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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Respiratory Failure, Hepatitis C

Intervention / Treatment
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* Drug: Clinically prescribed direct acting antiviral (Mavyret or Epclusa) HCV treatment for 8 weeks


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with Direct Acting Antiviral for HCV<br>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<br>* 8 weeks of direct acting antiviral treatment based on clinical indication (either Mavyret or Epclusa)<br>* Other names: Epclusa;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung disease, Lung Transplant, HCV, Hepatitis C