Pemphigus Foliaceus, Pemphigus Vulgaris
Conditions
Keywords
autologous polyclonal regulatory T cell therapy, PolyTregs, open-label, Phase 1 (safety)
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.
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.
Interventions
BIOLOGICALCohort 1: 1.0 x 10^8 PolyTregs
Each participant will receive a target cell dose of 1.0 x 10\^8 polyclonal Tregs.
BIOLOGICALCohort 2: 2.5x10^8 PolyTregs
Each participant will receive a target cell dose of 2.5x10\^8 polyclonal Tregs.
Sponsors
Autoimmunity Centers of Excellence
Rho Federal Systems Division, Inc.
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of All Adverse Events | From the start of investigational product infusion through Week 156. | An adverse event is any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign, symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research. |
| Number of All NCI-CTCAE Grade 3 or Higher Adverse Events | From the start of investigational product infusion through Week 52. | Adverse events Grade 3 or higher were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0. |
| Number of All SAEs | From the start of investigational product infusion through Week 156. | Number of all serious adverse events, defined as adverse events that result in the following outcomes (21 CFR 312.32(a) and ICH E2A): 1. Death 2. A life-threatening event: An AE or SAR is considered life-threatening if, in the view of either the investigator or DAIT, NIAID, its occurrence places the subject at immediate risk of death. It does not include an AE or SAR that, had it occurred in a more severe form, might have caused death. 3. Inpatient hospitalization or prolongation of existing hospitalization 4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions 5. Congenital anomaly or birth defect 6. Important medical event that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, it may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above. |
| Number of All Infection Related Events | From the start of investigational product infusion through Week 156. | If the adverse event was believed to be caused by a viral, bacterial, or fungal organism, regardless of whether it was treated with antibiotics or not, then it was classified as infection related. |
| Number of All Infusion Reactions | Within 24 hours of infusion | Defined as any adverse reaction of National Cancer Institute - Common Terminology Criteria Grade 1 and higher occurring within 24 hours of infusion. An adverse reaction means any AE caused by a drug. |
| Number of Significant Adverse Events | From the start of investigational product infusion through Week 156. | Number of significant adverse events, defined as any related National Cancer Institute's (NCI's) 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. |
| Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156 | Autoantibodies were measured by Enzyme-Linked Immunosorbent Assays (ELISA). Blood samples were taken from participants at baseline and Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156. If the desmoglein 1 or desmoglein 3 titer was below the limit of detection, the lower limit of detection at the central lab was imputed. The lower limit of detection for both desmoglein 1 and desmoglein 3 was 2.5 U/mL. Change was calculated as the post-baseline value minus the baseline value. A positive difference reflects an increase in the desmoglein titer value over time; a negative difference reflects a decreased desmoglein titer over time. |
| Number of Participants Experiencing a Relapse/Flare | From the start of investigational product infusion through Week 156. | Pemphigus relapses/flares were assessed using the consensus definition of 3 or more new lesions a month that do not heal spontaneously within 1 week or by the extension of established lesions in a patient who has achieved disease control. |
| Time to Relapse (Flare) | From the start of investigational product infusion through Week 156. | Pemphigus relapses/flares will be assessed using the consensus definition of 3 or more new lesions a month that do not heal spontaneously within 1 week or by the extension of established lesions in a patient who has achieved disease control. Time to flare is defined as the number of days between the date of the flare and the date of the investigational product infusion. Only participants who experienced a flare are summarized. |
| Number of Participants on Prednisone Dose ≤10 mg/Day | Weeks 12, 26, 39, 52, 78, 104, 130, and 156 | Defined as the number of participants who were taking 0 mg/day, \>0 and \<=10 mg/day, or \>10 mg/day of prednisone at the time of the associated study visit. |
| Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156 | The PDAI consists of a total activity score and a total damage score. The total activity score is a sum of the activity scores for skin, scalp and mucous membrane. The total activity score can range from 0 to 250. The total damage score is a sum of damage scores for skin and scalp. The total damage score can range from 0 to 13. Higher scores represent higher disease activity. |
Countries
United States
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 signed informed consent on October 10, 2017.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose 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. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Polyclonal Treg Infusion | Baseline Pemphigus Disease Area Index (PDAI) >12, thus ineligible for PolyTregs infusion. | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose |
|---|---|
| Age at Diagnosis of Pemphigus | 33.5 years STANDARD_DEVIATION 16.9 |
| Age, Continuous | 38.8 years STANDARD_DEVIATION 14.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
| Type of Pemphigus Pemphigus Foliaceus | 1 Participants |
| Type of Pemphigus Pemphigus Vulgaris | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
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.
Time frame: Up to Week 52
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Significant Adverse Events Through Week 52 | 0 Number of Events |
Secondary
Change in Desmoglein 1 and 3 Titers by ELISA From Baseline
Autoantibodies were measured by Enzyme-Linked Immunosorbent Assays (ELISA). Blood samples were taken from participants at baseline and Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156. If the desmoglein 1 or desmoglein 3 titer was below the limit of detection, the lower limit of detection at the central lab was imputed. The lower limit of detection for both desmoglein 1 and desmoglein 3 was 2.5 U/mL. Change was calculated as the post-baseline value minus the baseline value. A positive difference reflects an increase in the desmoglein titer value over time; a negative difference reflects a decreased desmoglein titer over time.
Time frame: Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 1 | 1.00 U/mL | Standard Deviation 1.414 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 2 | 1.50 U/mL | Standard Deviation 2.082 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 8 | -0.50 U/mL | Standard Deviation 3.873 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 12 | 3.50 U/mL | Standard Deviation 4.123 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 52 | -17.00 U/mL | Standard Deviation 33.237 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 104 | -33.88 U/mL | Standard Deviation 68.94 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 130 | -28.75 U/mL | Standard Deviation 75.168 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 156 | -28.25 U/mL | Standard Deviation 79.943 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 1 | -1.75 U/mL | Standard Deviation 1.708 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 2 | -0.50 U/mL | Standard Deviation 4.123 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 8 | 3.00 U/mL | Standard Deviation 9.309 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 12 | 1.25 U/mL | Standard Deviation 15.457 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 26 | 13.33 U/mL | Standard Deviation 27.538 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 39 | -33.50 U/mL | Standard Deviation 36.919 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 104 | -38.88 U/mL | Standard Deviation 50.15 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 26 | -7.67 U/mL | Standard Deviation 17.786 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 39 | -8.67 U/mL | Standard Deviation 15.144 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 1 at Week 78 | -20.75 U/mL | Standard Deviation 57.968 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 52 | -30.75 U/mL | Standard Deviation 45.966 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 78 | -33.25 U/mL | Standard Deviation 49.789 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 130 | -34.38 U/mL | Standard Deviation 51.406 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Desmoglein 1 and 3 Titers by ELISA From Baseline | Desmoglein 3 at Week 156 | -42.25 U/mL | Standard Deviation 49.291 |
Secondary
Change in Pemphigus Disease Area Index (PDAI) Score From Baseline
The PDAI consists of a total activity score and a total damage score. The total activity score is a sum of the activity scores for skin, scalp and mucous membrane. The total activity score can range from 0 to 250. The total damage score is a sum of damage scores for skin and scalp. The total damage score can range from 0 to 13. Higher scores represent higher disease activity.
Time frame: Weeks 1, 2, 8, 12, 26, 39, 52, 78, 104, 130, and 156
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 1 | -1.58 score | Standard Deviation 1.179 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 2 | -1.15 score | Standard Deviation 2.845 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 8 | -1.50 score | Standard Deviation 3.032 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 26 | -2.87 score | Standard Deviation 3.092 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 39 | -1.23 score | Standard Deviation 6.823 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 52 | -3.28 score | Standard Deviation 3.323 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 78 | -5.08 score | Standard Deviation 3.496 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 104 | -5.75 score | Standard Deviation 4.07 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 130 | -3.98 score | Standard Deviation 7.617 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 156 | -7.23 score | Standard Deviation 2.7 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 1 | 0.000 score | Standard Deviation 0.816 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 2 | 0.25 score | Standard Deviation 1.258 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 8 | -1.00 score | Standard Deviation 1.414 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 12 | -1.00 score | Standard Deviation 1.414 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 26 | -0.67 score | Standard Deviation 1.155 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 39 | -0.75 score | Standard Deviation 0.957 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 52 | -0.50 score | Standard Deviation 1.291 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 78 | -1.25 score | Standard Deviation 1.893 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 104 | -1.50 score | Standard Deviation 2.38 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Activity Score at Week 12 | -0.33 score | Standard Deviation 4.392 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 130 | -1.25 score | Standard Deviation 2.63 |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Change in Pemphigus Disease Area Index (PDAI) Score From Baseline | PDAI Total Damage Score at Week 156 | -1.50 score | Standard Deviation 2.38 |
Secondary
Number of All Adverse Events
An adverse event is any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign, symptom, or disease, temporally associated with the subject's participation in the research, whether or not considered related to the subject's participation in the research.
Time frame: From the start of investigational product infusion through Week 156.
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of All Adverse Events | 23 Number of Events |
Secondary
Number of All Infection Related Events
If the adverse event was believed to be caused by a viral, bacterial, or fungal organism, regardless of whether it was treated with antibiotics or not, then it was classified as infection related.
Time frame: From the start of investigational product infusion through Week 156.
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of All Infection Related Events | 7 Number of Events |
Secondary
Number of All Infusion Reactions
Defined as any adverse reaction of National Cancer Institute - Common Terminology Criteria Grade 1 and higher occurring within 24 hours of infusion. An adverse reaction means any AE caused by a drug.
Time frame: Within 24 hours of infusion
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of All Infusion Reactions | 5 Number of Events |
Secondary
Number of All NCI-CTCAE Grade 3 or Higher Adverse Events
Adverse events Grade 3 or higher were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0.
Time frame: From the start of investigational product infusion through Week 156.
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of All NCI-CTCAE Grade 3 or Higher Adverse Events | 0 Number of Events |
Secondary
Number of All NCI-CTCAE Grade 3 or Higher Adverse Events
Adverse events Grade 3 or higher were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0.
Time frame: From the start of investigational product infusion through Week 52.
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of All NCI-CTCAE Grade 3 or Higher Adverse Events | 0 Number of Events |
Secondary
Number of All SAEs
Number of all serious adverse events, defined as adverse events that result in the following outcomes (21 CFR 312.32(a) and ICH E2A): 1. Death 2. A life-threatening event: An AE or SAR is considered life-threatening if, in the view of either the investigator or DAIT, NIAID, its occurrence places the subject at immediate risk of death. It does not include an AE or SAR that, had it occurred in a more severe form, might have caused death. 3. Inpatient hospitalization or prolongation of existing hospitalization 4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions 5. Congenital anomaly or birth defect 6. Important medical event that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, it may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: From the start of investigational product infusion through Week 156.
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of All SAEs | 0 Number of Events |
Secondary
Number of Participants Experiencing a Relapse/Flare
Pemphigus relapses/flares were assessed using the consensus definition of 3 or more new lesions a month that do not heal spontaneously within 1 week or by the extension of established lesions in a patient who has achieved disease control.
Time frame: From the start of investigational product infusion through Week 156.
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants Experiencing a Relapse/Flare | 2 participants |
Secondary
Number of Participants on Prednisone Dose ≤10 mg/Day
Defined as the number of participants who were taking 0 mg/day, \>0 and \<=10 mg/day, or \>10 mg/day of prednisone at the time of the associated study visit.
Time frame: Weeks 12, 26, 39, 52, 78, 104, 130, and 156
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking 0 mg/day at Week 12 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >0 mg/day and <= 10 mg/day at Week 12 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >10 mg/day at Week 12 | 0 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >0 mg/day and <= 10 mg/day at Week 78 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >10 mg/day at Week 78 | 0 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking 0 mg/day at Week 104 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >0 mg/day and <= 10 mg/day at Week 104 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >10 mg/day at Week 104 | 0 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking 0 mg/day at Week 130 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >0 mg/day and <= 10 mg/day at Week 130 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >10 mg/day at Week 130 | 0 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking 0 mg/day at Week 156 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >0 mg/day and <= 10 mg/day at Week 156 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >10 mg/day at Week 156 | 0 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking 0 mg/day at Week 26 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >0 mg/day and <= 10 mg/day at Week 26 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >10 mg/day at Week 26 | 0 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking 0 mg/day at Week 39 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >0 mg/day and <= 10 mg/day at Week 39 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >10 mg/day at Week 39 | 0 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking 0 mg/day at Week 52 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >0 mg/day and <= 10 mg/day at Week 52 | 2 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking >10 mg/day at Week 52 | 0 participants |
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Participants on Prednisone Dose ≤10 mg/Day | Number taking 0 mg/day at Week 78 | 2 participants |
Secondary
Number of Significant Adverse Events
Number of significant adverse events, defined as any related National Cancer Institute's (NCI's) 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.
Time frame: From the start of investigational product infusion through Week 156.
Population: Participants donated peripheral blood to be processed in a lab that expanded the T cells (Tregs) to a target of 1 x 10\^8 PolyTregs/mL. After two weeks, the participant was infused with their own expanded Tregs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Number of Significant Adverse Events | 0 Number of Events |
Secondary
Time to Relapse (Flare)
Pemphigus relapses/flares will be assessed using the consensus definition of 3 or more new lesions a month that do not heal spontaneously within 1 week or by the extension of established lesions in a patient who has achieved disease control. Time to flare is defined as the number of days between the date of the flare and the date of the investigational product infusion. Only participants who experienced a flare are summarized.
Time frame: From the start of investigational product infusion through Week 156.
Population: Participants who initiated the investigational product infusion and experienced a flare between investigational product infusion and Week 156.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Polyclonal Treg Infusion (PolyTregs) | Time to Relapse (Flare) | 149.0 Days | Standard Deviation 181.02 |