Delayed Infusion of DCreg in Living Donor Liver Transplantation

NCT04208919 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY20010215
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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 who are between 1 and 3 years after transplantation and meet specific criteria (no positive crossmatch, no clinically treated rejection within 2 years preceding enrollment, permissive liver function tests (LFTs) within 30 days preceding enrollment, no prior liver biopsy showing significant fibrosis or ductopenia\*) will be enrolled and will undergo a protocol liver biopsy unless they have had a permissive liver biopsy\*\* within 90 days of anticipated immunosuppression weaning. Those patients with permissive liver biopsy\*\* will then receive a single infusion of donor-derived DCreg and will remain on their current standard of care (SOC) immunosuppression. One week after DCreg infusion, immunosuppression weaning will be initiated. Recipients will be slowly weaned off immunosuppression. 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 will undergo a liver biopsy at the end of the study. \* Permissive LFTs are defined as ALT, AST and total bilirubin \< 2.5 times the upper limit of normal. \*\*A permissive biopsy is based on 2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology (the criteria detailed in Table 8, Demetris et al. 2016).

Conditions

Living Donor Liver Transplantation

Keywords

Regulatory Dendritic Cells

Outcome Measures

Primary Outcomes (9)

• The proportion of recipients who experience CTCAE Grade 4 or higher infusion reaction

  Safety will be determined by assessing the proportion of subjects who experience CTCAE Grade 4 or higher infusion reaction

  1 day

• The proportion of recipients who experience CTCAE Grade 4 or higher infection

  Safety will be determined by assessing the proportion of subjects who experience CTCAE Grade 4 or higher infection

  4 years

• The proportion of recipients who experience experience malignancy other than non-melanoma skin cancer or HCC recurrence

  Safety will be determined by assessing the proportion of subjects who experience malignancy other than non-melanoma skin cancer or HCC recurrence

  4 years

• The proportion of recipients who experience rejection resulting in recipient death or retransplantation

  Safety will be determined by assessing the proportion of subjects who experience rejection resulting in recipient death or retransplantation

  4 years

• The proportion of recipients who experience biopsy-proven severe acute rejection

  Safety will be determined by assessing the proportion of subjects who experience biopsy-proven severe acute rejection

  4 years

• The proportion of recipients who experience any grade chronic rejection

  Safety will be determined by assessing the proportion of subjects who experience any grade chronic rejection

  4 years

• The proportion of recipients who experience non-surgical graft loss

  Safety will be determined by assessing the proportion of subjects who experience non-surgical graft loss

  4 years

• The proportion of recipients who die

  Safety will be determined by assessing the proportion of subjects who die

  4 years

• Preliminary Efficacy of using DCreg therapy to facilitate immunosuppression weaning

  Proportion of patients able to achieve immunosuppression withdrawal with operational tolerance 1 year after complete immunosuppression cessation based on specific liver biopsy criteria

  2 years

Secondary Outcomes (4)

• Donor Specific Antigen (DSA) levels

  4 years

• Change in renal function

  Change from baseline to 36 months post-weaning

• Change in Quality of Life as measured by the Short Form 36 (SF-36)

  Change from baseline to 36 months post-weaning

• Change in cardiovascular risk factors

  Change from baseline to 36 months post-weaning

Study Arms (1)

DCreg Prior to Weaning

EXPERIMENTAL

Regulatory dendritic cells that were derived from the recipient's liver donor will be infused into the recipient one week prior to the initiation of immunosuppression weaning.

Biological: Donor-derived DCreg

Interventions

Donor-derived DCreg BIOLOGICAL

Regulatory dendritic cells that were prepared from a donor leukapheresis will be infused into liver transplant recipients 7 days prior to the start of immunosuppression weaning.

DCreg Prior to Weaning

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Donor
• Able to understand and provide informed consent
• Male or female age 18 or older at the time of enrollment
• Have no contraindication to leukapheresis
• For females of childbearing potential, a negative urine or serum pregnancy test
• No live vaccines within 12 weeks prior to leukapheresis
• Negative health history for risk factors related to Creutzfeldt-Jakob disease
• Negative for West Nile Virus(a)
• Negative for HIV (5th generation Test and NAT), HTLV-1, HTLV-2;(a)
• Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and NAT)(a)
• does not preclude donors from undergoing leukapheresis but cells may not be infused into recipient.
• Recipients

You may not qualify if:

• Age 18 or older at the time of enrollment
• Underwent de novo (first) liver transplant 1 to 3 years prior to enrollment
• Female subjects of childbearing potential must have a negative pregnancy test upon study entry.
• 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.
• Recipients
• History of positive crossmatch (performed prior to transplant)
• Clinically treated rejection episode within 2 years prior to enrollment
• Non-permissive LFTs within past 1 month
• Repeat liver transplant
• Prior other solid organ transplant
• Significant co-morbid conditions such as severe heart or lung disease
• Following etiology of liver disease: Primary Sclerosing Cholangitis (PSC), autoimmune, Primary Biliary Cirrhosis (PBC)
• If prior history of Hepatitis B or C (HBV or HCV) infection, Hepatitis B or C Virus (HBV or HCV) viral load positive at the time of enrollment (successfully treated HBV or HCV patients are not excluded)
• Positive antigen-antibody immunoassay for HIV-1/2
• Any prior biopsy showing significant fibrosis or ductopenia.

Sponsors & Collaborators

• Angus W. Thomson PhD DSc: lead

Study Sites (1)

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Study Officials

• Abhinav Humar

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: December 23, 2019
• Study Start: December 18, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)