Pan-genotypic Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Lung Transplant

This is a proof of concept, single center study for the donation of HCV-positive lungs to HCV negative recipient patients, with preemptive, interventional treatment with 8 weeks of commercially available DAA therapy to prevent HCV transmission upon transplantation.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C; Respiratory Failure
• Intervention / Treatment: Drug: Clinically prescribed direct acting antiviral (Mavyret or Epclusa) HCV treatment for 8 weeks

Detailed Description

The goal of this study is to determine if preoperative dosing and sustained administration of pan-genotypic DAA therapy after lungs transplantation prevents the transmission of hepatitis C virus (HCV) infection from an HCVpositive donor lung to an HCV naïve recipient.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Met MGH transplant center criteria, listed for lung transplant
• Able to sign informed consent

Exclusion Criteria:

• Pregnant or nursing (lactating) women
• HIV positivity
• Any contra-indication to lung transplantation per center protocol
• For study patients in whom Epclusa® therapy is being considered, exclusion criteria includes patients on the following p-glycoprotein inducers or moderate to potent CYP inducers that cannot stop therapy: carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, rifapentine, St. John's wort.
• For study patients in whom MavyretTM therapy is being considered, exclusion criteria includes patients on the following medications who cannot stop therapy: carbamazepine, rifampin, St. John's wort, and ethinyl estradiol-containing oral contraceptives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Treatment with Direct Acting Antiviral for HCV; 8 weeks of treatment with HCV Direct Acting Antiviral tablet (Mavyret or Epclusa)	Drug: Clinically prescribed direct acting antiviral (Mavyret or Epclusa) HCV treatment for 8 weeks; 8 weeks of direct acting antiviral treatment based on clinical indication (either Mavyret or Epclusa); Other Names: Epclusa; Mavyret; DAA treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Undetectable Blood HCV RNA Level	Negative HCV RNA by blood testing at 12 weeks after the last dose of treatment.	12 weeks post last dose of treatment with DAA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events	Safety and tolerability of DAA therapy in the lung transplant recipient monitored by quantifying the number of treatment related adverese events per patient and evaluation clinically significant out of range lab results as compared to baseline/pretreatment values per patient	8 weeks
Tolerability (Based on Number of Adverse Events and Clinically Significant Laboratory Values)	Tolerability of commercially available DAA therapy in the lung transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating clinically significant laboratory results	8 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2019
• Primary Completion (Actual): April 4, 2022
• Study Completion (Actual): April 4, 2022

Study Registration Dates

• First Submitted: July 30, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: HCV; Hepatitis C; Lung Transplant; Lung disease
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Respiration Disorders; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Respiratory Insufficiency; Anti-Infective Agents; Sofosbuvir-velpatasvir drug combination; Antiviral Agents
• Other Study ID Numbers: 2018P001697

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anticipate to share coded data with collaborators
• IPD Sharing Time Frame: Anticipate data would be available to share within 6 months after the final patient completes the study.
• IPD Sharing Access Criteria: Coded data would be shared with collaborators who have received IRB approval to use the data and have been approved by the PI for their collaboration.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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