Adult Living Donor Kidney Transplant Recipients, Kidney Transplant, Living Kidney Donor, Renal Transplant
Conditions
Keywords
graft inflammation, Treg, polyclonally expanded Tregs (polyTregs), calcineurin inhibitors (CNIs), mTOR inhibitors
Brief summary
The purpose of this study is: * To see if polyTregs can reduce inflammation in a transplanted kidney. * To find out what effects, good or bad, polyTregs will have in the kidney recipient. * To find out what effects, good or bad, taking everolimus after polyTregs will have in the kidney recipient.
Detailed description
Inflammation occurs when the body's defense system recognizes a foreign object (such as a transplanted kidney), and responds by sending white blood cells to attack the foreign object. These cells and the substances they produce can damage the transplanted kidney. There is currently no standard treatment for inflammation in the kidney; some transplant centers do not treat inflammation at all. Rejection is a more severe form of inflammation and injury. Both inflammation and rejection are diagnosed by looking at a piece of kidney (a kidney biopsy) under a microscope. Kidneys that have inflammation and/or rejection do not work as well or last as long as kidneys without injury. People who have a transplant take immunosuppressive drugs (IS) to prevent inflammation and rejection. Although kidney transplant recipients usually do well in the first five years after transplant, transplant researchers are interested in finding ways to prevent inflammation and rejection without IS, or with lower doses of IS in order to avoid side effects. While some white blood cells cause inflammation, other types of white blood cells, called T regulatory cells (Tregs), can control inflammation. Tregs may have an important role in controlling or preventing inflammation and rejection. A person's Tregs can be grown in the laboratory to increase their number (polyTreg). These Tregs can be given back through a needle placed in a vein (IV). PolyTregs, when given to the recipient, might reduce inflammation in the transplanted kidney. However, this effect has not yet been shown. One of the IS drugs used in kidney transplant is Everolimus. Everolimus has been shown to help Tregs survive better than other types of IS drugs. This is a randomized open-label trial to determine the safety and efficacy of a single dose of autologous polyTregs in renal transplant recipients with subclinical inflammation (SCI) in the 3 to 7 months post-transplant allograft protocol biopsy compared to control patients treated with CNI-based immunosuppression. The efficacy of the Treg therapy will be assessed by the reduction of graft inflammation on biopsies performed at 7 months after study group allocation compared to the eligibility biopsy.
Interventions
BIOLOGICALPolyclonal Regulatory T Cells
Participants randomized to polyTregs group will receive a single infusion of 550 ± 450 x 10\^6 polyTregs.
DRUGEverolimus
DRUGTacrolimus
DRUGMycophenolate mofetil
All enrolled participants will be on MMF (or MPA below) at the time of study entry at a minimum dose of 1000mg per day.
DRUGMycophenolic acid
All enrolled participants will be on MPA (or MMF above) at the time of study entry at a minimum dose of 720mg per day.
DRUGAcetaminophen
650 mg acetaminophen, administered 30-60 minutes prior to infusion as pre-medication.
DRUGDiphenhydramine
25-50 mg diphenhydramine intravenously or by mouth, administered 30-60 minutes prior to infusion as pre-medication.
PROCEDUREBiopsy, Kidney
PROCEDUREBlood Draw
PROCEDURELeukapheresis
PROCEDUREIS regimen conversion
Conversion from Tacrolimus, a calcineurin inhibitors (CNI), to Everolimus, an mTOR inhibitor.
Sponsors
Clinical Trials in Organ Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Individuals who meet all of the following criteria are eligible for enrollment as study participants: 1. Subject must be able to understand and provide informed consent; 2. Age ≥18 years of age at the time of study entry; 3. Recipients of non- Human Leukocyte Antigen (HLA) identical living or deceased renal transplants; 4. Protocol renal allograft biopsy at 5 months (± 8 weeks) after transplantation with Banff i1 and/or ti1 with concomitant t scores t0, t1,t2 or t3; Banff i2 and/or ti2 with concomitant t scores t0 or t1; and without v \> 0, \[ptc + g\] ≥2, C4d \>1 (by immunofluorescence, IF), or C4d \> 0 (by immunohistochemistry, IHC); confirmed by central pathologist. Subjects must not be treated for pathologic criteria (e.g. steroids). 5. Estimated glomerular filtration rate (eGFR) ≥30 ml/min at the time of study entry; 6. Maintenance immunosuppression consisting of tacrolimus, MMF/MPA (≥1000 mg/720 mg daily) ± prednisone (≤10 mg/day); 7. Current immunizations including TdAP, hepatitis B, pneumococcal and seasonal influenza vaccines prior to study treatment, completed prior to randomization and no less than 14 days prior to planned manufacturing collection; 8. Documented Hepatitis B (HB) serologies must be: 1. Positive HB surface antibody, negative HB core antibody and negative HB surface antigen for recipients immune to hepatitis B 2. Negative HB surface antibody, negative HB core antibody and negative HB surface antigen for non-immune/ HBV naïve recipients provided donor had negative HB core antibody and negative HB surface antigen at the time of donation. 9. Negative TB test (PPD, interferon-gamma release assay, ELISPOT testing) within 1 year prior to enrollment. Subjects with a history of TB (positive TB test without active infection) must have completed one of the latent TB infection treatment regimens endorsed by the CDC (Division of TB Elimination, 2016). Alternative regimens for latent TB infection eradication will be adjudicated by the site's infectious disease specialist. 10. Female subjects of childbearing potential must have reviewed the Mycophenolate Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) and have a negative pregnancy test upon study entry (Reference:https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm318880.htm); and 11. Female subjects with child-bearing potential, must agree to use FDA approved methods of birth control for the duration of the study; subjects must consult with their physician and determine the most suitable method(s) that are greater than 80% effective (http://www.fda.gov/birthcontrol). Treg Infusion Inclusion Criteria: 1. Individuals randomized to the polyTreg and darTreg groups who continue to meet all of the enrollment criteria; and 2. Negative SARS-COV2 by RTP-PCR testing within 1 week of Treg infusion. mTOR Conversion Inclusion Criteria: Individuals who meet all of these criteria are eligible for mTOR conversion: 1. Received at least 300 x 10\^6 polyTreg infusion; 2. Resolution of inflammation on the 2 week post-infusion biopsy as compared to the baseline biopsy, confirmed by central pathologist.
Exclusion criteria
Individuals who meet any of these criteria are not eligible for enrollment as study participants: 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol; 2. History of malignancy; except adequately treated basal cell carcinoma; 3. History of graft loss from acute rejection within 1 year after any previous transplant; 4. History of transplant renal artery stenosis; 5. History of cellular rejection prior to enrollment that did not respond to steroids and/or subsequent creatinine after treatment for rejection greater than 15% above baseline; 6. Known hypersensitivity to mTOR inhibitors or contraindication to everolimus (including history of wound healing complications); 7. Any chronic illness requiring uninterrupted anti-coagulation after kidney transplantation; 8. Post-transplant DSA \>5000 MFI or post-transplant treatment with IVIg for DSA. * Note: Enrolled subjects with post-transplant DSA \>2000 MFI will not be eligible for mTOR conversion. 9. Positive HIV 1 or HIV 2 serology prior to transplantation; 10. Positive HBSAg or HBcAb serology; 11. Proteinuria with urine protein-to-creatinine ratio \> 1.0 g/g; 12. Any condition requiring chronic use of corticosteroids \>10mg/day at the time of study entry; 13. Subjects requiring treatment for pathologic findings on study eligibility biopsy (see inclusion 5). 14. Active infection at the time of study entry; 15. History of active TB or latent TB without adequate treatment; 16. Serum BK virus \>1,000 copies/ml by Polymerase Chain Reaction (PCR) at the time of study entry; 17. Hematocrit \<27%; Absolute Neutrophil Count (ANC) \< 1,000/μL; and/or lymphocyte count \<500/μL at the time of study entry; 18. Participation in any other studies with investigational drugs or regimens in the preceding year; 19. Any condition or prior treatment which, in the opinion of the investigator, precludes study participation. 20. Unable to provide adequate biopsy specimen (paraffin embedded formalin fixed) from eligibility biopsy (3-7 months post -transplant) for quantitative analysis. 21. Epstein-Barr virus (EBV) naïve recipient of a kidney from an EBV positive donor; and/or historically EBV naïve recipient with primary EBV infection at the time of screening (e.g., anti-VCA IgM positive and EBNA negative), a positive EBV PCR. 22. Hepatitis C Virus AB positive subjects with negative HCV PCR are eligible if they have spontaneously cleared infection or are in sustained virologic remission for at least 12 weeks after treatment. 23. Positive SARS-CoV2 testing by RT-PCR Treg Infusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Banff 2A or Higher Acute Cell-mediated Rejection and/or Acute Antibody Mediated Rejection | 405 days post-group allocation | Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 2A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. Antibody mediated rejection was defined as diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury. |
| Timing of Banff 2A or Higher Acute Cell-mediated Rejection and/or Acute Antibody Mediated Rejection | 405 days post-group allocation | Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 2A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2IA, 2IB, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. Antibody mediated rejection was defined as diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury. |
| Incidence of Study Defined Grade 3 or Higher Infection | 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups | This outcome measure includes infections reported as adverse events. Severe infection was defined in the study as a Grade 3 or higher infection. Severity is graded as 1 through 5, with 1 being least severe to 5 being most severe. Grade 3 is any infection associated with hemodynamic compromise requiring pressors; any infection necessitating ICU level of care; any infection necessitating operative intervention; any infection involving the central nervous system; any infection with a positive fungal blood culture; any proven or probable aspergillus infection; any tissue invasive fungal infection; any pneumocystis jiroveci infection. Grade 4 is any life-threatening infection. Grade 5 is any infection resulting in death. |
| Timing of Study Defined Grade 3 or Higher Infection | 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups. | This outcome measure includes infections reported as adverse events. Severe infection was defined in the study as a Grade 3 or higher infection. Severity is graded as 1 through 5, with 1 being least severe to 5 being most severe. Grade 3 is any infection associated with hemodynamic compromise requiring pressors; any infection necessitating ICU level of care; any infection necessitating operative intervention; any infection involving the central nervous system; any infection with a positive fungal blood culture; any proven or probable aspergillus infection; any tissue invasive fungal infection; any pneumocystis jiroveci infection. Grade 4 is any life-threatening infection. Grade 5 is any infection resulting in death. |
| Percent Change in Inflammation | At baseline biopsy and at 7 months post-group allocation | The change in inflammation was measured by the percentage area of the renal cortex occupied by inflammatory cells on biopsy 7 months after group allocation. This change was expressed as the percent change relative to the baseline biopsy. The measurements were obtained using computer-assisted quantitative image analysis. |
| Immunologic Profiles of Kidney Transplant Recipients | At 2 weeks post-polyTregs infusion (for polyTregs infusion group) and at 7 months post-group allocation (both groups) | CRM (Common Response Module) score is a geometric mean of CRM gene expression. This score is used to identify evidence of rejection or inflammation in participants at the time of biopsy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Acute Rejection Using Banff Grading | 405 days post-group allocation | Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 1A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. |
| Severity of Acute Rejection Using Banff Grading | 405 days post-group allocation | Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 1A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. |
| Timing of Acute Rejection Using Banff Grading | 405 days post-group allocation | Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 1A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. |
| Incidence of BK Viremia | 405 days post-group allocation | BK viremia was determined using locally reported serum PCR results. PCR results reported as positive and \>0 copies/mL were considered as meeting the endpoint. Only positive results following Treg infusion were considered for participants in the polyTregs and darTregs groups. |
| Timing of BK Viremia | 405 days post-group allocation | BK viremia was determined using locally reported serum PCR results. PCR results reported as positive and \>0 copies/mL were considered as meeting the endpoint. Only positive results following Treg infusion were considered for participants in the polyTregs and darTregs groups. |
| Incidence of Cytomegalovirus (CMV) Reactivation | 405 days post-group allocation | CMV reactivation was defined as CMV viremia and determined using locally reported serum, plasma, or whole blood PCR results. PCR results reported as \>0 IU/mL were considered as meeting the endpoint. Only positive results following Treg infusion were considered for participants in the polyTregs and darTregs groups. |
| Timing of CMV Reactivation | 405 days post-group allocation | CMV reactivation was defined as CMV viremia and determined using locally reported serum, plasma, or whole blood PCR results. PCR results reported as \>0 IU/mL were considered as meeting the endpoint. Only positive results following Treg infusion were considered for participants in the polyTregs and darTregs groups. |
| Incidence of polyTregs Infusion Reactions | 365 days after Treg infusion for the participants in the polyTregs group | An infusion reaction is characterized by an adverse reaction to the infusion of pharmacological substance, as defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 set forth by the National Cancer Institute. |
| Timing of > 10% Decrease in eGFR Compared to Baseline | 405 days post-group allocation | Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicate moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or end stage kidney failure. The percent change in eGFR was calculated at each post-baseline timepoint as \[(post-baseline eGFR minus baseline (i.e., screening) eGFR) divided by baseline eGFR\] multiplied by 100 and rounded to the nearest hundredth for each participant. A participant was considered to have met the endpoint if at least one instance of a greater than 10% decrease from baseline was observed. |
| Incidence of Acute Rejection After Converting to mTOR Therapy Following polyTregs Infusion | 69 days post-group allocation to 405 days post-group allocation | Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 2A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. |
| Timing of Acute Rejection After Converting to mTOR Therapy Following polyTregs Infusion | 69 days post-group allocation to 405 days post-group allocation | Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 2A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. |
| Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy | Baseline biopsy to week 2 kidney biopsy | The change in inflammation was measured by the percentage area of the renal cortex occupied by inflammatory cells on biopsy 2 weeks after polyTregs infusion. This change was expressed as the percent change relative to the baseline biopsy. The measurements were obtained using computer-assisted quantitative image analysis. |
| Proportion of Participants Exhibiting >=50% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy | Baseline biopsy to week 2 kidney biopsy | The change in inflammation was measured by the percentage area of the renal cortex occupied by inflammatory cells on biopsy 2 weeks after polyTregs infusion. This change was expressed as the percent change relative to the baseline biopsy. The measurements were obtained using computer-assisted quantitative image analysis. |
| Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the 6 Month Kidney Biopsy | Baseline biopsy to 7 months post-group allocation | The change in inflammation was measured by the percentage area of the renal cortex occupied by inflammatory cells on biopsy 7 months after study group allocation. This change was expressed as the percent change relative to the baseline biopsy. The measurements were obtained using computer-assisted quantitative image analysis. |
| Incidence of > 10% Decrease in Estimated Glomerular Filtration Rate (eGFR) Compared to Baseline | 405 days post-group allocation | Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicate moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or end stage kidney failure. The percent change in eGFR was calculated at each post-baseline timepoint as \[(post-baseline eGFR minus baseline (i.e., screening) eGFR) divided by baseline eGFR\] multiplied by 100 and rounded to the nearest hundredth for each participant. A participant was considered to have met the endpoint if at least one instance of a greater than 10% decrease from baseline was observed. |
| Severity of polyTregs Infusion Reactions | 365 days after Treg infusion for the participants in the polyTregs group | Severity of infusion reactions were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 set forth by the National Cancer Institute. Severity of adverse events is graded as 1 through 5, with 1 being least severe to 5 being most severe. |
| Timing of polyTregs Infusion Reactions | 365 days after Treg infusion for the participants in the polyTregs group | An infusion reaction is characterized by an adverse reaction to the infusion of pharmacological substance, as defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 set forth by the National Cancer Institute. |
| Incidence of Culture-proven and Clinically Diagnosed Infection. | 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups | A culture-proven and clinically diagnosed infection in this study was defined as any locally reported infection due to bacterial organism, due to fungal organism, due to CMV, or which met adverse event criteria, except for COVID-19. |
| Severity of Culture-proven and Clinically Diagnosed Infection | 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups | A culture-proven and clinically diagnosed infection was defined as any locally reported infection due to bacterial organism, fungal organism, CMV, or which met adverse event criteria, except for COVID-19. Severe infection was defined in the study as a Grade 3 or higher infection. Severity is graded as 1 through 5 with 1 being least severe to 5 being most severe. Grade 3 is any infection associated with hemodynamic compromise requiring pressors; any infection necessitating ICU level of care; any infection necessitating operative intervention; any infection involving the central nervous system; any infection with a positive fungal blood culture; any proven or probable aspergillus infection; any tissue invasive fungal infection; any pneumocystis jiroveci infection. Grade 4 is any life-threatening infection. Grade 5 is any infection resulting in death. If a culture proven and clinically diagnosed infection did not qualify for AE reporting, then it did not have a severity grade. |
| Timing of Culture-proven and Clinically Diagnosed Infection | 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups | A culture-proven and clinically diagnosed infection in this study was defined as any locally reported infection due to bacterial organism, fungal organism, CMV, or which met adverse event criteria, except for COVID-19. |
Countries
United States
Participant flow
Recruitment details
27 adult, kidney transplant candidates were enrolled across 7 US sites between September 2016 and May 2022. Of these 27 enrolled transplant candidates, 18 participants were randomized and 16 initiated study treatment. Additionally, 5 living donors consented at 2 US sites between September 2016 and September 2018.
Pre-assignment details
Potential participants signed informed consent before undergoing any study procedures. Screening criteria, including results from a 5 month post-transplant standard of care biopsy, were evaluated to determine study eligibility and candidacy for randomization. Living donors were asked to consent for a blood draw and minimal medical information.
Participants by arm
| Arm | Count |
|---|---|
| Maintenance Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention. | 8 |
| polyTregs Participants in the polyclonally expanded regulatory T cells (polyTregs) group received a single infusion of 550 ± 450 x 10⁶ polyTregs administered via a peripheral intravenous line primed with saline by gravity in approximately 20 to 30 minutes. | 7 |
| darTregs Participants in the donor alloantigen reactive regulatory T cells (darTregs) group received a single infusion of 400 ± 100 x 10⁶ darTregs administered via a peripheral intravenous line primed with saline by gravity in approximately 20 to 30 minutes. | 1 |
| Enrolled, Living Donor Living donors of the prospective transplant recipient were consented and enrolled into the study. | 5 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Failure to manufacture cellular product | 0 | 0 | 5 | 0 | 0 |
| Overall Study | Infusion canceled for active infection | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Screen failures | 0 | 0 | 0 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 4 | 0 |
Baseline characteristics
| Characteristic | Maintenance | polyTregs | darTregs | Enrolled, Living Donor | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 6 Participants | 1 Participants | 4 Participants | 18 Participants |
| Age, Continuous | 47.5 years STANDARD_DEVIATION 11.78 | 52.1 years STANDARD_DEVIATION 11.94 | 58.0 years STANDARD_DEVIATION 0 | 48.0 years STANDARD_DEVIATION 17.66 | 49.7 years STANDARD_DEVIATION 12.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 4 Participants | 1 Participants | 4 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 0 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) White | 5 Participants | 2 Participants | 1 Participants | 2 Participants | 10 Participants |
| Region of Enrollment United States | 8 participants | 7 participants | 1 participants | 5 participants | 21 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 0 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 1 Participants | 2 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 2 | 0 / 5 |
| other Total, other adverse events | 2 / 8 | 4 / 8 | 0 / 2 | 0 / 5 |
| serious Total, serious adverse events | 3 / 8 | 4 / 8 | 1 / 2 | 0 / 5 |
Outcome results
Primary
Immunologic Profiles of Kidney Transplant Recipients
CRM (Common Response Module) score is a geometric mean of CRM gene expression. This score is used to identify evidence of rejection or inflammation in participants at the time of biopsy.
Time frame: At 2 weeks post-polyTregs infusion (for polyTregs infusion group) and at 7 months post-group allocation (both groups)
Population: Data were not collected for this endpoint.
Primary
Incidence of Banff 2A or Higher Acute Cell-mediated Rejection and/or Acute Antibody Mediated Rejection
Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 2A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. Antibody mediated rejection was defined as diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated study treatment, subset to participants with available central pathology read data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Incidence of Banff 2A or Higher Acute Cell-mediated Rejection and/or Acute Antibody Mediated Rejection | 0 Participants |
| polyTregs | Incidence of Banff 2A or Higher Acute Cell-mediated Rejection and/or Acute Antibody Mediated Rejection | 0 Participants |
| darTregs | Incidence of Banff 2A or Higher Acute Cell-mediated Rejection and/or Acute Antibody Mediated Rejection | 0 Participants |
Primary
Incidence of Study Defined Grade 3 or Higher Infection
This outcome measure includes infections reported as adverse events. Severe infection was defined in the study as a Grade 3 or higher infection. Severity is graded as 1 through 5, with 1 being least severe to 5 being most severe. Grade 3 is any infection associated with hemodynamic compromise requiring pressors; any infection necessitating ICU level of care; any infection necessitating operative intervention; any infection involving the central nervous system; any infection with a positive fungal blood culture; any proven or probable aspergillus infection; any tissue invasive fungal infection; any pneumocystis jiroveci infection. Grade 4 is any life-threatening infection. Grade 5 is any infection resulting in death.
Time frame: 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups
Population: Intent-to-treat population who initiated study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Incidence of Study Defined Grade 3 or Higher Infection | 2 Participants |
| polyTregs | Incidence of Study Defined Grade 3 or Higher Infection | 3 Participants |
| darTregs | Incidence of Study Defined Grade 3 or Higher Infection | 1 Participants |
p-value: 0.425Fisher Exact
Primary
Percent Change in Inflammation
The change in inflammation was measured by the percentage area of the renal cortex occupied by inflammatory cells on biopsy 7 months after group allocation. This change was expressed as the percent change relative to the baseline biopsy. The measurements were obtained using computer-assisted quantitative image analysis.
Time frame: At baseline biopsy and at 7 months post-group allocation
Population: Intent-to-treat population who initiated treatment, subset to participants from the Maintenance and polyTregs groups with available LCA data from the biopsy 7 months post-group allocation. darTregs group excluded from efficacy analysis per the protocol and statistical analysis plan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maintenance | Percent Change in Inflammation | -59.16 Percent change |
| polyTregs | Percent Change in Inflammation | -78.95 Percent change |
p-value: 0.201Kruskal-Wallis
Primary
Timing of Banff 2A or Higher Acute Cell-mediated Rejection and/or Acute Antibody Mediated Rejection
Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 2A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2IA, 2IB, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection. Antibody mediated rejection was defined as diffusely positive staining for C4d, presence of circulating anti-donor antibodies, and morphologic evidence of acute tissue injury.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated study treatment, subset to participants with available central pathology read data who had severe acute cell-mediated rejection and/or acute antibody mediated rejection. No participants met the criteria for inclusion in this analysis population.
Primary
Timing of Study Defined Grade 3 or Higher Infection
This outcome measure includes infections reported as adverse events. Severe infection was defined in the study as a Grade 3 or higher infection. Severity is graded as 1 through 5, with 1 being least severe to 5 being most severe. Grade 3 is any infection associated with hemodynamic compromise requiring pressors; any infection necessitating ICU level of care; any infection necessitating operative intervention; any infection involving the central nervous system; any infection with a positive fungal blood culture; any proven or probable aspergillus infection; any tissue invasive fungal infection; any pneumocystis jiroveci infection. Grade 4 is any life-threatening infection. Grade 5 is any infection resulting in death.
Time frame: 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups.
Population: Intent-to-treat population who initiated study treatment and experienced a severe infection
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maintenance | Timing of Study Defined Grade 3 or Higher Infection | 179.0 Days |
| polyTregs | Timing of Study Defined Grade 3 or Higher Infection | 116.0 Days |
| darTregs | Timing of Study Defined Grade 3 or Higher Infection | 84.0 Days |
p-value: 0.7Kruskal-Wallis
Secondary
Incidence of > 10% Decrease in Estimated Glomerular Filtration Rate (eGFR) Compared to Baseline
Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicate moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or end stage kidney failure. The percent change in eGFR was calculated at each post-baseline timepoint as \[(post-baseline eGFR minus baseline (i.e., screening) eGFR) divided by baseline eGFR\] multiplied by 100 and rounded to the nearest hundredth for each participant. A participant was considered to have met the endpoint if at least one instance of a greater than 10% decrease from baseline was observed.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Incidence of > 10% Decrease in Estimated Glomerular Filtration Rate (eGFR) Compared to Baseline | 5 Participants |
| polyTregs | Incidence of > 10% Decrease in Estimated Glomerular Filtration Rate (eGFR) Compared to Baseline | 6 Participants |
| darTregs | Incidence of > 10% Decrease in Estimated Glomerular Filtration Rate (eGFR) Compared to Baseline | 1 Participants |
Secondary
Incidence of Acute Rejection After Converting to mTOR Therapy Following polyTregs Infusion
Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 2A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection.
Time frame: 69 days post-group allocation to 405 days post-group allocation
Population: Intent-to-treat population who initiated treatment, subset to participants who received the polyTregs infusion and converted to mTOR therapy. No participants met the criteria for inclusion in this analysis population.
Secondary
Incidence of Acute Rejection Using Banff Grading
Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 1A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated study treatment, subset to participants with available central pathology read data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Incidence of Acute Rejection Using Banff Grading | 0 Participants |
| polyTregs | Incidence of Acute Rejection Using Banff Grading | 0 Participants |
| darTregs | Incidence of Acute Rejection Using Banff Grading | 0 Participants |
Secondary
Incidence of BK Viremia
BK viremia was determined using locally reported serum PCR results. PCR results reported as positive and \>0 copies/mL were considered as meeting the endpoint. Only positive results following Treg infusion were considered for participants in the polyTregs and darTregs groups.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Incidence of BK Viremia | 0 Participants |
| polyTregs | Incidence of BK Viremia | 1 Participants |
| darTregs | Incidence of BK Viremia | 0 Participants |
Secondary
Incidence of Culture-proven and Clinically Diagnosed Infection.
A culture-proven and clinically diagnosed infection in this study was defined as any locally reported infection due to bacterial organism, due to fungal organism, due to CMV, or which met adverse event criteria, except for COVID-19.
Time frame: 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups
Population: Intent-to-treat population who initiated study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Incidence of Culture-proven and Clinically Diagnosed Infection. | 2 Participants |
| polyTregs | Incidence of Culture-proven and Clinically Diagnosed Infection. | 3 Participants |
| darTregs | Incidence of Culture-proven and Clinically Diagnosed Infection. | 1 Participants |
Secondary
Incidence of Cytomegalovirus (CMV) Reactivation
CMV reactivation was defined as CMV viremia and determined using locally reported serum, plasma, or whole blood PCR results. PCR results reported as \>0 IU/mL were considered as meeting the endpoint. Only positive results following Treg infusion were considered for participants in the polyTregs and darTregs groups.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Incidence of Cytomegalovirus (CMV) Reactivation | 0 Participants |
| polyTregs | Incidence of Cytomegalovirus (CMV) Reactivation | 0 Participants |
| darTregs | Incidence of Cytomegalovirus (CMV) Reactivation | 1 Participants |
Secondary
Incidence of polyTregs Infusion Reactions
An infusion reaction is characterized by an adverse reaction to the infusion of pharmacological substance, as defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 set forth by the National Cancer Institute.
Time frame: 365 days after Treg infusion for the participants in the polyTregs group
Population: Intent-to-treat population, subset to participants who received the polyTregs infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| polyTregs | Incidence of polyTregs Infusion Reactions | 0 Participants |
Secondary
Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the 6 Month Kidney Biopsy
The change in inflammation was measured by the percentage area of the renal cortex occupied by inflammatory cells on biopsy 7 months after study group allocation. This change was expressed as the percent change relative to the baseline biopsy. The measurements were obtained using computer-assisted quantitative image analysis.
Time frame: Baseline biopsy to 7 months post-group allocation
Population: Intent-to-treat population who initiated treatment, subset to participants with available LCA data from the biopsy 7 months post-group allocation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the 6 Month Kidney Biopsy | 3 Participants |
| polyTregs | Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the 6 Month Kidney Biopsy | 5 Participants |
| darTregs | Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the 6 Month Kidney Biopsy | 1 Participants |
Secondary
Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy
The change in inflammation was measured by the percentage area of the renal cortex occupied by inflammatory cells on biopsy 2 weeks after polyTregs infusion. This change was expressed as the percent change relative to the baseline biopsy. The measurements were obtained using computer-assisted quantitative image analysis.
Time frame: Baseline biopsy to week 2 kidney biopsy
Population: Intent-to-treat population who initiated treatment, subset to participants with available LCA data from the Week 2 biopsy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy | 0 Participants |
| polyTregs | Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy | 2 Participants |
| darTregs | Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy | 0 Participants |
Secondary
Proportion of Participants Exhibiting >=50% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy
The change in inflammation was measured by the percentage area of the renal cortex occupied by inflammatory cells on biopsy 2 weeks after polyTregs infusion. This change was expressed as the percent change relative to the baseline biopsy. The measurements were obtained using computer-assisted quantitative image analysis.
Time frame: Baseline biopsy to week 2 kidney biopsy
Population: Intent-to-treat population who initiated treatment, subset to participants with available LCA data from the Week 2 biopsy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Maintenance | Proportion of Participants Exhibiting >=50% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy | 0 Participants |
| polyTregs | Proportion of Participants Exhibiting >=50% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy | 1 Participants |
| darTregs | Proportion of Participants Exhibiting >=50% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy | 0 Participants |
Secondary
Severity of Acute Rejection Using Banff Grading
Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 1A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated study treatment, subset to participants with available central pathology read data and who experienced acute rejection. No participants met the criteria for inclusion in this analysis population.
Secondary
Severity of Culture-proven and Clinically Diagnosed Infection
A culture-proven and clinically diagnosed infection was defined as any locally reported infection due to bacterial organism, fungal organism, CMV, or which met adverse event criteria, except for COVID-19. Severe infection was defined in the study as a Grade 3 or higher infection. Severity is graded as 1 through 5 with 1 being least severe to 5 being most severe. Grade 3 is any infection associated with hemodynamic compromise requiring pressors; any infection necessitating ICU level of care; any infection necessitating operative intervention; any infection involving the central nervous system; any infection with a positive fungal blood culture; any proven or probable aspergillus infection; any tissue invasive fungal infection; any pneumocystis jiroveci infection. Grade 4 is any life-threatening infection. Grade 5 is any infection resulting in death. If a culture proven and clinically diagnosed infection did not qualify for AE reporting, then it did not have a severity grade.
Time frame: 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups
Population: Intent-to-treat population who initiated study treatment, subset to those with culture-proven and clinically diagnosed infections
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Maintenance | Severity of Culture-proven and Clinically Diagnosed Infection | Grade 3 | 2 Participants |
| Maintenance | Severity of Culture-proven and Clinically Diagnosed Infection | No Grade | 0 Participants |
| polyTregs | Severity of Culture-proven and Clinically Diagnosed Infection | Grade 3 | 2 Participants |
| polyTregs | Severity of Culture-proven and Clinically Diagnosed Infection | No Grade | 1 Participants |
| darTregs | Severity of Culture-proven and Clinically Diagnosed Infection | Grade 3 | 1 Participants |
| darTregs | Severity of Culture-proven and Clinically Diagnosed Infection | No Grade | 0 Participants |
Secondary
Severity of polyTregs Infusion Reactions
Severity of infusion reactions were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 set forth by the National Cancer Institute. Severity of adverse events is graded as 1 through 5, with 1 being least severe to 5 being most severe.
Time frame: 365 days after Treg infusion for the participants in the polyTregs group
Population: Intent-to-treat population, subset to participants who received the polyTregs infusion and had a polyTregs infusion reaction. No participants met the criteria for inclusion in this analysis population.
Secondary
Timing of > 10% Decrease in eGFR Compared to Baseline
Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicate moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or end stage kidney failure. The percent change in eGFR was calculated at each post-baseline timepoint as \[(post-baseline eGFR minus baseline (i.e., screening) eGFR) divided by baseline eGFR\] multiplied by 100 and rounded to the nearest hundredth for each participant. A participant was considered to have met the endpoint if at least one instance of a greater than 10% decrease from baseline was observed.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated treatment, subset to participants who had a \>10% decrease in eGFR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maintenance | Timing of > 10% Decrease in eGFR Compared to Baseline | 51.0 Days |
| polyTregs | Timing of > 10% Decrease in eGFR Compared to Baseline | 53.0 Days |
| darTregs | Timing of > 10% Decrease in eGFR Compared to Baseline | 44.0 Days |
Secondary
Timing of Acute Rejection After Converting to mTOR Therapy Following polyTregs Infusion
Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 2A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection.
Time frame: 69 days post-group allocation to 405 days post-group allocation
Population: Intent-to-treat population who initiated treatment, subset to participants who received the polyTregs infusion, converted to mTOR therapy, and had an acute rejection event. No participants met the criteria for inclusion in this analysis population.
Secondary
Timing of Acute Rejection Using Banff Grading
Acute cell-mediated rejection was defined using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to 1A were determined to have met the endpoint. Severity is graded as 1A, 1B, 2A, 2B, or 3, with 1A being the mildest form of cellular rejection and 3 being the most severe form of cellular rejection.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated study treatment, subset to participants with available central pathology read data and who experienced acute rejection. No participants met the criteria for inclusion in this analysis population.
Secondary
Timing of BK Viremia
BK viremia was determined using locally reported serum PCR results. PCR results reported as positive and \>0 copies/mL were considered as meeting the endpoint. Only positive results following Treg infusion were considered for participants in the polyTregs and darTregs groups.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated treatment, subset to participants who experienced BK viremia.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| polyTregs | Timing of BK Viremia | 365.00 Days |
Secondary
Timing of CMV Reactivation
CMV reactivation was defined as CMV viremia and determined using locally reported serum, plasma, or whole blood PCR results. PCR results reported as \>0 IU/mL were considered as meeting the endpoint. Only positive results following Treg infusion were considered for participants in the polyTregs and darTregs groups.
Time frame: 405 days post-group allocation
Population: Intent-to-treat population who initiated treatment, subset to participants who experienced CMV reactivation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| darTregs | Timing of CMV Reactivation | 84.0 Days |
Secondary
Timing of Culture-proven and Clinically Diagnosed Infection
A culture-proven and clinically diagnosed infection in this study was defined as any locally reported infection due to bacterial organism, fungal organism, CMV, or which met adverse event criteria, except for COVID-19.
Time frame: 405 days after randomization for participants in the maintenance group; 365 days after Treg infusion for the participants in the polyTregs or darTregs groups
Population: Intent-to-treat population who initiated study treatment, subset to those with culture-proven and clinically diagnosed infections
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maintenance | Timing of Culture-proven and Clinically Diagnosed Infection | 179.0 Days |
| polyTregs | Timing of Culture-proven and Clinically Diagnosed Infection | 179.0 Days |
| darTregs | Timing of Culture-proven and Clinically Diagnosed Infection | 84.0 Days |
Secondary
Timing of polyTregs Infusion Reactions
An infusion reaction is characterized by an adverse reaction to the infusion of pharmacological substance, as defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 set forth by the National Cancer Institute.
Time frame: 365 days after Treg infusion for the participants in the polyTregs group
Population: Intent-to-treat population, subset to participants who received the polyTregs infusion and had a polyTregs infusion reaction. No participants met the criteria for inclusion in this analysis population.