Trial Outcomes & Findings for Treg Therapy in Subclinical Inflammation in Kidney Transplantation (NCT NCT02711826)

NCT ID: NCT02711826

Last Updated: 2025-04-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

32 participants

Primary outcome timeframe

405 days post-group allocation

Results posted on

2025-04-09

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure
Maintenance
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
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.
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.
Enrolled, Discontinued Pre-Randomization
Participants who failed screening or were eligible but did not proceed to randomization.
Enrolled, Living Donor
Living donors of the prospective transplant recipient were consented and enrolled into the study.
Overall Study
STARTED
3
9
6
9
5
Overall Study
COMPLETED
3
7
1
0
5
Overall Study
NOT COMPLETED
0
2
5
9
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Maintenance
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
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.
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.
Enrolled, Discontinued Pre-Randomization
Participants who failed screening or were eligible but did not proceed to randomization.
Enrolled, Living Donor
Living donors of the prospective transplant recipient were consented and enrolled into the study.
Overall Study
Physician Decision
0
0
0
1
0
Overall Study
Withdrawal by Subject
0
1
0
4
0
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
Screen failures
0
0
0
4
0

Baseline Characteristics

Treg Therapy in Subclinical Inflammation in Kidney Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Maintenance
n=8 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
darTregs
n=1 Participants
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.
Enrolled, Living Donor
n=5 Participants
Living donors of the prospective transplant recipient were consented and enrolled into the study.
Total
n=21 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Age, Categorical
Between 18 and 65 years
7 Participants
n=5 Participants
6 Participants
n=7 Participants
1 Participants
n=5 Participants
4 Participants
n=4 Participants
18 Participants
n=21 Participants
Age, Categorical
>=65 years
1 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
3 Participants
n=21 Participants
Age, Continuous
47.5 years
STANDARD_DEVIATION 11.78 • n=5 Participants
52.1 years
STANDARD_DEVIATION 11.94 • n=7 Participants
58.0 years
STANDARD_DEVIATION 0.00 • n=5 Participants
48.0 years
STANDARD_DEVIATION 17.66 • n=4 Participants
49.7 years
STANDARD_DEVIATION 12.73 • n=21 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
4 Participants
n=7 Participants
0 Participants
n=5 Participants
3 Participants
n=4 Participants
11 Participants
n=21 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
3 Participants
n=7 Participants
1 Participants
n=5 Participants
2 Participants
n=4 Participants
10 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
n=5 Participants
3 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
6 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants
n=5 Participants
4 Participants
n=7 Participants
1 Participants
n=5 Participants
4 Participants
n=4 Participants
15 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=5 Participants
2 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
4 Participants
n=21 Participants
Race (NIH/OMB)
White
5 Participants
n=5 Participants
2 Participants
n=7 Participants
1 Participants
n=5 Participants
2 Participants
n=4 Participants
10 Participants
n=21 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
n=5 Participants
3 Participants
n=7 Participants
0 Participants
n=5 Participants
2 Participants
n=4 Participants
7 Participants
n=21 Participants
Region of Enrollment
United States
8 participants
n=5 Participants
7 participants
n=7 Participants
1 participants
n=5 Participants
5 participants
n=4 Participants
21 participants
n=21 Participants

PRIMARY outcome

Timeframe: 405 days post-group allocation

Population: Intent-to-treat population who initiated study treatment, subset to participants with available central pathology read data.

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=6 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
darTregs
n=1 Participants
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.
Incidence of Banff 2A or Higher Acute Cell-mediated Rejection and/or Acute Antibody Mediated Rejection
0 Participants
0 Participants
0 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=8 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
darTregs
n=1 Participants
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.
Incidence of Study Defined Grade 3 or Higher Infection
2 Participants
3 Participants
1 Participants

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=2 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=3 Participants
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.
darTregs
n=1 Participants
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.
Timing of Study Defined Grade 3 or Higher Infection
179.0 Days
Interval 99.0 to 259.0
116.0 Days
Interval 36.0 to 179.0
84.0 Days
Interval 84.0 to 84.0

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=4 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=6 Participants
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.
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.
Percent Change in Inflammation
-59.16 Percent change
Interval -70.65 to -35.35
-78.95 Percent change
Interval -85.41 to -68.11

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
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.
Incidence of polyTregs Infusion Reactions
0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=8 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
darTregs
n=1 Participants
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.
Incidence of Culture-proven and Clinically Diagnosed Infection.
2 Participants
3 Participants
1 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=2 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=3 Participants
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.
darTregs
n=1 Participants
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.
Severity of Culture-proven and Clinically Diagnosed Infection
Grade 3
2 Participants
2 Participants
1 Participants
Severity of Culture-proven and Clinically Diagnosed Infection
No Grade
0 Participants
1 Participants
0 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=2 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=3 Participants
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.
darTregs
n=1 Participants
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.
Timing of Culture-proven and Clinically Diagnosed Infection
179.0 Days
Interval 99.0 to 259.0
179.0 Days
Interval 36.0 to 215.0
84.0 Days
Interval 84.0 to 84.0

SECONDARY outcome

Timeframe: 405 days post-group allocation

Population: Intent-to-treat population who initiated study treatment, subset to participants with available central pathology read data.

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=6 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
darTregs
n=1 Participants
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.
Incidence of Acute Rejection Using Banff Grading
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 405 days post-group allocation

Population: Intent-to-treat population who initiated study treatment

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=8 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
darTregs
n=1 Participants
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.
Incidence of BK Viremia
0 Participants
1 Participants
0 Participants

SECONDARY outcome

Timeframe: 405 days post-group allocation

Population: Intent-to-treat population who initiated treatment, subset to participants who experienced 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.

Outcome measures

Outcome measures
Measure
Maintenance
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=1 Participants
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.
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.
Timing of BK Viremia
365.00 Days
Interval 365.0 to 365.0

SECONDARY outcome

Timeframe: 405 days post-group allocation

Population: Intent-to-treat population who initiated treatment

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=8 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
darTregs
n=1 Participants
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.
Incidence of Cytomegalovirus (CMV) Reactivation
0 Participants
0 Participants
1 Participants

SECONDARY outcome

Timeframe: 405 days post-group allocation

Population: Intent-to-treat population who initiated treatment, subset to participants who experienced 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.

Outcome measures

Outcome measures
Measure
Maintenance
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
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.
darTregs
n=1 Participants
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.
Timing of CMV Reactivation
84.0 Days
Interval 84.0 to 84.0

SECONDARY outcome

Timeframe: 405 days post-group allocation

Population: Intent-to-treat population who initiated treatment

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=8 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=7 Participants
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.
darTregs
n=1 Participants
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.
Incidence of > 10% Decrease in Estimated Glomerular Filtration Rate (eGFR) Compared to Baseline
5 Participants
6 Participants
1 Participants

SECONDARY outcome

Timeframe: 405 days post-group allocation

Population: Intent-to-treat population who initiated treatment, subset to participants who had a \>10% decrease in eGFR.

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=5 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=6 Participants
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.
darTregs
n=1 Participants
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.
Timing of > 10% Decrease in eGFR Compared to Baseline
51.0 Days
Interval 37.0 to 60.0
53.0 Days
Interval 30.0 to 64.0
44.0 Days
Interval 44.0 to 44.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=6 Participants
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.
darTregs
n=1 Participants
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.
Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy
0 Participants
2 Participants
0 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=6 Participants
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.
darTregs
n=1 Participants
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.
Proportion of Participants Exhibiting >=50% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the Week 2 Kidney Biopsy
0 Participants
1 Participants
0 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
Maintenance
n=4 Participants
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=6 Participants
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.
darTregs
n=1 Participants
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.
Proportion of Participants Exhibiting >=25% Relative Decrease of Inflammation Between Baseline Kidney Biopsy and the 6 Month Kidney Biopsy
3 Participants
5 Participants
1 Participants

Adverse Events

Maintenance

Serious events: 3 serious events
Other events: 2 other events
Deaths: 0 deaths

polyTregs

Serious events: 4 serious events
Other events: 4 other events
Deaths: 0 deaths

darTregs

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Enrolled, Living Donor

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Maintenance
n=8 participants at risk
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=8 participants at risk
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.
darTregs
n=2 participants at risk
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.
Enrolled, Living Donor
n=5 participants at risk
Living donors of the prospective transplant recipient were consented and enrolled into the study.
Gastrointestinal disorders
Colitis
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
General disorders
Pyrexia
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Immune system disorders
Transplant rejection
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
50.0%
1/2 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Infections and infestations
Corona virus infection
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Infections and infestations
Cytomegalovirus infection
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
50.0%
1/2 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Infections and infestations
Gastroenteritis
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Infections and infestations
Pyelonephritis
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Infections and infestations
Upper respiratory tract infection
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Infections and infestations
Urinary tract infection
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Metabolism and nutrition disorders
Hyperglycaemia
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.

Other adverse events

Other adverse events
Measure
Maintenance
n=8 participants at risk
Participants in this group continued standard CNI-based maintenance immunosuppression therapy with no intervention.
polyTregs
n=8 participants at risk
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.
darTregs
n=2 participants at risk
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.
Enrolled, Living Donor
n=5 participants at risk
Living donors of the prospective transplant recipient were consented and enrolled into the study.
Gastrointestinal disorders
Diarrhoea
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Gastrointestinal disorders
Nausea
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Infections and infestations
Urinary tract infection
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Injury, poisoning and procedural complications
Contusion
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Injury, poisoning and procedural complications
Foot fracture
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Metabolism and nutrition disorders
Gout
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Metabolism and nutrition disorders
Hypercalcaemia
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Psychiatric disorders
Major depression
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Respiratory, thoracic and mediastinal disorders
Haemoptysis
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Skin and subcutaneous tissue disorders
Swelling face
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Vascular disorders
Hypertension
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
Vascular disorders
Thrombophlebitis superficial
12.5%
1/8 • Number of events 1 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/8 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/2 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.
0.00%
0/5 • Adverse events were collected from the time of first study mandated procedure until a subject completes study participation (405 days after randomization for participants in the maintenance group; 365 days after treg infusion for the participants in the polyTregs or darTregs groups) or until 30 days after they prematurely withdraw (without withdrawing consent) or is withdrawn from the study.

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place