DCreg in Living Donor Liver Transplantation

Phase 1

Active, not recruiting

• Conditions: Living Donor Liver Transplantation

• Registration Number: NCT03164265
• Lead Sponsor: Angus W. Thomson PhD DSc

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.

Study Timeline

• Study First Submitted: 2017-05-10
• Study First Submitted QC: 2017-05-19
• Study First Posted: 2017-05-23
• Study Start: 2017-08-30
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-11
• Last Update Posted: 2023-09-13
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 16

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 65 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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Proportion of Safety Events	6 years	1. Safety: Safety will be determined by assessing the proportion 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 Outcome Measures

Name	Time	Method
Change in renal function	1 year post-transplantation (prior to weaning) 4.5 years post transplantation	Change in renal function
Donor Specific Antigen (DSA) levels	6 years	DSA levels early (\<6 weeks) and late (\> 6 weeks) after transplantation
Change in Quality of Life	1 year post-transplantation (prior to weaning) 4.5 years post transplantation	Change in Quality of Life as measured by the Short Form 36 (SF-36) Quality of Life questionnaire
Change in cardiovascular risk factors	1 year post-transplantation (prior to weaning) 4.5 years post transplantation	Change in cardiovascular risk factors including incidence of hypertension necessitating medication, post-transplant diabetes, hyperlipidemia, hypercholesterolemia

Trial Locations

Locations (1)

UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States