Hepatitis C Positive Donor Into Hepatitis C Negative Recipients

NCT03702218 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: HP-00083009
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Despite many efforts to increase the size of the donor pool, there is a large and growing disparity between the number of donor kidneys and livers available for transplantation and the number of patients on the transplant waiting list. New donor pools are needed to satisfy the lack of available donor organs, along with expanded criteria for the existing donor pools. A new standard of care now exists at most local and regional transplant centers. This new standard of care is based on the use of multiple direct-acting antiviral agents (DAAs) for treatment of hepatitis C virus (HCV) that have been approved by the Food and Drug Administration (FDA) for the treatment of hepatitis C and are associated with high HCV cure rates and minimal side effect profiles. The efficacy and tolerability of these medications has allowed the expansion of the available donor pool by making HCV antibody positive non viremic organs and HCV-viremic organs (when HCV is detectable in the blood) available to HCV-naive recipients on the organ transplantation waiting list. Expansion of this donor pool may decrease time on the waiting list and improve quality of life and survival while waiting for organ transplantation. Study Aim: We propose a clinical protocol to utilize solid organs from exposed and/or HCV-viremic organ donors for transplantation into HCV negative recipients. The primary purpose of the clinical protocol is to: Collect prospective standard of care laboratory data on the results of these interventions

Conditions

Hepatitis C

Keywords

Transplantation; Hepatitis C

Outcome Measures

Primary Outcomes (1)

• SVR after receiving an organ from a donor previously exposed to Hepatitis C after treatment direct-acting antiviral drugs.

  To improve access to transplantation with use of HCV-non viremic and HCV-viremic organs in HCV negative patients

  12 months

Study Arms (3)

Hep C Ab + NAT - Donor to Naïve Recipient

EXPERIMENTAL

HCV Ab and HCV NAT testing at 3 days, week 1, week 2 and monthly for 3 months, at 6 months and 1 year. In approximately 16% of the patients, active hepatis C infection will ensue. For these patients, treatment is as follows. Liver Transplant: • Combinations of choice: * Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6 * Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR\>30 * Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR\>30 Kidney Transplant: • Combinations of choice: * Mavyret (glecaprevir/pibrentasvir) - genotype 1-6 * Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR\>30

Drug: Direct Acting Antivirals

Hep C Ab+ NAT+ Donor to Naïve Recipient

EXPERIMENTAL

HCV RNA levels, liver biochemistries, and renal function will be measured 3 days after transplant. HCV Genotype will be determined after HCV RNA is \>1,000 IU/mL. HCV RNA levels will be measured weekly after transplant until HCV treatment is initiated. Liver Transplant: • Combinations of choice: * Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6 * Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR\>30 * Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR\>30 Kidney Transplant: • Combinations of choice: * Mavyret (glecaprevir/pibrentasvir) - genotype 1-6 * Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR\>30

Drug: Direct Acting Antivirals

Hep C Ab- NAT - Donor to Naïve Recipient

ACTIVE COMPARATOR

Current standard of care for donor recipient infectious disease matching. No treatment necessary

Drug: Direct Acting Antivirals

Interventions

Direct Acting Antivirals DRUG

Patients who are given organ transplants from donors that are Ab positive and NAT negative or Ab positive and NAT positive for Hepatitis C will be treated with direct acting antivirals after transplant if they become NAT+ for hepatitis C. Interventions as follows. Liver Transplant: • Combinations of choice: * Mavyret (glecaprevir/pibrentasvir) - Genotype 1-6 * Harvoni (ledipasvir/sofosbuvir) + Ribavirin - Genotypes 1, 4, 5, 6; GFR\>30 * Epclusa (sofosbuvir/velpatasvir) + Ribavirin - Genotypes 1-6; GFR\>30 Kidney Transplant: • Combinations of choice: * Mavyret (glecaprevir/pibrentasvir) - genotype 1-6 * Harvoni (sofosbuvir/ledipasvir) - genotype 1, 4; GFR\>30

Hep C Ab + NAT - Donor to Naïve Recipient; Hep C Ab+ NAT+ Donor to Naïve Recipient; Hep C Ab- NAT - Donor to Naïve Recipient

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing solid organ transplantation, including liver, kidney, and simultaneous liver-kidney who are not chronically infected with HCV
• No evident contraindication for organ transplantation
• HCV RNA negative (can be isolated HCV antibody positive provided the patient will have no history of previously treated HCV)
• Age 18-75 years at the time of transplantation
• Signed Informed Consent Form
• No identified living organ donor
• Able to travel to the University of Maryland for routine post-transplant and HCV follow-up visits
• Men and women must agree to use at least one barrier method to prevent any secretion exchange
• No active illicit drug use
• Qualitative HCV nucleic acid test (NAT) positive and/or Hepatitis C antibody positive HCV donors offered to the University of Maryland.

You may not qualify if:

• History of prior solid organ transplantation
• HIV infection
• HBV surface antigen or DNA positive. Organs from HCV positive donors who are also Hepatitis B core antibody positive (hepatitis B surface antigen negative) can be used. These patients will however need to undergo prophylaxis for HBV according to their respective organ specific criteria and during treatment for hepatitis C due to the increased risk of reactivation of hepatitis B with DAA therapy
• Waitlisted for a multi-organ transplant (with the exception of simultaneous liver-kidney transplant)
• HCV RNA positive (can be isolated HCV antibody positive provided the patient will have no history of previously treated HCV)
• Prior direct-acting antiviral (DAA) treatment for HCV. Patients previously treated with interferon-based regimens may be included.
• Every donor that is considered unsuitable by the transplant surgeon for any reason.
• Hepatocellular carcinoma
• HIV infection
• Use of HCV positive livers to be determined according to current existing criteria

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (2)

• Goldberg DS, Blumberg E, McCauley M, Abt P, Levine M. Improving Organ Utilization to Help Overcome the Tragedies of the Opioid Epidemic. Am J Transplant. 2016 Oct;16(10):2836-2841. doi: 10.1111/ajt.13971. Epub 2016 Aug 24.

  PMID: 27438538 BACKGROUND

• Bari K, Luckett K, Kaiser T, Diwan T, Cuffy M, Schoech MR, Safdar K, Blackard JT, Apewokin S, Paterno F, Sherman KE, Zucker SD, Anwar N, Shah SA. Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients. Hepatology. 2018 May;67(5):1673-1682. doi: 10.1002/hep.29704. Epub 2018 Mar 26.

  PMID: 29205441 BACKGROUND

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 11, 2018
• Study Start: July 1, 2019
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: May 6, 2023

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP

Locations

US (1)