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

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.

Study Overview

• Status: Completed
• Conditions: Living Donor Liver Transplantation
• Intervention / Treatment: Biological: Regulatory Donor-Derived Dendritic Cell infusion

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study arm; Living donor liver transplant recipients receiving donor-derived DCreg infusion. This is a single arm study	Biological: Regulatory 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; Other Names: DCreg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary Efficacy	Proportion of patients able to achieve staged immunosuppression withdrawal with operational tolerance	2.5 years
Proportion of Safety Events	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;	6 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Angus W. Thomson PhD DSc
• Collaborators: University of Pittsburgh
• Investigators: Principal Investigator: Abhinav Humar, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2017
• Primary Completion (Actual): July 15, 2024
• Study Completion (Actual): July 15, 2024

Study Registration Dates

• First Submitted: May 10, 2017
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (Actual): May 23, 2017

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Regulatory Dendritic Cells
• Other Study ID Numbers: STUDY19020267; IND#17271 (Other Identifier: FDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No