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

• ClinicalTrials.gov Identifier: NCT03625687
• Recruitment Status: Enrolling by invitation
• First Posted: August 10, 2018
• Last Update Posted: April 8, 2021
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Raymond Chung, Massachusetts General Hospital

Study Description

Brief Summary:

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 12 weeks of commercially available DAA therapy to prevent HCV transmission upon transplantation.

Condition or disease	Intervention/treatment	Phase
Respiratory Failure; Hepatitis C	Drug: Clinically prescribed direct acting antiviral (Mavyret or Epclusa) HCV treatment for 12 weeks	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Pan-genotypic Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Lung Transplant
• Actual Study Start Date: February 5, 2019
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: April 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment with Direct Acting Antiviral for HCV; 12 weeks of treatment with HCV Direct Acting Antiviral tablet (Mavyret or Epclusa)	Drug: Clinically prescribed direct acting antiviral (Mavyret or Epclusa) HCV treatment for 12 weeks; 12 weeks of direct acting antiviral treatment based on clinical indication (either Mavyret or Epclusa); Other Names: DAA treatment; Mavyret; Epclusa

Outcome Measures

Primary Outcome Measures :

1. Undetectable blood HCV RNA level [ Time Frame: 12 weeks post treatment ]
   Negative HCV RNA by blood testing at 12 weeks after the last dose of treatment.

Secondary Outcome Measures :

1. Safety (based on number of adverse events and clinically significant lab values) of DAA therapy in patients undergoing lung transplantation [ Time Frame: 12 weeks ]
   Safety 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 as compared to baseline/pretreatment values per patient.
2. Tolerability (based on number of adverse events and clinically significant laboratory values) [ Time Frame: 12 weeks ]
   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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Raymond T Chung, MD; Massachusetts General Hospital

More Information

• Responsible Party: Raymond Chung, Director of Hepatology, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03625687
• Other Study ID Numbers: 2018P001697
• First Posted: August 10, 2018
• Last Update Posted: April 8, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anticipate to share coded data with collaborators
• Supporting Materials: Study Protocol
• Time Frame: Anticipate data would be available to share within 6 months after the final patient completes the study.
• 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.

• 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

Keywords provided by Raymond Chung, Massachusetts General Hospital:

Lung disease; Lung Transplant; HCV; Hepatitis C

Additional relevant MeSH terms:

Hepatitis C; Hepatitis; Respiratory Insufficiency; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Respiration Disorders; Respiratory Tract Diseases; Antiviral Agents; Sofosbuvir-velpatasvir drug combination; Anti-Infective Agents