Conditions: Hepatitis C, Chronic Lung Transplant
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 1
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate whether treatment with Epclusa (sofosbuvir/velpatasvir) after lung transplantation in individuals with chronic hepatitis C infection is feasible, safe and effective at curing HCV.

Detailed description:

Arms:
arm 1: Epclusa (sofosbuvir 400mg/velpatasvir 100mg) 1 tablet oral or via tube daily for 12 weeks, taken with or without food.

Interventions: intervention 1: Epclusa
Intervention descriptions: intervention 1: Patients will be treated with this drug for 12 weeks post lung transplant.

Protocol document:
Prot_SAP_000.pdf: 
Page | 1 
10May2018 
 
 Protocol Title 
Lung Transplantation in Chronic Hepatitis C Infection with Post Transplant EPCLUSA 
Treatment: A Pilot Feasibility and Efficacy Study 
 
Purpose of the Study 
Primary objectives 
 Assess feasibility, safety and efficacy of Epclusa treatment after lung transplant in those 
with chronic Hepatitis C Virus infection.   
 Establish Sustained Virologic Response (SVR)12 rates in HCV-infected lung transplant 
recipients treated with EPCLUSA.  SVR 12 is the absence of detectable hepatitis C virus 
in the blood after 12 weeks of antiviral therapy.  This is the standard outcome in studies 
evaluating therapies to treat hepatitis C virus. 
 
Secondary Objective 
o Evaluate impact of considering donors who are hepatitis C nucleic acid 
amplification test (NAT) positive in recipients with pre-existing hepatitis C 
viremia on wait times and post transplant survival. 
 Are wait times shortened by considering HCV NAT positive donors? 
Do HCV NAT positive donors otherwise meet criteria for lung donation? 
 
Primary endpoints 
 Sustained Virologic Response 12 weeks (SVR 12) in those treated with EPCLUSA 
 Adverse events resulting in discontinuation of EPCLUSA 
 Eligibility for EPCLUSA treatment within 12 months of lung transplant.   
o If subjects do not have adequate renal function or require medications with 
significant drug interactions with epclusa, they will not be eligible for treatment.  
Eligibility is an outcome because it is not known if these factors will limit utility 
of epclusa in this setting due to common complications associated with lung 
transplantation. 
 
Secondary endpoints 
 Serum HCV RNA levels at 12-, 24-, and 48-weeks after initiation of EPCLUSA 
 Adverse events requiring temporary interruption in Epclusa therapy 
 90-day and 1-year post transplant patient survival 
 90-day and 1-year post transplant patient survival in recipients of HCV NAT positive 
donor organ 
 
Exploratory outcomes   
 Change in transient elastography score at 48-weeks post Epclusa treatment 


Page | 2 
10May2018 
 
 Acute rejection rates   
 Primary graft dysfunction scores 
 Infections requiring treatment 
 Wait times associated with donor HCV status 
 
Background & Significance 
Nearly 150,000 deaths are attributed to end stage lung disease annually in the United States.i  
Lung transplantation remains the only effective therapy for end stage lung disease, yet just over 
2000 were performed in the US in 2015 and hundreds of patients continue to die each year while 
awaiting a suitable organ.ii  This is related to a limited donor pool as well as strict inclusion 
criteria.  Active chronic hepatitis C infection in the recipient has been considered a 
contraindication to lung transplantation at most programs, however new highly effective direct-
acting antiviral (DAA) treatment regimens have changed the landscape of hepatitis C and prompt 
reconsideration of this practice.  More importantly, HCV is now a curable condition and these 
medications offer the promise of expanding the organ donor pool and increasing access to lung 
transplantation by utilizing HCV positive donors in HCV positive candidates. 
 
A single center, retrospective review out of Canada comparing lung transplant recipients with 
detectable HCV RNA at time of transplant (n=14) with those who were HCV antibody positive 
(n=13) and those who were HCV antibody negative (n=443), demonstrated no difference in 1-, 
3- and 5-year survival, in the absence of hepatitis-C directed treatment.iii  A review of the U.S. 
national experience comparing outcomes between lung transplant recipients who were HCV 
antibody positive and those who were HCV antibody negative between 2000-2011 similarly did 
not reveal a difference in median survival (4.4 vs 5.4 years, P=0.10), although HCV RNA status 
was not captured in this highly selected cohort, so extrapolation of this data is limited.iv    
 
In spite of this encouraging data, there is likely a negative long term impact from untreated HCV 
infection as demonstrated by 15% worse 10-year survival in kidney transplant recipients with 
chronic HCV infection compared with those who are HCV negativev as well as the overall 
mortality rates associated with HCV in the general population.  Additionally, liver function is a 
legitimate concern given reports of acute worsening hepatic fibrosis in lung transplant recipients 
with HCV.vi vii  DAA regimens to cure HCV result in improved liver function and survival in 
non-transplant populations and a retrospective study has demonstrated efficacy and safety of 
DAA regimens to treat HCV infection after renal transplantation.viii  Presumably, viral clearance 
will optimize outcomes for these individuals post-transplant.    
 
Given the promising initial reports, many renal transplant centers are now using HCV positive 
donors in order to minimize wait times for their HCV positive recipients, and then treating them 
with DAA regimens post-transplant to clear the HCV infection and preserve liver function.  This 
strategy appears to be both safe and effective based on a single center retrospective review of 43 


Page | 3 
10May2018 
 
renal transplant recipients, 19 of whom received organs from HCV antibody positive donors who 
were treated with 4 different DAA regimens.  100% of the patients in this cohort achieved SVR 
12, regardless of DAA regimen used, immunosuppressive induction agent or HCV status of 
donor.  While wait times were significantly shorter in the HCV-positive donor cohort (median 
485 days vs 969 days), there was no difference in allograft function or patient survival post-
transplant.ix   
 
Lung transplant recipients require the highest levels of maintenance immunosuppression for 
solid organ transplant; therefore, establishing efficacy in this population is critical for the solid 
organ transplant community as a whole.  It is also an important and necessary step in working 
towards more widespread use of HCV positive donors.   Again, this is particularly relevant in 
lung transplantation as lungs remain the least likely of the commonly transplanted organs to be 
utilized with only 17% of multi-organ donors providing lungs.  HCV positive donors are 
routinely turned down due to published reports describing notably worse survival and major liver 
complications in HCV negative recipients receiving lungs from HCV positive donors,x however 
the potential to treat and make these lungs useful could revolutionize solid organ transplant and 
save thousands of lives.   
 
Epclusa is a fixed-dose combination product containing sofosbuvir, an HCV NS5B polymerase 
inhibitor, and velpatasvir, an HCV NS5A inhibitor.  It was approved by the FDA in June 2016 
for the treatment of chronic HCV genotypes 1, 2, 3, 4, 5 and 6.  The first antiviral approved to 
treat all major forms of HCV, it can be used in patients with compensated and uncompensated 
cirrhosis, as well as those without cirrhosis.  Response rates, defined as a RCV RNA pcr less 
than the lower limit of quantification (<LLOQ) 12 weeks after completion of therapy (SVR12), 
in those without decompensated cirrhosis who were treated for 12 weeks range from 94-99%.  It 
is recommended as first line therapy by the American Association for the Study of Liver 
Diseases (AASLD) and the Infectious Diseases Society of America (ISDA) for treatment of 
chronic HCV infection with genotypes 1, 2, 3, 4, 5 and 6. 
 
The goal of this study is to assess whether a strategy of performing lung transplant in individuals 
with end stage lung disease and chronic HCV infection, and then treating them post-transplant 
with Epclusa is feasible, safe and effective at curing HCV. 
 
The reason to wait until after lung transplant to treat the hepatitis C virus is two-fold.  First, it 
opens up the donor pool to include those with chronic hepatitis C.  This can potentially shorten 
wait times and increase the number of lungs used for transplantation, which could increase 
access to a life-saving transplant and for those suffering with end stage lung disease and decrease 
deaths on the waiting list.  The second reason to adopt this strategy is that it allows those with 
rapidly progressive lung disease to be transplanted prior to completing 12 weeks of antiviral 


Page | 4 
10May2018 
 
therapy, during which time their lung disease might progress to the point where they are too sick 
to survive a lung transplant. 
 
As a first step, this study includes only lung transplant candidates with chronic HCV infection.  
For these candidates with chronic HCV infection, consideration would be given to organ offers 
from both HCV NAT positive and HCV NAT negative donors.  Donors would be accepted based 
on quality and suitability, independent of HCV status.  There would be no intentional utilization 
of an HCV positive donor into an HCV negative recipient. 
 
Design & Procedures 
Prospective, open-label study evaluating feasibility, safety and efficacy of Epclusa treatment in 
lung transplant recipients.  Lung transplant recipients who are chronically infected with hepatitis 
C virus will be treated with Epclusa for 12 weeks and evaluated for evidence of hepatitis C virus 
in their blood at 12, 24 and 48 weeks after therapy initiation.   
 
Individuals with chronic hepatitis C infection will be enrolled prior to transplant.  Participation in 
this study will allow individuals with active chronic hepatitis C infection to be considered for 
candidacy for lung transplant, as chronic HCV infection has, until this study, been considered a 
contraindication for lung transplant at Duke.   
 
Once the subject has undergone lung transplant, been discharged from the hospital and clinically 
stabilized (a process that can take weeks to months, depending on complications associated with 
this lung transplant), the subject will be referred for treatment screening.  A regaining of 
functional status, increasing independence in activities of daily living, and a lack of significant or 
poorly controlled acute infections or need for hospitalization are markers of clinical stability 
which will be determined by the treating transplant pulmonologist. 
 
If eligible, the subject will then be given study drug which will be taken for 12 weeks.  Subject 
will be monitored throughout treatment course for adverse events.  Upon completion of therapy, 
repeat testing will be performed to assess for clearance of the virus from the blood.  Subjects will 
be followed for 48 weeks after initiation of study drug to monitor for recurrence and to evaluate 
change in degree of liver stiffness, as assessed by transient elastography. 
 
Regimen (drug/dose/frequency) 
Epclusa (sofosbuvir 400mg/velpatasvir 100mg) 1 tablet PO or VT daily x 12 weeks, taken with 
or without food. 
 
Projected duration of treatment 
12 weeks 
 


Page | 5 
10May2018 
 
Projected duration of enrollment 
2 years 
 
Study Details 
 Treating pulmonologist will refer for treatment screening visit when clinically 
appropriate.  Repeat HCV PCR and genotyping will be done prior to start of Epclusa 
treatment.as part of the treatment screen.  
 Drug-drug interaction considerations: Many lung transplant recipients develop atrial 
fibrillation after lung transplant and may require treatment with amiodarone.  Due to risk 
of bradycardia associated with concomitant use of epclusa and amiodarone, subjects must 
be off amiodarone for at least 60 days in order to be eligible for epclusa treatment.   
 After 5 subjects complete 12 weeks of epclusa treatment, a preplanned analysis will be 
performed to assess safety and efficacy. 
 HCV positive donors will have blood collected at time of procurement to be sent for 
genotyping and quantitative PCR. 
 Because Epclusa is FDA-approved for all HCV genotypes, there is no anticipated safety 
risk associated with the organ donor having a different genotype than recipient. 
 
Early discontinuation 
If a subject decides to withdraw from the study prior to completion, the subject will be asked to 
return for a final visit for data collection.   
 
Selection of Subjects 
Inclusion criteria: 
1. HCV RNA >= 10^3 IU/ml at screening 
2. Chronic HCV infection, defined as positive HCV antibody and/or HCV RNA more than 
6 months prior to screening 
3. HCV Genotype 1, 2, 3, 4, 5 or 6 
4. Otherwise eligible for lung transplant at study site 
 
Exclusion criteria: 
1. Age <18  
2. Treatment with any of the following agents: 
o Amiodarone.  Subjects previously treated with amiodarone must have stopped the 
amiodarone at least 60 days prior to day 1 SOF/VEL 
o Carbamazepine, phenytoin, phenobarbital, oxcarbazepine 
o Rifabutin, rifampin or rifapentine 
o HIV regimens containing tenofovir, tipranavir/ritonavir, or efavirenz 
o St John’s wort 
o Modafinil 


Page | 6 
10May2018 
 
3. Have any serious or active medical or psychiatric illness which, in the opinion of the 
investigator, would interfere with subject treatment, assessment or compliance 
4. Hepatitis B surface antigen positive (This is checked at the time of transplant evaluation.) 
. ( 
5. History of hepatic encephalopathy or variceal hemorrhage 
6. Abnormal hematological and biochemical parameters, including: 
o Hemoglobin <8g/dL 
o Platelets <= 50,000/mm^3 
o ALT (alanine aminotransferase), AST (aspartase aminotransferase) or alkaline 
phosphatase >=10 times ULN 
o Total bilirubin >3mg/dL 
o Severe renal impairment, ie creatinine clearance (CrCl) <30mL/min 
7. Pregnant women or women planning to become pregnant 
8. Women who are breastfeeding 
9. Active or recent history (<=1 year) of drug or alcohol abuse 
 
Subject Recruitment and Compensation 
10 subjects will be enrolled. Subjects will be identified during the transplant evaluation phase by 
the clinical team.  The clinical team will assess subject’s willingness to participate in the study 
prior to being approached by the research team.  Due to active chronic HCV infection currently 
being considered a contraindication to transplant at Duke, declining to enroll in the study may 
impact the subject’s candidacy for transplant.   The suitability for transplant is ultimately made 
by the Lung Transplant Team, and dependent on multiple factors.  Agreeing to participate in this 
study is not a guarantee for transplant.  Subjects will not be compensated for participating in this 
study; however, subjects will receive study drug free of charge.   
 
Consent Process – see Section 14 of the e-IRB submission form.  
 
Risk/Benefit Assessment 
The most common adverse reactions observed with treatment with EPCLUSA for 12 weeks are 
headache and fatigue.  Bradycardia can occur when taken with amiodarone.   
 
Hepatitis B virus reactivation: There have been case reports of hepatitis B reactivation with 
Epclusa treatment.  All subjects will be screened for hepatitis B prior to enrollment. 
 
Costs to the Subject 
There will no additional costs to the subjects as a result of participating in this study.  Every 
attempt will be made to coordinate study visits with routine clinical care.   
 
Data Analysis & Statistical Considerations 


Page | 7 
10May2018 
 
This study is a small, pilot feasibility study and therefore not powered for comparative statistics.  
Descriptive and non-parametric statistics will be performed.  A matched, case-control cohort will 
based on age and underlying lung disease from same center over same time period will be used 
to evaluate survival outcomes.  An unadjusted Kaplan-Meier survival analysis for cumulative 
survival will be performed. 
 
Data & Safety Monitoring 
In accordance with federal regulations the PI will monitor for, review, and promptly report to the 
IRB, appropriate institutional officials, sponsor, coordinating center and the appropriate 
regulatory agency head all unanticipated problems involving risks to subjects or others that occur 
in the course of a subject’s participation in a research, all AE reports will be reported per the 
DUHS IRB policies. 
 
Data collection, storage and confidentiality 
 All data collected in the case report forms (CRF) will be by review of the subject’s Duke 
medical record documentation or through patient interview.  All subjects will be given a 
study ID in order to protect PHI. This will be stored on a secure study drive. 
 The CRF will be built into a password protected REDCap database behind the Duke 
firewall. 
 All paper forms will be stored in a locked cabinet in the research team’s locked office. 
Schedule of Assessments: 
 
Screening Visit 
Informed consent will be reviewed with the subject. After informed consent is signed, subjects 
will be assessed for eligibility for inclusion into the trial. 
The following data will be collected from the subject’s medical chart: 
 Medical and medication history  
 Liver biopsy results 
 FibroScan results 
 Laboratory results 
 EKG results 
 
Treatment Screening Visit 
After the lung transplant subjects will have a treatment screening visit.  
The following tests and procedures will be done at this visit as part of standard of care: 
 Physical exam   
 Vital Signs 
 Routine blood tests will be collected (CBC, CMP, Mg, and PT/INR).  
 Medical history will be reviewed. 
 


Page | 8 
10May2018 
 
The following tests and procedures will be done at this visit for research purposes: 
 Female subjects of  child-bearing potential will have serum beta HCG test 
Female subjects are considered “of child-bearing potential” if they (a) are anatomically and 
physiologically capable of becoming pregnant and (b) they will be, or could possibly be, 
engaging in sexual activity with males while study interventions that pose the possibility of harm 
to a fetus are occurring. Sterilization (tubal ligation/cauterization or vasectomy of the male 
partner), while highly effective, does not perfectly prevent pregnancy. Women using these 
contraceptive methods are considered “of child-bearing potential.” 
 
Women are considered past the age of “child-bearing potential” if 
 they are greater than 55 years of age, OR 
o they are at least 50 years of age AND 
o have not menstruated for at least 12 months, OR 
o have a documented Follicule Stimulating Hormone (FSH) level of greater than 40 
mIU/mL. 
 they are at least 45 years of age AND 
o have not menstruated for at least 18 months, OR 
o have a documented Follicule Stimulating Hormone (FSH) level of greater than 40 
mIU/mL. 
 A blood sample will be collected for HCV status. 
 EKG  
 If the subject is eligible to start Epclusa treatment a 6 week supply will be dispensed. A 
drug log will be provided to the subject for accountability purposes. 
 Concomitant medications will be review 
 Clinical data related to transplant and donor will be collected from subject’s medical 
chart. 
 
 
 


Page | 9 
10May2018 
 
Treatment Initiation  
Subjects will be started on EPCLUSA treatment. Treatment consists of 1 pill taken by mouth 
once a day, either with or without food.  Treatment will last 12 weeks. This visit can be 
combined with the treatment screening visit if subjects are eligible at that time. 
 
Week 4 
The following tests and procedures will be done at this visit as part of standard of care: 
 Physical exam  
 Vital Signs 
Routine blood tests will be collected (CBC, CMP, Mg, and PT/INR).The following will be done at 
this visit for research purposes: 
 Dispense 6 weeks supply of Epclusa. 
 Drug accountability review 
 Adverse Events (AE) assessment 
 Concomitant medications review 
 
Week 8 
The following tests and procedures will be done at this visit as part of standard of care: 
 Physical exam  
 Vital Signs 
 Routine blood tests will be collected (CBC, CMP, Mg, and PT/INR). 
 
The following will be done at this visit for research purposes: 
 AE assessment 
 Concomitant medications review 
 
Week 12 
The following tests and procedures will be done at this visit as part of standard of care: 
 Physical exam  
 Vital Signs 
 Routine blood tests will be collected (CBC, CMP, Mg, and PT/INR). 
 
The following test and procedures will be done at this visit for research purposes: 
 A blood sample will be collected for HCV status.  
 Drug accountability review 
 AE assessment 
 Concomitant medications review 
 
 
 


Page | 10 
10May2018 
 
Week 24 
The following tests and procedures will be done at this visit as part of standard of care: 
 Physical exam  
 Vital Signs 
 Routine blood tests will be collected (CBC, CMP, Mg, and PT/INR). 
 
The following test and procedures will be done at this visit for research purposes: 
 A blood sample will be collected for HCV status.  
 AE assessment 
 Concomitant medications review 
 
Week 48 
The following tests and procedures will be done at this visit as part of standard of care: 
 Physical exam  
 Vital Signs 
 Routine blood tests will be collected (CBC, CMP, Mg, and PT/INR). 
 
The following test and procedures will be done at this visit for research purposes: 
 A blood sample will be collected for HCV status.  
 AE assessment 
 Concomitant medications review 
 Transient Elastography 
 
 
 


Page | 11 
10May2018 
 
Schedule of Assessments  
 
Study Week 
+/- 21 days 
Lung 
transplant 
evaluation 
Study 
Screening 
Transplant 
Treatment 
Screening Visit 
Treatment initiation 
(can be combined with 
treatment screening) 
Week 4 
 
Week 8 
 
Week 12 
 
Week 24 
 
Week 48 
 
Study Informed 
consent 
 
X 
 
 
 
 
 
 
 
 
Inclusion/Exlusio
n 
 
X 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
Medical history 
 
 
 
X 
 
 
 
 
 
 
Physical exam 
X 
 
 
X 
 
X 
X 
X 
X 
X 
Vital Signs 
Height/Weight 
X 
 
 
X 
 
X 
X 
X 
X 
X 
Confirm 
treatment 
eligibility 
 
 
 
X 
 
 
 
 
 
 
Serum HCG 
 
 
 
X 
 
 
 
 
 
 
Liver biopsy 
X 
 
 
 
 
 
 
 
 
 
Transient 
elastography 
X 
 
 
 
 
 
 
 
 
X 
HCV PCR 
X 
 
 
X 
 
 
 
X 
X 
X 
HCV genotype 
X 
 
 
X 
 
 
 
 
 
 
Routine labs 
(CBC, CMP, Mg, 
PT/INR) 
X 
 
 
X 
 
X 
X 
X 
X 
X 
Drug and alcohol 
Screen 
X 
 
 
 
 
 
 
 
 
 
Hepatitis B 
Screen 
X 
 
 
 
 
 
 
 
 
 
EKG 
X 
 
 
X 
 
 
 
 
 
 
Dispense Drug 
 
 
 
 
X (6 week supply) 
X (6 week 
supply) 
 
 
 
 
Review Con 
Meds 
 
 
 
X 
 
X 
X 
X 
X 
X 
Review for AEs 
 
 
 
 
 
X 
X 
X 
X 
X 
Donor HCV 
PCR/genotype (if 
donor HCV NAT 
positive) 
 
 
X (At time of 
procurement) 
 
 
 
 
 
 
 
*All follow-up visits may occur inpatient or outpatient.  
*Boxes marked in red are part of standard of care for lung tx candidates/recipients. 


Page | 12 
10May2018 
 
 
 
Note: To ensure compliance with CMS guidelines, all studies involving patient care at Duke are 
required to have study protocol-specific EMR build for ordering, resulting and billing of 
protocol-related activities.  This ensures SOC activities are billed to insurance and protocol-
related activities are billed to the study.  This is referred to as EPIC initiation.  The EPIC build is 
specific to each protocol and will not be used for any future studies. 
 
 
 
References 
i http://www.cdc.gov/nchs/fastats/copd.htm 
ii https://www.unos.org/about/annual-report/ 
iii Doucette KE1, Halloran K2, Kapasi A2, Lien D2, Weinkauf JG2. Outcomes of Lung Transplantation in Recipients with Hepatitis C 
Virus Infection. Am J Transplant. 2016 Mar 21 [Epub ahead of print]. 
 
iv Englum BR1, Ganapathi AM2, Speicher PJ2, Gulack BC2, Snyder LD3, Duane Davis R2, Hartwig MG2. Impact of donor and recipient 
hepatitis C status in lung transplantation. J Heart Lung Transplant. 2016 Feb;35(2):228-35 
v J. Levitsky, K. Doucette. AST Infectious Diseases Community of Practice. Viral hepatitis in solid organ transplantation. Am 
J Transplant, 13 (Suppl 4) (2013) 147-68. 
vi Doucette K1, Sumner S2, Weinkauf J3. Treatment of hepatitis C in a lung transplant recipient with sofosbuvir and 
daclatasvir. J Heart Lung Transplant. 2016 Feb 8. pii: S1053-2498(16). [Epub ahead of print]. 
vii Hartwig MG, Patel V, Palmer SM, Cantu E, Appel JZ, Messier RH, Davis RD.  Transplantation. Hepatitis B core antibody positive 
donors as a safe and effective therapeutic option to increase available organs for lung transplantation. 2005 Aug 15;80(3):320-5. 
viii Kamar N, Marion O, et al.  Efficacy and Safety of Sofosbuvir-Based Antiviral Therapy to Treat Hepatitis C Virus Infection After 
Kidney Transplantation. Am J Transplant. 2016 May;16(5):1474-9.. Epub 2015 Nov 20. 
 
ix Sawinski D1, Patel N1, Appolo B2, Bloom RD1. Use of HCV+ donors does not affect HCV clearance with directly acting antiviral 
therapy but shortens the wait time to kidney transplantation. Transplantation. 2016 Aug 4. [Epub ahead of print] 
 
x Englum BR1, Ganapathi AM2, Speicher PJ2, Gulack BC2, Snyder LD3, Duane Davis R2, Hartwig MG2. Impact of donor and recipient 
hepatitis C status in lung transplantation. J Heart Lung Transplant. 2016 Feb;35(2):228-35 
                                                           

ICF_001.pdf: 
 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
Page 1 of 9 
Subject*Initials_________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
 
You are being asked to take part in this research study because you have Hepatitis C (HCV) and are 
being considered for lung transplant.  Research studies are voluntary and include only people who 
choose to take part.  Please read this consent form carefully and take your time making your decision. 
As your study doctor or study staff discusses this consent form with you, please ask him/her to explain 
any words or information that you do not clearly understand.  We encourage you to talk with your 
family and friends before you decide to take part in this research study.  The nature of the study, risks, 
inconveniences, discomforts, and other important information about the study are listed below. 
 
Please tell the study doctor or study staff if you are taking part in another research study. 
 
Dr. Omar Mohamedaly will conduct the study and it is funded by Gilead Sciences.  This is an 
investigator sponsored study that was initiated by Dr. Mohamedaly.  Gilead Sciences will pay Duke 
University to perform this research, and these funds may reimburse part of Dr. Mohamedaly’s salary. 
 
WHO WILL BE MY DOCTOR ON THIS STUDY? 
If you decide to participate, Dr. Mohamedaly will be your doctor for the study and will be in contact 
with your regular health care provider throughout the time that you are in the study and afterwards, if 
needed. 
 
WHY IS THIS STUDY BEING DONE? 
Chronic active hepatitis C is currently considered a contraindication to lung transplant at most lung 
transplant centers, including Duke.  However, in recent years, a new class of medications, called direct 
CONCISE SUMMARY
The purpose of this study is to evaluate whether treatment with the direct acting antiviral (DAA) 
Epclusa (sofosbuvir/velpatasvir) after lung transplantation in individuals with chronic hepatitis C 
infection is feasible, safe and effective at curing HCV..
This study involves a screening visit prior to your lung transplant. It also involves an HCV treatment 
screening visit, an HCV treatment initiation visit that may be combined with the HCV treatment 
screening visit, and follow-up visits at week 4, week 8, week 12, week 24, and week 48. You will be 
treated with Epclusa for 12 weeks. Participants will be asked to provide blood samples for testing 
and will undergo tests, exams, and procedures for study purposes.  
There are risks associated with Epclusa. Some risks include: headache, fatigue, nausea, asthenia, and 
insomnia. 
If you are interested in learning more about this study please continue reading.
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019


 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
Page 2 of 9 
Subject*Initials_________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
acting antiviral (DAA) therapies have been approved by the U.S. Food and Drug Administration (FDA) 
and been proven to be highly effective at curing hepatitis C infection.  There have been no formal 
clinical studies evaluating whether those with end stage lung disease and hepatitis C can safely undergo 
lung transplant and then treated and cured of the hepatitis C infection after transplant using a DAA 
regimen.   
 
The purpose of this study is to evaluate whether treatment with the direct acting antiviral (DAA) Epclusa 
(sofosbuvir/velpatasvir) after lung transplantation in individuals with chronic hepatitis C infection is 
feasible, safe and effective at curing HCV. Epclusa is approved by the FDA for the treatment of chronic 
Hepatitis C (HCV) infection.  
 
The current standard of care at Duke is not to transplant lungs from donors with known active 
hepatitis C or to perform lung transplant in recipients with chronic hepatitis C infection.    
Utilizing organs from hepatitis C donors into hepatitis C recipients is commonly done in 
abdominal transplant throughout the United States.  Data suggest this can result in shorter 
average wait times without other significant adverse results.  In this study, organ donors will be 
considered regardless of their hepatitis C status.  This will allow the surgeons to evaluate more 
donors to find high quality lungs that are a good match for you.  Other than donor HCV status, all 
lungs used for transplant will meet our standard criteria for donor lungs.  You will be 
transplanted using the first appropriate lungs for which you are eligible based on the national 
waitlist and organ allocation system. 
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
Approximately 10 people will take part in this study at Duke. 
 
WHAT IS INVOLVED IN THE STUDY? 
If you agree to be in this study, you will be asked to sign and date this consent form.   
 
Screening Visit (this visit occurs before your lung transplant) 
The following data will be collected from your medical chart: 
 Medical and medication history  
 Liver biopsy results 
 Transient Elastography (FibroScan) results – This is a non-invasive test that measures liver 
stiffness. 
 Laboratory results 
 EKG results 
 
HCV Treatment Screening Visit 
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019


 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
Page 3 of 9 
Subject*Initials_________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
Once you have recovered from your lung transplant, have been discharged from hospital, and are well 
enough to begin therapy in the opinion of your transplant physician and study doctor, you will be 
referred for the treatment screening visit.  
 
The following tests and procedures will be done at this visit: 
 A pregnancy test will be done on child bearing potential women (approximately ½ teaspoon/3 
mls).  
 A blood sample will be collected for HCV status (approximately 1½ teaspoons/8 mls).  
 EKG  
 If you are eligible to start Epclusa treatment a 6 week supply will be dispensed. You will be 
provided with a diary to keep track of when you take Epclusa. 
 Your medication list will be reviewed. 
 Clinical data related to transplant and donor will be collected from your medical chart. 
 
HCV Treatment Initiation Visit 
You will be started on EPCLUSA treatment. Treatment consists of 1 pill taken by mouth once a day, 
either with or without food.  Treatment will last 12 weeks. This visit can be combined with the treatment 
screening visit if you are eligible at that time. 
 6 weeks of Epclusa treatment will be dispensed for you to take at home. 
 
Week 4 
The following will be done at this visit: 
 Dispense 6 weeks supply of Epclusa. 
 Your study drug diary will be reviewed.  
 You will meet with the study coordinator to review medications, side effects and changes in your 
health. 
 
Week 8 
The following will be done at this visit: 
 You will meet with the study coordinator to review medications, side effects and changes in your 
health. 
 Your study drug diary will be reviewed.  
 
Week 12 
The following test and procedures will be done at this visit: 
 A blood sample will be collected for HCV status (approximately ½ teaspoon/3 mls).  
 Your study drug diary will be reviewed.  
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019


 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
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 You will meet with the study coordinator to review medications, side effects and changes in your 
health. 
 
Week 24 
The following test and procedures will be done at this visit: 
 A blood sample will be collected for HCV status (approximately ½ teaspoon/3 mls).  
 You will meet with the study coordinator to review medications, side effects and changes in your 
health. 
 
Week 48 
The following test and procedures will be done at this visit: 
 A blood sample will be collected for HCV status (approximately ½ teaspoon/3 mls).  
 You will meet with the study coordinator to review medications, side effects and changes in your 
health. 
 Transient Elastography (FibroScan).  This is a non-invasive test to measure liver stiffness. 
 
 
The total amount of blood taken from you throughout the entire study for research purposes only is 
approximately 20 mls (4 teaspoons).  
 
HOW LONG WILL I BE IN THIS STUDY? 
Your participation in this study will be approximately 1 year. You can choose to stop participating at 
any time without penalty or loss of any benefits to which you are entitled. However, if you decide to 
stop participating in the study, we encourage you to talk to your doctor first.  
 
WHAT ARE THE RISKS OF THE STUDY? 
As a result of your participation in this study, you are at risk for the following side effects. You should 
discuss these with the study doctor and your regular health care provider if you choose. 
 
What are the risks of lung transplantation with HCV? 
The risks of lung transplantation in individuals with hepatitis C does not appear to be significantly 
different from those without hepatitis C. A review of the U.S. national experience comparing outcomes 
between lung transplant recipients who were HCV antibody positive and those who were HCV antibody 
negative between 2000-2011 did not reveal a difference in median survival.  
 
Risks of Epclusa 
Common (10% or above) 
 Headache 
 Fatigue 
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019


 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
Page 5 of 9 
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 Slow heart rate (bradycardia) may occur if Epclusa is taken with amiodarone, a medicine used to 
treat certain heart conditions.     
 
Less common (5% to 9%) 
 Nausea 
 Asthenia (weakness, lack of energy) 
 Insomnia (difficulty sleeping) 
 
Hepatitis B virus reactivation:  f you have ever had hepatitis B, the hepatitis B virus could become active 
again during and after treatment with EPCLUSA. You will have been assessed for hepatitis B as part of 
your lung transplant evaluation.  If this testing showed evidence of hepatitis B infection, you will not be 
able to participate in this study. 
 
Risks of Drawing Blood 
Risks associated with drawing blood from your arm include momentary discomfort and/or bruising. 
Infection, excess bleeding, clotting, or fainting are also possible, although unlikely. 
 
Risks of ECG 
Possible side effects of the ECG are skin irritation, itching and redness from the ECG electrode pads. 
 
Risks of Reproductive Potential 
Female 
Being a part of this study while pregnant may expose the unborn child to significant risks, some of 
which may be currently unforeseeable.  Therefore, pregnant women will be excluded from the study.  If 
you are a woman of childbearing potential, a blood pregnancy test will be done (using 1 teaspoon of 
blood drawn from a vein by needle-stick), and it must be negative before you can continue in this study.  
If sexually active, you must agree to use appropriate contraceptive measures for the duration of the 
study. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or 
hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or 
injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an 
intrauterine device (IUD). Contraceptive measures such as Plan B (TM), sold for emergency use after 
unprotected sex, are not acceptable methods for routine use.  If you do become pregnant during this 
study or if you have unprotected sex, you must inform your study physician immediately. 
 
Drug and Food Interactions:  
For your safety, you must tell the study doctor or nurse about all the prescribed medical foods and drugs, 
herbal products, over-the-counter (OTC) drugs, vitamins, natural remedies, and alcohol that you are 
taking before you start the study and before starting to take any of these products while you are on the 
study. 
 
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019


 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
Page 6 of 9 
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There may be risks, discomforts, drug interactions or side effects that are not yet known. 
 
WHAT ALTERNATIVES ARE THERE TO PARTICIPATION IN THIS STUDY? 
Instead of being in this study, you could choose to be treated for hepatitis C prior to lung transplant 
evaluation.  You also could seek out consideration by other lung transplant programs.  Most programs in 
the United States have historically turned down candidates with active hepatitis C, however the 
Cleveland Clinic has transplanted patients with hepatitis C in the past.  Every lung transplant program 
has its own criteria for transplant listing which may change over time. 
 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY? 
If you agree to take part in this study, there may be direct medical benefit to you.  Duke is currently not 
transplanting individuals with chronic hepatitis C infection outside of this protocol, so participating in 
this study will make you eligible to be considered as a candidate for a lung transplant.  The suitability 
for transplant is ultimately made by the Lung Transplant Team, and dependent on multiple factors.  
Agreeing to participate in this study is not a guarantee for transplant.  Participating in this study will 
make you eligible to receive lungs from a donor with known HCV which may result in a shorter wait 
time. Previous studies have demonstrated that clearance of HCV virus is associated with decreased rates 
of death and cirrhosis, although this cannot be guaranteed. We hope that in the future the information 
learned from this study will benefit other people with your condition.  
 
WILL MY INFORMATION BE KEPT CONFIDENTIAL? 
Participation in research involves some loss of privacy. We will do our best to make sure that 
information about you is kept confidential, but we cannot guarantee total confidentiality. Your personal 
information may be viewed by individuals involved in this research and may be seen by people 
including those collaborating, funding, and regulating the study. We will share only the minimum 
necessary information in order to conduct the research. Your personal information may also be given out 
if required by law.  
 
As part of the study, Dr. Mohamedaly and his study team will report the results of your study-related 
laboratory tests and procedures to Gilead. In addition, your records may be reviewed in order to meet 
federal or state regulations.  Reviewers may include representatives from the Food and Drug 
Administration, representatives of Gilead and designees, and the Duke University Health System 
Institutional Review Board. If any of these groups review your research record, they may also need to 
review your entire medical record. 
 
The study results will be retained in your research record for at least six years after the study is 
completed.  At that time either the research information not already in your medical record will be 
destroyed or information identifying you will be removed from such study results at DUHS.  Any 
research information in your medical record will be kept indefinitely. 
 
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019


 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
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This information may be further disclosed by the sponsor of this study.  If disclosed by the sponsor, the 
information is no longer covered by federal privacy regulations. If this information is disclosed to 
outside reviewers for audit purposes, it may be further disclosed by them and may not be covered by the 
federal privacy regulations. 
 
While the information and data resulting from this study may be presented at scientific meetings or 
published in a scientific journal, your identity will not be revealed. 
 
Some people or groups who receive your health information might not have to follow the same privacy 
rules. Once your information is shared outside of DUHS, we cannot guarantee that it will remain private. 
If you decide to share private information with anyone not involved in the study, the federal law 
designed to protect your health information privacy may no longer apply to the information you have 
shared.  Other laws may or may not protect sharing of private health information 
 
WHAT ARE THE COSTS TO YOU? 
You or your insurance provider will be responsible and billed for all costs related to your routine 
medical care, including copayments and deductibles. Routine medical care services are those that you 
would have received for your condition if you were not participating in this research study. Not all 
services are covered by insurance.  Some procedures or scans may require pre-authorization by your 
insurance plan. We will notify you if we learn that a service is not covered by your insurance plan as 
part of the pre-authorization process. If it is not covered, you will be responsible for paying for it.  The 
amount of your out-of-pocket expense will depend on your insurance plan.  For beneficiaries with 
Medicare Advantage Plans, traditional Medicare is billed for the routine cost of a research study.  You 
may have more or higher co-pays than with a Medicare Advantage plan.  Please discuss the costs of the 
study with the study team. At your request, a Financial Counselor in the clinic may provide you with an 
estimate of costs for routine services. 
 
Gilead will provide the study drug free of charge to you. At the end of the study, or if you decide to 
withdraw from the study before it ends, you may be asked to return all unused study drug.  Your study 
doctor may request that you return for a checkup before you stop your study drug if she thinks that 
stopping it suddenly may harm you and may ask you to complete the tests that would ordinarily occur 
when a person completes the study. 
 
WHAT ABOUT COMPENSATION? 
There is no compensation for participation in this study. 
 
WHAT ABOUT RESEARCH RELATED INJURIES? 
Immediate necessary medical care is available at Duke University Medical Center in the event that you 
are injured as a result of your participation in this research study. However, there is no commitment by 
Duke University, Duke University Health System, Inc., or your Duke physicians to provide monetary 
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019


 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
Page 8 of 9 
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compensation or free medical care to you in the event of a study-related injury. The drug manufacturer, 
Gilead Sciences, Inc.will reimburse for the costs of medical care you receive foran illness or injury 
resulting solely from a defect in the study drug, Epclusa®, provided all aspects of the study protocol 
have been followed correctly.  
 
For questions about the study or research-related injury, contact Dr. Mohamedaly at (919) 684-6140 
during regular business hours. After hours and on weekends and holidays please call the Duke Hospital 
operator at (919) 684-8111 and ask to have Dr. Mohamedaly paged. 
 
WHAT ABOUT MY RIGHTS TO DECLINE PARTICIPATION OR WITHDRAW FROM THE 
STUDY? 
You may choose not to be in the study, or, if you agree to be in the study, you may withdraw from the 
study at any time. If you withdraw from the study, no new data about you will be collected for study 
purposes unless the data concern an adverse event (a bad effect) related to the study.  If such an adverse 
event occurs, we may need to review your entire medical record.  All data that have already been 
collected for study purposes, and any new information about an adverse event related to the study, will 
be sent to the study sponsor. 
 
Your decision not to participate or to withdraw from the study will not involve any penalty or loss of 
benefits to which you are entitled, and will not affect your access to health care at Duke. If you do 
decide to withdraw, we ask that you contact Dr. Mohamedaly in writing and let her know that you are 
withdrawing from the study. His mailing address is DUMC 102361, Durham, NC 27710. 
 
Dr. Mohamedaly may ask you to return for a checkup before you stop your study drug if he thinks that 
stopping the drug suddenly may harm you. He may also ask you to complete the tests that would 
ordinarily occur when a person completes the study. 
 
We will tell you about new information that may affect your health, welfare, or willingness to stay in 
this study. 
 
Your doctor may decide to take you off this study medication if your condition gets worse, if you have 
serious side effects, or if your study doctor determines that it is no longer in your best interest to 
continue.  The sponsor or regulatory agencies may stop this study at any time without your consent. If 
this occurs, you will be notified and your study doctor will discuss other options with you. 
 
If you agree to allow your blood samples to be kept for future research, you are free to change your 
mind at any time.  We ask that you contact Dr. Mohamedaly in writing and let him know you are 
withdrawing your permission for your blood samples to be used for future research. His mailing address 
is DUMC 102361, Durham, NC 27710. At that time we will ask you to indicate in writing if you want 
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019


 
 
 
 
 
Consent to Participate in a Research Study 
Lung Transplantation in Chronic HCV Infection with Post Transplant EPCLUSA Treatment: A Pilot 
Feasibility and Efficacy Study 
 
Page 9 of 9 
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the unused blood samples destroyed or if your samples (having all identifying information removed that 
would link the sample to you) could be used for other research. 
 
A description of this clinical trial will be available on https://www.clinicaltrials.gov/ct2/home as 
required by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
For questions about the study or a research-related injury, or if you have problems, concerns, questions 
or suggestions about the research, contact Dr. Mohamedaly at (919) 684-6140 during regular business 
hours. After hours and on weekends and holidays please call the Duke Hospital operator at (919) 684-
8111 and ask to have Dr. Mohamedaly paged. 
 
For questions about your rights as a research participant, or to discuss problems, concerns or suggestions 
related to the research, or to obtain information or offer input about the research, contact the Duke 
University Health System Institutional Review Board (IRB) Office at (919) 668-5111. 
 
STATEMENT OF CONSENT 
The purpose of this study, procedures to be followed, risks and benefits have been explained to me. I 
have been allowed to ask questions, and my questions have been answered to my satisfaction. I have 
been told whom to contact if I have questions, to discuss problems, concerns, or suggestions related to 
the research, or to obtain information or offer input about the research. I have read this consent form and 
agree to be in this study, with the understanding that I may withdraw at any time. I have been told that I 
will be given a signed and dated copy of this consent form. 
 
__________________________________________ 
 
___________     ____________ 
Signature of Subject  
 
 
 
 
 
Date 
 
   Time 
 
 
_________________________________________ 
Printed Name of Subject 
 
 
__________________________________________ 
 
___________     ____________ 
Signature of Person Obtaining Consent 
 
 
 
Date 
 
   Time 
 
 
__________________________________________ 
Printed Name of Person Obtaining Consent
DUHS IRB
IRB NUMBER: Pro00074361
IRB APPROVAL DATE: 08/28/2018
IRB EXPIRATION DATE: 08/10/2019