DCreg in Living Donor Liver Transplantation

Safety and Preliminary Efficacy of Donor-derived Regulatory Dendritic Cell (DCreg) Infusion and Immunosuppression Withdrawal in Living Donor Liver Transplantation

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03164265

Enrollment

Registered

2017-05-23

Start date

2017-08-30

Completion date

2024-07-15

Last updated

2025-09-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Living Donor Liver Transplantation

Keywords

Regulatory Dendritic Cells

Brief summary

Phase I/II, single center, prospective, open-label, non-controlled, non-randomized, interventional, cohort study in which low risk living donor liver transplant (LDLT) recipients will receive a single infusion of donor-derived DCreg 1 week prior to transplantation. All patients will be maintained on MPA and Tacrolimus (Tac) for the 1st 6 months after transplantation. At that time point, recipients meeting specific criteria will be slowly weaned off MPA per standard of care over a period of 6 months. Participants will then be evaluated for TAC weaning at 1 yr after transplantation. Those who meet specific criteria be weaned off Tac over 6 months . Successfully weaned participants who remain rejection-free will undergo 3 years of follow-up after the last dose of immunosuppression.

Detailed description

Phase I/II, single center, prospective, open-label, non-controlled, non-randomized, interventional, cohort study in which low risk living donor liver transplant (LDLT) recipients will receive a single infusion of donor-derived DCreg with concurrent mycophenolic acid (MPA) therapy (1/2 dose) 1 week prior to transplantation. All patients will be maintained on MPA and Tacrolimus (Tac) for the 1st 6 months after transplantation. At that time point, recipients meeting specific criteria (no rejection and permissive liver function tests (LFTs)) will be slowly weaned off MPA per standard of care over a period of 6 months. Participants will then be evaluated for TAC weaning at 1 yr after transplantation. Those who meet the criteria of no rejection and permissive LFTs will undergo a protocol liver biopsy and proceed to Tac weaning over 6 months if liver biopsy is permissive. Successfully weaned participants who remain rejection-free will undergo 3 years of follow-up after the last dose of immunosuppression. They will undergo a liver biopsy at 1 yr and 3 yrs after immunosuppression withdrawal. Participants who are removed from the study protocol at any time will return to standard of care but will continue to be followed by the study team and may undergo a liver biopsy at the end of the study (4.5 yrs after transplantation). For subjects who return to standard of care (on immunosuppression at end of study), the year 4.5 biopsy will be optional.

Interventions

BIOLOGICALRegulatory Donor-Derived Dendritic Cell infusion

Regulatory dendritic cells that were prepared from a donor leukapheresis will be infused into liver transplant recipients 7 days prior to surgery

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

Donors 1. Able to understand and provide informed consent; 2. Male or female between the ages of 18-55; 3. Meet all standard institutional and UNOS criteria for liver donation; 4. For females of childbearing potential, a negative urine or serum pregnancy test; 5. Negative for HIV (5th generation Test and NAT), HTLV-1, HTLV-2;(\*) 6. Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and NAT)(\*) Recipients 1. Low risk recipient approved for LDLT, irrespective of gender, race, or ethnic background. Low risk is defined by absence of

Exclusion criteria

(below). 2. Between ages 18 and 75 years 3. Undergoing de novo (first) liver transplant 4. Female subjects of childbearing potential must have a negative pregnancy test upon study entry. 5. Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used from the time that study treatment begins until 1 year after completion of immunosuppression withdrawal. (\*)does not preclude donors from undergoing leukapheresis but cells may not be infused into recipient.

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Safety Events	6 years	1\. Safety: Safety will be determined by assessing the percentage of subjects experiencing the following events: i) CTCAE Grade 4 or higher infusion reaction; ii) CTCAE Grade 4 or higher infection; iii) Malignancy other than non-melanoma skin cancer or HCC recurrence; iv) Rejection resulting in recipient death or retransplantation; v) Biopsy-proven severe acute rejection; vi) Any grade chronic rejection; vii) Non-surgical graft loss; viii) Recipient death;
Preliminary Efficacy	2.5 years	Proportion of patients able to achieve staged immunosuppression withdrawal with operational tolerance

Secondary

Measure	Time frame	Description
Donor Specific Antigen (DSA) Levels	6 years	DSA levels early (\<6 weeks) and late (\> 6 weeks) after transplantation
Change in Renal Function	from baseline to 4.5 years post transplantation	Change in renal function measured by change in estimated glomerular filtration rate (eGFR)
Change in Quality of Life	1 year post-transplantation (prior to weaning) 4.5 years post transplantation	Scale title: Short Form 36 (SF-36) Quality of Life questionnaire. Minimum and maximum values 0 to 100 higher scores indicates better health.
Change in Cardiovascular Risk Factors (Systolic Blood Pressure)	from baseline to 4.5 years post transplantation	—
Change in Cardiovascular Risk Factors (Triglycerides)	from baseline to 4.5 years	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
Study Group Prospectively enrolled living donor liver transplant recipients pre-op.	13
Total	13

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Physician Decision	3

Baseline characteristics

Characteristic	Study Group
Age, Continuous	62 years STANDARD_DEVIATION 7
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	12 Participants
Region of Enrollment United States	13 Participants
Sex: Female, Male Female	8 Participants
Sex: Female, Male Male	5 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 13
other Total, other adverse events	5 / 13
serious Total, serious adverse events	0 / 13

Outcome results

Primary

Preliminary Efficacy

Proportion of patients able to achieve staged immunosuppression withdrawal with operational tolerance

Time frame: 2.5 years