Trial Outcomes & Findings for Liver Transplantation With Tregs at UCSF (NCT NCT03654040)

Last Updated: 2024-04-23

Results Overview

* AEs will be attributed to alloantigen-reactive Tregs (arTreg) when the AE is reported with possible or related attribution to arTreg. * Grading: According to the NCI Common Terminology Criteria for Adverse Events Manual \[NCI-CTCAE version 5.0, published November 27, 2017\].

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

42 participants

Primary outcome timeframe

From arTreg infusion through completion of study participation

Results posted on

2024-04-23

Participant Flow

30 prospective transplant recipients and 12 living donors were enrolled from a single study center in the US between April 2021 and February 2023. The study was terminated by the sponsor in February 2023 prior to any participant receiving the investigational product, arTregs.

Participants were enrolled prior to transplant \& had to wait for an available liver which was received per the institution's standard of care. If recipient rec'd a liver from a living donor, the donor also enrolled into the study to collect biological samples to aid in the manufacturing of the investigation product, arTregs. Immunosuppression medication was required to be stabilized and converted from tacrolimus to everolimus prior to transplant recipient receiving the investigational product

Participant milestones

Participant milestones
Measure	Enrolled Transplant Recipient, Did Not Receive arTregs These participants were prospective transplant recipients who were consented and enrolled into the study, but did not receive arTregs.	Enrolled Living Donor These participants were living donors of the prospective transplant recipient who consented and enrolled into the study.
Overall Study STARTED	30	12
Overall Study COMPLETED	0	5
Overall Study NOT COMPLETED	30	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Enrolled Transplant Recipient, Did Not Receive arTregs These participants were prospective transplant recipients who were consented and enrolled into the study, but did not receive arTregs.	Enrolled Living Donor These participants were living donors of the prospective transplant recipient who consented and enrolled into the study.
Overall Study Death	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Study terminated by sponsor	8	2
Overall Study Failure to initiate study therapy	2	0
Overall Study Transplanted at another center	2	0
Overall Study Failure to meet eligibility criteria	14	2
Overall Study No longer transplant candidate	1	0
Overall Study Manufacturing unable to accept specimens	1	0
Overall Study Recipient ineligible	0	2
Overall Study Received deceased liver	0	1

Baseline Characteristics

Liver Transplantation With Tregs at UCSF

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enrolled, Transplant Recipient Did Not Receive arTregs n=30 Participants These participants were consented and enrolled into the study but did not receive arTregs.	Enrolled Living Donor n=12 Participants These participants were living donors of the prospective transplant recipient who consented and enrolled into the study.	Total n=42 Participants Total of all reporting groups
Age, Continuous	54.6 years STANDARD_DEVIATION 10.35 • n=5 Participants	37.3 years STANDARD_DEVIATION 14.09 • n=7 Participants	49.9 years STANDARD_DEVIATION 13.69 • n=5 Participants
Age, Customized Age, Categorical · <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Customized Age, Categorical · Between 18 and 65 years	26 Participants n=5 Participants	11 Participants n=7 Participants	37 Participants n=5 Participants
Age, Customized Age, Categorical · >=65 years	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Age, Customized Age, Categorical · Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex/Gender, Customized Female	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Sex/Gender, Customized Male	18 Participants n=5 Participants	5 Participants n=7 Participants	23 Participants n=5 Participants
Sex/Gender, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	8 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 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
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	9 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	12 participants n=7 Participants	42 participants n=5 Participants

PRIMARY outcome

Timeframe: From arTreg infusion through completion of study participation

Population: Data were not collected. The study was terminated prior to any participant receiving the investigational product, arTregs. The study's low enrollment would not allow for study completion within the necessary timeframe.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: From ≤3 days prior to arTreg infusion through completion of study participation (Up to 3 months)

Population: These participants were consented and enrolled into the study and received at least part of the supportive regimen of leukapheresis, cyclophosphamide, or mesna.

* AEs will be attributed to the supportive regimen for this study when the AE is reported with possible or related attribution to leukapheresis, cyclophosphamide, or mesna. * Grading: According to the NCI Common Terminology Criteria for Adverse Events Manual \[NCI-CTCAE version 5.0, published November 27, 2017\].

Outcome measures

Outcome measures
Measure	Enrolled, Received arTregs n=1 Participants These participants were consented and enrolled into the study and received arTregs.
Number and Severity of Adverse Events (AEs) Attributed to Supportive Regimen: Leukapheresis, Cyclophosphamide or Mesna	0 Participants

PRIMARY outcome

Timeframe: 52 (± 4 weeks) after the last dose of immunosuppression

Operational tolerance is defined as: * Discontinuation of all immunosuppression (IS) for 52 weeks, * Alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) ≤ 50 U/L for ≥ 2 measurements separated by ≥1 week in the 6 weeks prior to the liver biopsy at 52 weeks after the last IS dose, and * Liver biopsy at 52 weeks (±4 weeks) after the last IS dose that meets the biopsy criteria for operational tolerance, as assessed by central pathology.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time of enrollment through completion of study participation (Up to 1.8 years)

Population: Participants who enrolled, but did not receive arTregs

The number of participants that are diagnosed with malignancy, any type.

Outcome measures

Outcome measures
Measure	Enrolled, Received arTregs n=30 Participants These participants were consented and enrolled into the study and received arTregs.
Number of Participants Who Develop a Malignancy	1 participants

Adverse Events

Enrolled Transplant Recipient, Did Not Receive arTregs

Serious events: 3 serious events

Other events: 3 other events

Deaths: 1 deaths

Enrolled Living Donor

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Enrolled Transplant Recipient, Did Not Receive arTregs n=30 participants at risk These participants were consented and enrolled into the study, but did not receive arTregs.	Enrolled Living Donor n=12 participants at risk These participants were living donors of the prospective transplant recipient who consented and enrolled into the study.
Hepatobiliary disorders Cholangitis	3.3% 1/30 • Number of events 1 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.	0.00% 0/12 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.
Infections and infestations COVID-19	6.7% 2/30 • Number of events 2 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.	0.00% 0/12 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.

Other adverse events

Other adverse events
Measure	Enrolled Transplant Recipient, Did Not Receive arTregs n=30 participants at risk These participants were consented and enrolled into the study, but did not receive arTregs.	Enrolled Living Donor n=12 participants at risk These participants were living donors of the prospective transplant recipient who consented and enrolled into the study.
Blood and lymphatic system disorders Neutropenia	3.3% 1/30 • Number of events 1 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.	0.00% 0/12 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.
Gastrointestinal disorders Stomatitis	3.3% 1/30 • Number of events 1 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.	0.00% 0/12 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.
Hepatobiliary disorders Bile duct stenosis	3.3% 1/30 • Number of events 1 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.	0.00% 0/12 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	3.3% 1/30 • Number of events 1 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.	0.00% 0/12 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.
General disorders Oedema peripheral	3.3% 1/30 • Number of events 1 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.	0.00% 0/12 • Up to 1.8 years Prior to study stage 2, only confirmed cases of COVID-19 were collected. All AEs were collected from the time of informed consent obtain during study stage 2 until the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place