DCreg in Living Donor Liver Transplantation

Angus W. Thomson PhD DSc16 enrolled

Overview

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.

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

Allocation

Purpose

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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;

Time frame: 6 years

Preliminary Efficacy

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

Time frame: 2.5 years

Secondary Outcomes

Donor Specific Antigen (DSA) Levels

DSA levels early (\<6 weeks) and late (\> 6 weeks) after transplantation

Time frame: 6 years

Change in Renal Function

Change in renal function measured by change in estimated glomerular filtration rate (eGFR)

Time frame: 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.

Time frame: 1 year post-transplantation (prior to weaning) 4.5 years post transplantation

Change in Cardiovascular Risk Factors (Systolic Blood Pressure)

Time frame: from baseline to 4.5 years post transplantation

Change in Cardiovascular Risk Factors (Triglycerides)

Time frame: from baseline to 4.5 years

DCreg in Living Donor Liver Transplantation

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes