Lung Transplantation in Chronic HCV Infection With Post Transplant EPCLUSA Treatment

• Epclusa (Drug): Patients will be treated with this drug for 12 weeks post lung transplant.

Primary outcomes

• Number of Participants With Sustained Virologic Response 12 Weeks (SVR 12) in Those Treated With EPCLUSA. [12 weeks]: Sustained Virologic Response 12 weeks (SVR 12) in those treated with EPCLUSA.
• Number of Patients That Reported an Adverse Event Resulting in Discontinuation of EPCLUSA [1 year]: Adverse events resulting in discontinuation of EPCLUSA
• Number of Patients Eligible for EPCLUSA Treatment [within 12 months of lung transplant]: Eligibility for EPCLUSA treatment within 12 months of lung transplant

Secondary outcomes

• Change in Serum HCV RNA Levels [12, 24, and 48 weeks after initiation of EPCLUSA]: Serum HCV RNA levels at 12-, 24-, and 48-weeks after initiation of EPCLUSA
• Number of Participants With Adverse Events Requiring Temporary Interruption of EPCLUSA Therapy [1 year]: Adverse events requiring temporary interruption in EPCLUSA therapy
• Patient Survival [90 days post-transplant]: 90-day post transplant patient survival
• Patient Survival [1 year post-tranplant]: 1 year post transplant patient survival
• Patient Survival [90 days post-transplant]: 90-day post transplant patient survival in recipients of HCV NAT positive donor organ
• Patient Survival [1 year post-transplant]: 1 year post transplant patient survival in recipients of HCV NAT positive donor organ

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* HCV RNA >= 10\^3 IU/ml at screening
* Chronic HCV infection, defined as positive HCV antibody and/or HCV RNA more than 6 months prior to screening
* HCV Genotype 1, 2, 3, 4, 5 or 6
* Otherwise eligible for lung transplant at study site

Exclusion Criteria:

* Age <18
* Treatment with any of the following agents:

  * Amiodarone. Subjects previously treated with amiodarone must have stopped the amiodarone at least 60 days prior to day 1 SOF/VEL
  * Carbamazepine, phenytoin, phenobarbital, oxcarbazepine
  * Rifabutin, rifampin or rifapentine
  * HIV regimens containing tenofovir or tipranavir/ritonavir
  * St John's wort
  * PPIs, including: Omeprazole, pantoprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole
  * Modafinil
* Have any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment or compliance
* Hepatitis B surface antigen positive
* History of hepatic encephalopathy or variceal hemorrhage
* Abnormal hematological and biochemical parameters, including:

  * Hemoglobin <8g/dL
  * Platelets <= 50,000/mm\^3
  * ALT (alanine aminotransferase), AST (aspartase aminotransferase) or alkaline phosphatase >=10 times ULN
  * Total bilirubin >3mg/dL
  * Severe renal impairment, ie creatinine clearance (CrCl) <30mL/min
* Pregnant women or women planning to become pregnant
* Women or are breastfeeding
* Active or recent history (<=1 year) of drug or alcohol abuse

Participant flow

Outcome results

• Number of Participants With Sustained Virologic Response 12 Weeks (SVR 12) in Those Treated With EPCLUSA. (Primary), Count of participants, Participants: Epclusa 1
• Number of Patients That Reported an Adverse Event Resulting in Discontinuation of EPCLUSA (Primary), Count of participants, Participants: Epclusa 0
• Number of Patients Eligible for EPCLUSA Treatment (Primary), Count of participants, Participants: Epclusa 1
• Change in Serum HCV RNA Levels (Secondary), Number, IU/mL: Epclusa NA
• Number of Participants With Adverse Events Requiring Temporary Interruption of EPCLUSA Therapy (Secondary), Count of participants, Participants: Epclusa 0
• Patient Survival (Secondary), Count of participants, Participants: Epclusa 1
• Patient Survival (Secondary), Count of participants, Participants: Epclusa 1
• Patient Survival (Secondary), Count of participants, Participants: Epclusa 1
• Patient Survival (Secondary), Count of participants, Participants: Epclusa 1

Adverse events

Time frame: 11 months

Limitations and caveats: Enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results.

• Study Protocol and Statistical Analysis Plan (PDF, 2018-05-10)
• Informed Consent Form (PDF, 2018-08-28)

• Omar Mohamedaly, MD, Principal investigator, Duke Heath