A Phase 1 interventional study of Cohort 1: 1.0 x 10^8 PolyTregs and Cohort 2: 2.5x10^8 PolyTregs in Pemphigus Foliaceus and Pemphigus Vulgaris, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Terminated at 4 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-02-15.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Treatment
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.
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:
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.
Presence of:
Exclusion Criteria:
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:
Doses of background medications at screening:
At or within three months of screening:
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;
Concomitant medical condition that places the subject at risk by participating in this study, including but not limited to:
A single intravenous infusion of 1.0 x 10\^8 PolyTregs will be administered.
Biological: Cohort 1: 1.0 x 10^8 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 1.0 x 10\^8 polyclonal Tregs.
Also known as: Polyclonal Regulatory T Cells, autologous PolyTregs, CD4+CD127lo/negCD25+ PolyTregs
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
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
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.
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.
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.
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.
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.
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.
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
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
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
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.
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.
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
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.
| Milestone | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose | Cohort 2: Polyclonal Treg Infusion (Poly Tregs) High Dose |
|---|---|---|
| Started | 5 | 0 |
| Completed | 5 | 0 |
| Not completed | 0 | 0 |
| Milestone | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose | Cohort 2: Polyclonal Treg Infusion (Poly Tregs) High Dose |
|---|---|---|
| Started | 5 | 0 |
| Completed | 4 | 0 |
| Not completed | 1 | 0 |
| Withdrew: Baseline pemphigus disease area index (pdai) >12, thus ineligible for polytregs infusion. | 1 | 0 |
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.
| Number of Events | Cohort 1: Polyclonal Treg Infusion (PolyTregs) |
|---|---|
| Number of Significant Adverse Events Through Week 52 | 0 |
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.
| Number of Events | Polyclonal Treg Infusion |
|---|---|
| Number of Significant Adverse Events | 0 |
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 Events | Polyclonal Treg Infusion |
|---|---|
| Number of All Adverse Events | 23 |
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 Events | Polyclonal Treg Infusion |
|---|---|
| Number of All NCI-CTCAE Grade 3 or Higher Adverse Events | 0 |
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 Events | Polyclonal Treg Infusion |
|---|---|
| Number of All NCI-CTCAE Grade 3 or Higher Adverse Events | 0 |
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 Events | Polyclonal Treg Infusion |
|---|---|
| Number of All SAEs | 0 |
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 Events | Polyclonal Treg Infusion |
|---|---|
| Number of All Infection Related Events | 7 |
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 Events | Polyclonal Treg Infusion |
|---|---|
| Number of All Infusion Reactions | 5 |
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.
| score | Polyclonal Treg Infusion |
|---|---|
| PDAI Total Activity Score at Week 1 | -1.58 ± 1.179 |
| PDAI Total Activity Score at Week 2 | -1.15 ± 2.845 |
| PDAI Total Activity Score at Week 8 | -1.50 ± 3.032 |
| PDAI Total Activity Score at Week 12 | -0.33 ± 4.392 |
| PDAI Total Activity Score at Week 26 | -2.87 ± 3.092 |
| PDAI Total Activity Score at Week 39 | -1.23 ± 6.823 |
| PDAI Total Activity Score at Week 52 | -3.28 ± 3.323 |
| PDAI Total Activity Score at Week 78 | -5.08 ± 3.496 |
| PDAI Total Activity Score at Week 104 | -5.75 ± 4.070 |
| PDAI Total Activity Score at Week 130 | -3.98 ± 7.617 |
| PDAI Total Activity Score at Week 156 | -7.23 ± 2.700 |
| PDAI Total Damage Score at Week 1 | 0.000 ± 0.816 |
| PDAI Total Damage Score at Week 2 | 0.25 ± 1.258 |
| PDAI Total Damage Score at Week 8 | -1.00 ± 1.414 |
| PDAI Total Damage Score at Week 12 | -1.00 ± 1.414 |
| PDAI Total Damage Score at Week 26 | -0.67 ± 1.155 |
| PDAI Total Damage Score at Week 39 | -0.75 ± 0.957 |
| PDAI Total Damage Score at Week 52 | -0.50 ± 1.291 |
| PDAI Total Damage Score at Week 78 | -1.25 ± 1.893 |
| PDAI Total Damage Score at Week 104 | -1.50 ± 2.380 |
| PDAI Total Damage Score at Week 130 | -1.25 ± 2.630 |
| PDAI Total Damage Score at Week 156 | -1.50 ± 2.380 |
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.
| U/mL | Polyclonal Treg Infusion |
|---|---|
| Desmoglein 1 at Week 1 | 1.00 ± 1.414 |
| Desmoglein 1 at Week 2 | 1.50 ± 2.082 |
| Desmoglein 1 at Week 8 | -0.50 ± 3.873 |
| Desmoglein 1 at Week 12 | 3.50 ± 4.123 |
| Desmoglein 1 at Week 26 | -7.67 ± 17.786 |
| Desmoglein 1 at Week 39 | -8.67 ± 15.144 |
| Desmoglein 1 at Week 52 | -17.00 ± 33.237 |
| Desmoglein 1 at Week 78 | -20.75 ± 57.968 |
| Desmoglein 1 at Week 104 | -33.88 ± 68.940 |
| Desmoglein 1 at Week 130 | -28.75 ± 75.168 |
| Desmoglein 1 at Week 156 | -28.25 ± 79.943 |
| Desmoglein 3 at Week 1 | -1.75 ± 1.708 |
| Desmoglein 3 at Week 2 | -0.50 ± 4.123 |
| Desmoglein 3 at Week 8 | 3.00 ± 9.309 |
| Desmoglein 3 at Week 12 | 1.25 ± 15.457 |
| Desmoglein 3 at Week 26 | 13.33 ± 27.538 |
| Desmoglein 3 at Week 39 | -33.50 ± 36.919 |
| Desmoglein 3 at Week 52 | -30.75 ± 45.966 |
| Desmoglein 3 at Week 78 | -33.25 ± 49.789 |
| Desmoglein 3 at Week 104 | -38.88 ± 50.150 |
| Desmoglein 3 at Week 130 | -34.38 ± 51.406 |
| Desmoglein 3 at Week 156 | -42.25 ± 49.291 |
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.
| participants | Polyclonal Treg Infusion |
|---|---|
| Number of Participants Experiencing a Relapse/Flare | 2 |
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.
| Days | Polyclonal Treg Infusion |
|---|---|
| Time to Relapse (Flare) | 149.0 ± 181.02 |
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.
| participants | Polyclonal Treg Infusion |
|---|---|
| Number taking 0 mg/day at Week 12 | 2 |
| Number taking >0 mg/day and <= 10 mg/day at Week 12 | 2 |
| Number taking >10 mg/day at Week 12 | 0 |
| Number taking 0 mg/day at Week 26 | 2 |
| Number taking >0 mg/day and <= 10 mg/day at Week 26 | 2 |
| Number taking >10 mg/day at Week 26 | 0 |
| Number taking 0 mg/day at Week 39 | 2 |
| Number taking >0 mg/day and <= 10 mg/day at Week 39 | 2 |
| Number taking >10 mg/day at Week 39 | 0 |
| Number taking 0 mg/day at Week 52 | 2 |
| Number taking >0 mg/day and <= 10 mg/day at Week 52 | 2 |
| Number taking >10 mg/day at Week 52 | 0 |
| Number taking 0 mg/day at Week 78 | 2 |
| Number taking >0 mg/day and <= 10 mg/day at Week 78 | 2 |
| Number taking >10 mg/day at Week 78 | 0 |
| Number taking 0 mg/day at Week 104 | 2 |
| Number taking >0 mg/day and <= 10 mg/day at Week 104 | 2 |
| Number taking >10 mg/day at Week 104 | 0 |
| Number taking 0 mg/day at Week 130 | 2 |
| Number taking >0 mg/day and <= 10 mg/day at Week 130 | 2 |
| Number taking >10 mg/day at Week 130 | 0 |
| Number taking 0 mg/day at Week 156 | 2 |
| Number taking >0 mg/day and <= 10 mg/day at Week 156 | 2 |
| Number taking >10 mg/day at Week 156 | 0 |
Collected over Adverse Event data were collected during the following time frames: • From time of signing of informed consent until start of investigational product infusion: all SAEs • From start of investigational product infusion until 24 hours post infusion: all NCI-CTCAE Grade 1 and higher AEs • From 24 hours post-infusion until Week 52: all NCI-CTCAE Grade 2 and higher AEs • From Week 52 until Week 156: all SAEs and all NCI-CTCAE Grade 3 and higher AEs. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Polyclonal Treg Infusion | 0/4 (0%) | 0/4 (0%) | 4/4 (100%) |
| Event | Polyclonal Treg Infusion |
|---|---|
| COVID-19Infections and infestations | 2/4 |
| Viral upper respiratory tract infectionInfections and infestations | 2/4 |
| Infusion related reactionInjury, poisoning and procedural complications | 2/4 |
| LeukopeniaBlood and lymphatic system disorders | 1/4 |
| NeutropeniaBlood and lymphatic system disorders | 1/4 |
| NauseaGastrointestinal disorders | 1/4 |
| Eye infectionInfections and infestations | 1/4 |
| Herpes simplexInfections and infestations | 1/4 |
| Fascial ruptureInjury, poisoning and procedural complications | 1/4 |
| Procedural painInjury, poisoning and procedural complications | 1/4 |
Participants who donated peripheral blood to be processed in a lab that expanded regulatory T cells (Tregs) that, after two weeks, received a single infusion of ex vivo expanded autologous CD4+CD127lo/-CD25+ polyclonal Tregs (PolyTregs). Target cell dose was 1 x 10\^8 PolyTregs.
| Age, Continuous(years) | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose |
|---|---|
| Mean | 38.8 ± 14.2 |
| Sex: Female, Male(Participants) | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose |
|---|---|
| Female | 2 |
| Male | 2 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose |
|---|---|
| Hispanic or Latino | 2 |
| Not Hispanic or Latino | 2 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 4 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose |
|---|---|
| United States | 4 |
| Type of Pemphigus(Participants) | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose |
|---|---|
| Pemphigus Vulgaris | 3 |
| Pemphigus Foliaceus | 1 |
| Age at Diagnosis of Pemphigus(years) | Cohort 1: Polyclonal Treg Infusion (PolyTregs) Low Dose |
|---|---|
| Mean | 33.5 ± 16.9 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
This study is terminated, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
National Institute of Allergy and Infectious Diseases (NIAID)