adverse events (AEs) of specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) as a measure of safety and toxicity of the PolyTregs infusion*. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Number of Grade 3 to 5 Adverse Events (AEs) Through Week 52
Description	All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Number of Grade 3 to 5 Adverse Events (AEs) Through Week 156
Description	All adverse events (AEs) within specified grades, 3 to 5, according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03), as a measure of safety and toxicity of the PolyTregs infusion*. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
Time Frame	Up to Week 156

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Number of Serious Adverse Events (SAEs) Through Week 156
Description	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.
Time Frame	Up to Week 156

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Number of Infection-Related Adverse Events (AEs) Through Week 156
Description	Safety measure. Monitoring for signs and symptoms of infection-related AEs (e.g., viral, bacterial, or fungal organism, particularly opportunistic infections).
Time Frame	Up to Week 156

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Number of Infusion-Related Reactions Within 24 Hours of PolyTregs Infusion
Description	Any infusion-related adverse events (AEs) Grade 1 or higher that occur within 24 hours of polyclonal Tregs* infusion. This study will grade the severity of AEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
Time Frame	Up to 24 hours post infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Change From Baseline in Pemphigus Disease Area Index (PDAI)
Description	Pemphigus Disease Area Index (PDAI) is a cutaneous and mucosal disease activity assessment performed by the investigator, based on evaluation of lesions in well-defined anatomical locations. The score is weighted for the number and size of lesions, with a score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion(s), are scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranges from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.
Time Frame	From Baseline (Week 0) to Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Change From Baseline in Desmoglein (DSG) Autoantibody Titers
Description	Desmoglein (DSG) autoantibodies serum levels, measured by ELISA (enzyme-linked immunosorbent assay, compared to pre PolyTregs infusion DSG autoantibody levels*. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
Time Frame	Up to Week 156

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Time to Initial Flare/Relapse by Week 156
Description	Time from initiation of polyTregs infusion* to the the time of the appearance of ≥3 new lesions within 1 month that did not heal spontaneously within 1 week, or to the time when there was an extension of lesions that were present at the polyTregs infusion initiation. *Polyclonal Tregs: Ex Vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells.
Time Frame	Up to Week 156

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Number of Participants on a Prednisone Dose ≤10 Milligrams Per Day (mg/Day)
Description	A measure of efficacy. This will be assessed at Weeks 12, 26, 39, 52, 78, 104, 130, and 156.
Time Frame	Up to Week 156

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	52 weeks
Arm/Group Title	Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose
Arm/Group Description	Participants donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs). After two weeks, participants received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10^8 PolyTregs.
All Cause Mortality
	Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose
	Affected / at Risk (%)	# Events
Total	3/4 (75%)
Blood and lymphatic system disorders
Leukopenia	1/4 (25%)	1
Neutropenia	1/4 (25%)	1
Gastrointestinal disorders
Nausea	1/4 (25%)	1
Infections and infestations
COVID-19	1/4 (25%)	1
Eye infection	1/4 (25%)	1
Herpes simplex	1/4 (25%)	1
Viral upper respiratory tract infection	2/4 (50%)	2
Injury, poisoning and procedural complications
Fascial rupture	1/4 (25%)	1
Infusion related reaction	2/4 (50%)	2
Procedural pain	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
Exostosis	1/4 (25%)	1
Nervous system disorders
Paraesthesia	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	1/4 (25%)	1
Upper-airway cough syndrome	1/4 (25%)	1
Skin and subcutaneous tissue disorders
Pemphigus	1/4 (25%)	1
Vascular disorders
Flushing	1/4 (25%)	1
Hypertension	1/4 (25%)	1
Hypotension	1/4 (25%)	1
Orthostatic hypotension	1/4 (25%)	1

Limitations/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.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.