Clinical trial NCT03057847
Conditions: Hepatitis C, Chronic Opioid-use Disorder
Sponsor: Elizabeth Krans, MD
Start date: 2018-01-30; Completion date: 2022-02-24
Enrollment: 32 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Incorporating Hepatitis C Virus (HCV) treatment into opioid maintenance treatment program clinical protocols is an innovative health care delivery model that has been associated with improved HCV treatment uptake in non-pregnant, drug-using populations. This "medical home" approach would combine HCV and opioid maintenance treatment into one treatment regimen and incorporate the expertise of obstetricians, hepatologists, substance abuse treatment providers and pediatricians into one comprehensive clinical care model. The purpose of this study is to evaluate the feasibility/acceptability of a combined, peripartum HCV and opioid maintenance treatment program on adherence to HCV treatment regimens and evaluate the rate of intravenous drug use (IVDU) recidivism, HCV reinfection and health related Quality of Life (QOL) in women with opioid use disorder (OUD) during the first postpartum year.

The protocol involves three separate study phases. All 3 study phases will occur with support from hepatology providers at Magee-Womens Hospital. Phase 1 involves screening, enrollment and a baseline assessment of liver function, HCV infection (genotype, viral load) and blood and urine studies in HCV-infected patients during pregnancy. In Phase 2, subjects will undergo 12 weeks of sofosbuvir/velpatasvir therapy initiated at 2 weeks postpartum. Feasibility/acceptability and adherence to sofosbuvir/velpatasvir will be assessed at 4, 8 and 12 weeks of therapy. In Phase 3, subjects will continue to be followed for 15 months after treatment completion. Treatment effectiveness and sustained virologic response (SVR) will be evaluated at 3 months and rates of IVDU recidivism, HCV reinfection and patient centered outcomes such as health related quality of life (QOL) will be assessed at 6, 9 and 12 months following treatment completion.

Detailed description:

Arms: arm 1: Sofosbuvir/Velpatasvir, One tablet (400 mg of sofosbuvir and 100 mg of velpatasvir) taken orally once daily for 12 weeks in the postpartum period
Interventions: intervention 1: Sofosbuvir/Velpatasvir
Intervention descriptions: intervention 1: Sofosbuvir/Velpatasvir One tablet (400 mg of sofosbuvir and 100 mg of velpatasvir) taken orally once daily for 12 weeks in the postpartum period

Protocol documents:
Prot_SAP_000.pdf: 
SOF/VEL in postpartum women with OUD, Version 8.0 
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Management of HCV infection in pregnant and postpartum women with opioid use disorder: The 
potential of an integrated medical home model 
 
Phase IV Trial of Sofosbuvir/Velpatasvir Fixed Dose Combination in Postpartum Women with Chronic 
Hepatitis C Virus Infection 
 
Protocol version 8.0 
 
 
Funding Agencies: Gilead Sciences  
 
NCT03057847 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Contents 
 
LIST OF ABBREVIATIONS AND ACRONYMS ................................................................................................. 4 
RESEARCH TEAM ............................................................................................................................................ 5 
SUMMARY ........................................................................................................................................................ 5 
Table 1: Study Visit Schedule ......................................................................................................... 6 
KEY ROLES ...................................................................................................................................................... 8 
INTRODUCTION ............................................................................................................................................... 8 
Table 2: Study ASTRAL-1 .............................................................................................................10 
Table 3: Study ASTRAL-3: ............................................................................................................10 
OBJECTIVES .................................................................................................................................................. 11 
STUDY DESIGN.............................................................................................................................................. 11 
STUDY POPULATION .................................................................................................................................... 12 
STUDY MEDICATION ..................................................................................................................................... 14 
STUDY PROCEDURES .................................................................................................................................. 15 
Pre-screening ....................................................................................................................... 15 
Visit 1- Screening A (V1)....................................................................................................... 15 
Table 4: Screening Visit A (V1)......................................................................................................16 
Visit 2- Screening B (V2)....................................................................................................... 16 
Table 5: Screening Visit B (V2)......................................................................................................16 
Enrollment (V3) ..................................................................................................................... 17 
Table 6: Enrollment (V3)................................................................................................................17 
Treatment Initiation (V4) ....................................................................................................... 17 
Table 7: Treatment Initiation (V4) ..................................................................................................17 
Breastmilk Pharmacokinetics Substudy ................................................................................ 18 
 Table 8: Breastmilk Pharmacokinetics (PK1-5) .............................................................................19 
Follow up postpartum visits (Visits 5-9) ................................................................................. 19 
Table 9: Postpartum Follow-up Visits (V5-9) ..................................................................................19 
End of Treatment Visit (12 week postpartum follow-up, V10) ................................................ 20 
Table 10:  End of Treatment Visit ..................................................................................................20 
SVR Assessment (3 month post-treatment visit, V11) ........................................................... 20 
Table 11: SVR Assessment  (V11) ................................................................................................20 
6 month post-treatment visit (V12) ........................................... Error! Bookmark not defined. 
Table 12: 6 month post-treatment visit (V12) ................................... Error! Bookmark not defined. 
9 month post-treatment visit (V13) ........................................................................................ 20 
Table 13: 9 month post-treatment visit (V13) .................................................................................21 


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End of Study Visit (15 month post-treatment visit, V14) ........................................................ 21 
Table 14: End of Study visit (V14) .................................................................................................21 
Follow-up Procedures for Participants Who Permanently Discontinue Study Medication ...... 21 
Interim Visits ......................................................................................................................... 21 
Adherence Counseling and Assessment .............................................................................. 22 
In Depth Interviews and Qualitative Analysis ........................................................................ 22 
Clinical Evaluations and Procedures ..................................................................................... 22 
Laboratory Evaluations ......................................................................................................... 23 
Specimen Collection and Processing .................................................................................... 23 
Biohazard Containment ........................................................................................................ 23 
ASSESSMENT OF SAFETY ........................................................................................................................... 23 
CLINICAL MANAGEMENT .............................................................................................................................. 26 
STATISTICAL CONSIDERATIONS ................................................................................................................. 27 
DATA HANDLING AND RECORDKEEPING ................................................................................................... 29 
CLINICAL SITE MONITORING ....................................................................................................................... 30 
HUMAN SUBJECTS PROTECTIONS ............................................................................................................. 30 
PUBLICATION POLICY ................................................................................................................................... 34 
APPENDIX I: SCHEDULE OF STUDY VISITS AND EVALUATIONS .............................................................. 34 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF ABBREVIATIONS AND ACRONYMS 
 
AE 
 
 
Adverse Event 
ALT 
 
 
Alanine tranaminase 
AST 
 
 
Aspartate transaminase 
CBC 
 
 
Complete blood count 
CMP  
 
Comprehensive metabolic profile 
DNA   
 
Deoxyribonucleic acid 
DSMB   
 
Data and Safety Monitoring Board 
EAE   
 
Expedited adverse event 
FDA   
 
Food and Drug Administration 
GCLP   
 
Good Clinical Laboratory Practices 
GCP   
 
Good Clinical Practices 
Hep A total Ab  
Hepatitis A total antibody 
HBcAb  
 
Hepatitis B core antibody 
HBsAb  
 
Hepatitis B surface antibody 
HBsAg  
 
Hepatitis B surface antigen 
HCV 
 
 
Hepatitis C Virus 
HIV  
 
 
Human immunodeficiency virus 
INR 
 
 
International normalized ratio 
IoR  
 
 
Investigator of Record 
IRB  
 
 
Institutional Review Board 
ISR  
 
 
Interim Study Review 
mL  
 
 
Milliliter 
MWH  
 
Magee-Womens Hospital 
NIH  
 
 
National Institutes of Health 
OHRP   
 
Office of Human Research Protections 
OUD  
 
Opioid Use Disorder 
PHI 
 
 
Protected Health Information 
PI 
 
 
Principal Investigator 
PK 
 
 
Pharmacokinetics 
PoR 
 
 
Pharmacist of Record 
PPM 
 
 
Postpartum 
PRC 
 
 
Pregnancy Recovery Center 
PTID   
 
Participant identification number 
QOL 
 
 
Quality of life 
RNA   
 
Ribonucleic acid 
SAE   
 
Serious adverse event 
SOF 
 
 
Sofosbuvir 
SOF/VEL FDC 
Sofosbuvir/velpatasvir fixed-dose combination 
SOP   
 
Standard operating procedure(s) 
SSP   
 
Study-specific Procedures 
SVR 
 
 
Sustained virologic response 
UPMC  
 
University of Pittsburgh Medical Center 
VEL 
 
 
Velpatasvir 
 
 


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RESEARCH TEAM  
 
Principal Investigator:  
Elizabeth E. Krans, MD, Msc 
 
 
Department of Obstetrics, Gynecology, Reproductive Sciences, Magee-Womens Hospital 
 
 
300 Halket Street 
 
 
Pittsburgh PA 15213 
 
 
Phone: 412-641-4222 
 
 
Email: kransee@mail.magee.edu 
 
Co-investigator:  
Naudia Jonassaint, MD 
 
 
 
Thomas E. Starzl Transplantation Institute, UPMC Montefiore N758 
 
 
 
3459 Fifth Avenue  
 
 
 
Pittsburgh , PA 15213 
 
 
 
Phone: 412-864-5458 
 
 
 
Email: jonassaintnl@upmc.edu 
 
 
Co-investigator:  
Debra Bogen, MD 
 
 
Department of Pediatrics 
 
 
Children’s Hospital of Pittsburgh, 3414 Fifth Ave #1 
 
 
Pittsburgh PA 15213 
 
 
Phone: 412-692-5135  
 
 
Email: bogendl@upmc.edu 
 
Co-investigator:  
Jennifer Kiser, PharmD 
 
 
 
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado 
12850 E. Montview Blvd. V20-4102  
Aurora, CO 80045 
Phone: 303-724-6132  
Email: jennifer.Kiser@ucdenver.edu 
 
Co-investigator:  
Catherine Chappell, MD, MSc 
Magee-Womens Hospital of UPMC 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-1809 
Email: chappellca@upmc.edu 
 
Study Coordinator:  
Hollis Laird, MPH 
 
 
 
Magee Womens Research Institute 
 
 
 
3380 Boulevard of the Allies 
 
 
 
Pittsburgh PA 15213 
 
 
 
412-641-2248 
 
 
 
Email: lairdh2@mwri.magee.edu 
SUMMARY 
Short Title: 
Chronic Hepatitis C treatment with Sofosbuvir/Velpatasvir for postpartum women with 
OUD  
Clinical Phase: 
Phase IV 


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IND Sponsor: 
Exempt 
Protocol Chair: 
Elizabeth Krans, MD, MSc 
Sample Size: 
30 
Study Population: 
Postpartum women, a) chronic hepatitis C infection, b) 18 years or older  
Study Site: 
Magee-Womens Hospital of UPMC, Pittsburgh, PA 
Study Design: 
Single-site, single-arm prospective study 
Study Duration: 
2.5 years: 1 year for planned accrual + 1.5 year for postpartum follow-up 
Study Medication: 
Fixed-dose combination tablet of 400 mg of Sofosbuvir and 100 mg of Velpatasvir 
(SOF/VEL) 
Study Regimen:  
Participants will take SOF/VEL one tablet once daily starting within their first 12 months 
postpartum for 12 weeks total. 
Primary Objective: 
 
Evaluate the feasibility/acceptability of a combined, peripartum HCV and opioid maintenance treatment 
clinical protocol on adherence to HCV treatment regimens 
Primary Endpoint: 
 
Treatment feasibility will be established through the successful recruitment and enrollment of 
participants, administration of sofosbuvir/velpatasvir in the postpartum period and ability to determine 
SVR at 3 months following treatment completion.  
 
Acceptability of sofosbuvir/velpatasvir will be evaluated by self-report of treatment side effects and 
barriers and facilitators to treatment adherence.  
 
Adherence to sofosbuvir/velpatasvir will be evaluated with medication diaries, an assessment of missed 
doses, pill counts and attendance at opioid maintenance treatment visits. 
 
Secondary Objectives: 
 
To investigate SOF/VEL drug levels in breast milk. 
 
Evaluate the rate of IVDU recidivism, HCV reinfection and health related QOL in women with OUD 
during the first postpartum year.  
 
Secondary Endpoints: 
 
Breast milk concentrations of SOF, the SOF metabolite GS-331007 and VEL 
 
Rates of IVDU recidivism 
 
HCV reinfection 
 
Patient centered outcomes such as health related QOL will be assessed at 6, 9 and 12 months 
following treatment completion 
Table 1: Study Visit Schedule 
 
Study Visit 
Time Period* 
V1 
Screening A 
6 weeks 0 days to 12 months PPM 
V2 
Screening B 
6weeks 0 days to 12 months PPM 


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*These are target windows. If the participant cannot be seen within these windows then it will not be 
considered a protocol deviation 
**Start SOF/VEL and continue for 12 weeks 
***For a subset of participants, n=5 
 
 
V3 
Enrollment 
6 weeks 0 days to 12 months PPM 
V4** 
Treatment initiation 
1 day PPM – 12 months PPM   
VPK1-5*** 
Breastmilk PK visits 
2-10 days PPM 
V5 
2 week treatment follow-up 
14 days after treatment initiation 
V6 
4 week treatment  follow up 
28 days after treatment initiation 
V7 
6 week treatment  follow-up 
42 days after treatment initiation 
V8 
8 week  treatment follow-up 
56 days after treatment initiation 
V9 
10 week  treatment follow-up 
70 days after treatment initiation 
V10 
End of Treatment Visit 
12 weeks treatment follow-up 
84 days after treatment initiation 
V11 
SVR Visit 
3 months post-treatment follow-up 
6 months after treatment initiation 
V12 
9 months post-treatment follow-up 
12 months after treatment initiation 
V13 
End of Study 
15 months post-treatment follow up 
18 months after treatment initiation  


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KEY ROLES 
 
Protocol Identification 
 
Protocol Title:  
Management of HCV infection in pregnant and postpartum women with 
OUD: the potential of an integrated medical home model 
  
Short Title: 
 
Chronic Hepatitis C treatment with Sofosbuvir/Velpatasvir for postpartum 
women with OUD  
Date:  
 
 
May 10, 2017 
Funders, Sponsor and Monitor Identification 
 
Funding Agency:  
Gilead Sciences Investigator Initiated Studies Program 
Site Monitoring: 
Elizabeth Krans, MD MSc 
Pharmaceutical Collaborator: 
Gilead Sciences 
 
 
 
INTRODUCTION 
Background  
Intravenous drug use (IVDU) is the leading cause of new Hepatitis C virus (HCV) infections and is widespread 
among pregnant women with OUD. HCV screening during pregnancy is recommended for women with risk 
factors for HCV exposure and provides a unique opportunity to identify the virus among high-risk women of 
reproductive age. HCV positivity in pregnant women with OUD ranges from 40-75% and over 28% are newly 
diagnosed with HCV during pregnancy. Pregnancy is a unique opportunity to engage HCV-infected women in 
efforts to improve their health and facilitate HCV treatment. However, less than 2% of HCV-infected pregnant 
patients initiate HCV treatment within one year following delivery. 
Rationale 
Incorporating HCV treatment into opioid maintenance treatment program clinical protocols is an innovative 
health care delivery model that has been associated with improved HCV treatment uptake in non-pregnant, 
drug-using populations. This “medical home” approach would combine HCV and opioid maintenance treatment 
into one treatment regimen and incorporate the expertise of obstetricians, hepatologists, substance abuse 
treatment providers and pediatricians into one comprehensive clinical care model. We hypothesize that co-
locating prenatal care, HCV treatment and substance abuse treatment services in the same clinical 
environment will significantly improve HCV treatment uptake and compliance as well as facilitate ongoing 
recovery from opioid addiction. 
SOF/VEL Fixed Dose Combination 
Description 
The study medication is a fixed-dose combination tablet containing sofosbuvir and velpatasvir for oral 
administration. Sofosbuvir is a nucleotide analog HCV NS5B polymerase inhibitor and velpatasvir is an NS5A 
inhibitor. 


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Each tablet contains 400 mg sofosbuvir and 100 mg velpatasvir. The tablets include the following inactive 
ingredients: copovidone, croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 
tablets are film-coated with a coating material containing the following inactive ingredients: iron oxide red, 
polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. 
Sofosbuvir: The IUPAC name for sofosbuvir is (S)-Isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-
dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)-
(phenoxy)phosphorylamino)propanoate. It has a molecular formula of C22H29FN3O9P and a molecular weight 
of 529.45. Sofosbuvir is a white to off-white crystalline solid with a solubility of at least 2 mg/mL across the pH 
range of 2–7.7 at 37 oC and is slightly soluble in water. 
Velpatasvir: The IUPAC name for velpatasvir is Methyl {(1R)-2-[(2S,4S)-2-(5-{2-[(2S,5S)-1-{(2S)-2-
[(methoxycarbonyl)amino]-3-methylbutanoyl}-5-methylpyrrolidin-2-yl]-1,11-
dihydro[2]benzopyrano[4',3':6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-
yl]-2-oxo-1-phenylethyl}carbamate. It has a molecular formula of C49H54N8O8 and a molecular weight of 
883.0. Velpatasvir is practically insoluble (less than 0.1 mg/mL) above pH 5, slightly soluble (3.6 mg/mL) at pH 
2, and soluble (greater than 36 mg/mL) at pH 1.2. 
Mechanism of Action 
Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is required for viral 
replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form the 
pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by 
the NS5B polymerase and acts as a chain terminator. In a biochemical assay, GS-461203 inhibited the 
polymerase activity of the recombinant NS5B from HCV genotype 1b, 2a, 3a, and 4a with an IC50 value ranging 
from 0.36 to 3.3 micromolar. GS-461203 is neither an inhibitor of human DNA and RNA polymerases nor an 
inhibitor of mitochondrial RNA polymerase. Sofosbuvir has a very short half-life in plasma. SOF accounts for 
only ~4% of the drug related material circulating in plasma. The majority (>90%) of the drug-related material in 
plasma is in the form of GS-331007, an inactive metabolite of sofosbuvir.  
Velpatasvir is an inhibitor of the HCV NS5A protein, which is required for viral replication. Resistance selection 
in cell culture and cross-resistance studies indicate velpatasvir targets NS5A as its mode of action. 
Clinical Studies 
 
Clinical Studies of Sofosbuvir/Velpatasvir for the Treatment of HCV 
Approximately 1035 participants have been enrolled in several multicenter, Phase 3 trials to assess the efficacy 
of treatment with SOF/VEL in patients with genotype 1, 2, 3, 4, 5 and 6 chronic hepatitis C virus infection.   
 
 
 
 
 
 
 


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Table 2: Study ASTRAL-1: Virologic Outcomes by HCV Genotype in SOF/VEL Treated Subjects without 
Cirrhosis or with Compensated Cirrhosis (12 Weeks After Treatment) 
 
EPCLUSA 12 Weeks 
(N=624) 
Total 
(all GTs) 
(N=624) 
GT-1 
 
GT-2 
(N=104) 
 
GT-4 
(N=116) 
 
GT-5 
(N=35) 
 
GT-6 
(N=41) 
GT-1a 
(N=210) 
GT-1b 
(N=118) 
Total 
(N=328) 
SVR12 
99% 
(618/624)
98% 
(206/210)
99% 
(117/118)
98% 
(323/328)
100% 
(104/104)
100% 
(116/116)
97% 
(34/35) 
100% 
(41/41) 
Outcome for Subjects without SVR 
On-Treatment 
Virologic 
Failure
 
0/624 
 
0/210 
 
0/118 
 
0/328 
 
0/104 
 
0/116 
 
0/35 
 
0/41 
Relapsea 
<1% 
(2/623) 
<1% 
(1/209) 
1% 
(1/118) 
1% 
(2/327) 
0/104 
0/116 
0/35 
0/41 
Otherb 
1% 
(4/624) 
1% 
(3/210) 
0/118 
1% 
(3/328) 
0/104 
0/116 
3% 
(1/35) 
0/41 
GT = genotype; no subjects in the placebo group achieved SVR12. 
a. 
The denominator for relapse is the number of subjects with HCV RNA <LLOQ at their last on-treatment assessment 
b. 
Other includes subjects who did not achieve SVR and did not meet virologic failure criteria. 
 
Table 3: Study ASTRAL-3: Virologic Outcomes in Subjects with Genotype 3 HCV without Cirrhosis or 
with Compensated Cirrhosis (12 Weeks After Treatment) 
 
EPCLUSA 12 Weeks 
(N=277) 
SOF + RBV 24 Weeks 
(N=275) 
SVR12 
95% (264/277) 
80% (221/275) 
 
Treatment difference +14.8%; 
95% confidence interval (+9.6% to +20.0%) 
Outcome for subjects without SVR 
On-Treatment Virologic Failure 
0/277 
<1% (1/275) 
Relapsea 
4% (11/276) 
14% (38/272) 
Otherb 
1% (2/277) 
5% (15/275) 
SOF = sofosbuvir; RBV = ribavirin. 
a. 
The denominator for relapse is the number of subjects with HCV RNA <LLOQ at the last on-treatment assessment 
b. 
Other includes subjects who did not achieve SVR and did not meet virologic failure criteria. 
Safety  
 
The adverse reactions data for SOF/VEL in patients without cirrhosis or with compensated cirrhosis were derived 
from three Phase 3 clinical trials (ASTRAL-1, ASTRAL-2, and ASTRAL-3) which evaluated a total of 1035 
subjects infected with genotype 1, 2, 3, 4, 5, or 6 HCV, without cirrhosis or with compensated cirrhosis, who 
received SOF/VEL for 12 weeks. SOF/VEL was studied in placebo- and active-controlled trials. The proportion 
of subjects who permanently discontinued treatment due to adverse events was 0.2% for subjects who received 
SOF/VEL for 12 weeks. The most common adverse reactions (adverse events assessed as causally related by 
the investigator and at least 10%) were headache and fatigue in subjects treated with SOF/VEL for 12 weeks. 


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Adverse reactions, all grades, observed in greater than or equal to 5% of subjects receiving 12 weeks of 
treatment with SOF/VEL in ASTRAL-1 include headache (22%), fatigue (15%), nausea (9%), asthenia (5%), and 
insomnia (5%). Of subjects receiving SOF/VEL who experienced these adverse reactions, 79% had an adverse 
reaction of mild severity (Grade 1). With the exception of asthenia, each of these adverse reactions occurred at 
a similar frequency or more frequently in subjects treated with placebo compared to subjects treated with 
SOF/VEL (asthenia: 3% versus 5% for the placebo and SOF/VEL groups, respectively). The adverse reactions 
observed in subjects treated with SOF/VEL in ASTRAL-2 and ASTRAL-3 were consistent with those observed 
in ASTRAL-1. Irritability was also observed in greater than or equal to 5% of subjects treated with SOF/VEL in 
ASTRAL-3. 
Rationale for Study Design 
Incorporating HCV treatment into opioid maintenance treatment program clinical protocols is an innovative health 
care delivery model that has been associated with improved HCV treatment uptake in non-pregnant, drug-using 
populations. This “medical home” approach would combine HCV and opioid maintenance treatment into one 
treatment regimen and incorporate the expertise of obstetricians, hepatologists, substance abuse treatment 
providers and pediatricians into one comprehensive clinical care model. 
OBJECTIVES  
Primary Objective 
1. To evaluate the feasibility/acceptability of a combined, peripartum HCV and opioid maintenance 
treatment program on adherence to HCV treatment regimens. 
Secondary Objectives 
1. To investigate SOF/VEL drug levels in breast milk.  
2. Evaluate the rate of IVDU recidivism, HCV reinfection and health related QOL in women with OUD 
during the first postpartum year.  
STUDY DESIGN 
Identification of Study Design 
This is a single-site, open label, single-arm Phase IV trial.  
Summary of Major Endpoints 
Primary Endpoints: 
 
Treatment Feasibility 
- 
Successful recruitment and enrollment of participants 
- 
Administration of SOF/VEL in the postpartum period 
- 
Ability to determine SVR at 3 months following treatment 
 
Acceptability 
- 
Self-report of treatment side effects 
- 
Self-report of barriers and facilitators to treatment adherence 
 
Adherence 
- 
Medication diaries 
- 
Assessment of missed doses  


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- 
Pill counts 
- 
Attendance at opioid maintenance treatment visits 
Secondary Endpoints:  
- 
Breast milk concentrations of SOF, GS-331007, and VEL 
- 
Rates of IVDU recidivism 
- 
HCV reinfection 
- 
Patient centered outcomes such as health related QOL will be assessed at 6, 9 and 12 months 
following treatment completion 
- 
Pregnancy and delivery outcomes collected prospectively by chart review and participant interview 
Description of Study Population 
The study population will include 30 pregnant and postpartum women between the ages of 18-39 year old 
(inclusive) at screening who are chronically infected with Hepatitis C virus, as described in Sections 5.2 and 5.3.  
Time to Complete Accrual 
The approximate time to complete study enrollment is expected to be 12 months.  
Expected Duration of Participation 
The expected duration for maternal and infant participants is approximately 18 months after SVR Assessment, 
not including the screening window. Maternal study data will be collected from the participant and/or her medical 
records through the End of Study Visit (15 month post-treatment visit, V14). Infant study data will be collected 
from his/her medical record after End of Study Visit (15 month post-treatment visit, V14).  
STUDY POPULATION 
Selection of the Study Population 
The inclusion and exclusion criteria in Sections 5.2 and 5.3 will be utilized to ensure the appropriate selection of 
study participants. 
Recruitment 
HCV-infected pregnant or postpartum women will be recruited from the outpatient obstetrical clinics at Magee-
Womens Hospital (MWH) of UPMC. There are over 10,000 deliveries at MWH per year and it is estimated that 
approximately 1% of women who deliver are infected with HCV.  Recruitment will be primarily targeted from the 
MWH Pregnancy Recovery Center, which was established in 2014 to provide concurrent treatment for OUD 
with prenatal care, which has an estimated retention rate of 90% for weekly opiate substitution and prenatal 
visits.  There are approximately 120 pregnant women with OUD who receive prenatal care at the Pregnancy 
Recovery Center per year.  The prevalence of HCV infection in this Center is approximately 60%.  Recruitment 
materials will be approved by the University of Pittsburgh Institutional Review Board prior to use. 
Retention 
The importance of retention will be stressed to the participant at each visit as part of protocol adherence 
counseling.  Once a participant is enrolled, the study staff will make every effort to retain the participants in 
follow-up to minimize possible bias associated with loss-to-follow-up.     
Inclusion Criteria 


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Women must meet all of the following criteria to be eligible for inclusion in the study. Any exclusionary laboratory 
values can be repeated at a later date within the screening window.  If the repeated laboratory values meet 
inclusion criteria then the participant can be enrolled. If there is concern that the participant’s health status has 
changed between the enrollment visit and the screening visit or if there is concern by the study investigators that 
the participant might not remain eligible, the screening laboratories can be repeated prior to enrollment.   
1) 
Age 18 or older 
2) 
Able and willing to provide written informed consent to be screened for and take part in the study 
procedures 
3) 
Able and willing to provide adequate contact information 
4) 
Chronic HCV, genotype 1 (1a, 1b), 2 (2a, 2b), 3, 4, 5, 6 infection, defined as a HCV antibody and 
detectable HCV RNA viral load at screening 
5) 
Pregnancy at 6 + 0 to gestation to 12 months PPM at screening B  
6) 
Documented negative Hepatitis B testing within 3 months prior to enrollment  
7) 
Negative HIV testing within 3 months prior to enrollment or documented immunity to Hepatitis B as a 
result of vaccination 
8) 
Per participant report at screening and enrollment, agrees not to participate in other research studies 
involving drugs or medical devices for the duration of study participation 
9) 
Plans to deliver at Magee-Womens Hospital of UPMC (if being recruited during pregnancy) 
10)  Willing to obtain a Nexplanon, IUD, or Depo Provera shot for treatment duration (12 weeks) or has a 
planned tubal ligation 
Exclusion Criteria 
Women who meet any of the following criteria will be excluded from the study: 
1) 
Participant report of any of the following at Screening or Enrollment: 
a. Previous treatment for Hepatitis C virus with a sofosbuvir based regimen 
b. Use of any medications contraindicated with concurrent use of sofosbuvir/velpatasvir according 
to the EPCLUSA package insert1 
c. Plans to relocate away from the study site area in the next 18 months 
d. Current sexual partner is known to be infected with HIV or Hepatitis B virus 
e. History of decompensated cirrhosis (history of variceal bleed, ascites or hepatic 
encephalopathy) 
2) 
Reports participating in any other research study involving drugs or medical devices within 60 days or 
less prior to enrollment 
3) 
Breastfeeding or feeding infant expressed breastmilk at the time of treatment initiation (Women who 
participate in the breastmilk PK portion of the study (n=5) will express breastmilk exclusively for 
participation in the research study) 
4) 
Any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, 
gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease (other 
than Hepatitis C) 
5) 
Has any of the following laboratory abnormalities: 
a. Aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 10 times the 
upper limited of normal at screening 
b. Hemoglobin less than 10 g/dL immediately prior to treatment initiation 
c. Platelet count less than 90,000 per mm3 immediately prior to treatment initiation 
d. International normalized ratio (INR) > 1.5  
e. GFR < 40  


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6) 
Has any other condition that, in the opinion of the IoR/designee, would preclude informed consent, 
make study participation unsafe, complicate interpretation of study outcome data, or otherwise 
interfere with achieving study objectives. 
STUDY MEDICATION 
Regimen 
Each participant will take a 12 week course of SOF/VEL one tablet by mouth, once daily.   
Administration 
Study medication will be dispensed in the immediate postpartum period in the quantities sufficient to have one 
dose per day until the next scheduled visit with 2 extra doses. Tablets will be packaged by the Investigational 
Pharmacist/Pharmacist of Record (PoR) in the pharmacy at Magee-Womens Hospital.   Participants will be given 
a medication administration log to assist them with keeping track of when they took their doses. The medication 
administration log will include instructions on timing of the dose, what to do if a dose is missed and how to store 
the medication. If a dose is missed, they should take the dose as soon as it is remembered, but only one dose 
per day.  Participants will be instructed to take their medication in the morning each day at the same time, 
preferably early in the morning.  SOF/VEL can be taken with or without food.  Additionally, participants will be 
given adherence tips, such as setting an alarm on their phone, linking medication taking to another daily activity, 
etc. Participants will be instructed to bring any unused medication to their next visit.  Participants will be instructed 
to call the study staff immediately if they run out of medication or if they lose their study medication.  In this case, 
all possible efforts will be made to get the participant study medication as soon as possible. 
Supply and Accountability 
 
Supply 
Gilead Sciences will manufacture the study medication under Good Manufacturing Practices (GMP) and will 
package, label and ship all of the study medication directly to the PoR at Magee-Womens Hospital. 
Storage and Dispensing 
SOF/VEL should be stored at room temperature below 30°C within the main pharmacy at Magee-Womens 
Hospital1. The PoR will maintain documentation of temperature in the area where the study medication is stored. 
Study medications will be dispensed from the pharmacy in a small bottle until the next study visit with two 
additional doses in the case of a lost dose or missed study visit.  Study medications will be dispensed from the 
pharmacy only upon receipt of a written prescription from an authorized prescriber.  The study medication will 
be dispensed to the study staff, then subsequently provided directly to the study participant in the research clinic.  
Accountability 
The PoR will maintain complete accountability records of all study SOF/VEL FDC received and dispensed. All 
unused study medications will be returned to Gilead Sciences after the study is complete.  
Retrieval of Study Medication 
The participants will be instructed to return any unused medication at each visit. If the participant fails to return 
unused medication at a scheduled visit, alternate arrangements will be made to obtain the unused medication 
from the participant (i.e. at an unscheduled visit). Unused medication will be accounted for by the clinician, 
documented in the participant’s research record and then returned to the PoR.  
Concomitant Medications  


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Enrolled study participants may use non-prohibited concomitant medications during study participation. All 
concomitant medications reported throughout the course of the study will be recorded on case report forms 
designated for that purpose. All prescription medications and over-the-counter preparations including vitamins 
will be recorded on forms for concomitant medications. Participants will be prohibited from using nutritional 
supplements, herbal preparations and medications contraindicated for concomitant use with Sofosbuvir and 
Velpatasvir as described in the package insert. Each reported medication will be reviewed to ensure the 
participant is not using prohibited medications as referenced in the Epclusa package insert. At each visit, 
participants will be asked if they have initiated any new medications or changed any reported medications. If the 
participant reports using acid suppressing medications, specific dosing instructions will be reviewed regarding 
correct timing of acid suppressing medication use according to the Epclusa package insert.   
STUDY PROCEDURES 
An overview of the study visit and evaluations schedule is presented in Appendix 1. Any clinical or laboratory 
information collected as a part of the participant’s routine clinical care occurring on the same day as the study 
visit does not need to be repeated and can be collected from the participant’s medical record.   
Pre-screening 
With IRB approval, study staff will pre-screen records to identify potential participants by evaluating minimum 
criteria (i.e. age, gestational age, Hepatitis C status).  Clinic staff will be informed of the study and will be asked 
to provide an IRB-approved material to potential participants or will assess interest.  If the participant agrees, 
research staff can provide additional information by reviewing an IRB-approved screening script, which will 
include a brief overview of the study and minimum eligibility questions.  Women who are interested and qualify 
based on the screening script may schedule a screening visit if interested.  Process information (e.g., number of 
potential participants contacted, number presumptively eligible) may be recorded and stored at the study site in 
the absence of written informed consent from potential participants, provided the information is collected in such 
a manner that it cannot be linked to participant identifiers. Procedures and documentation will comply with the 
University of Pittsburgh IRB requirements. IRB approved ads and flyers may also be used (i.e. hung throughout 
the hospital; displayed on electronic boards; emailed to providers or appropriate support or community groups). 
Visit 1- Screening A (V1) 
Screening Visit A can take place anytime with the screening window. Multiple visits may be conducted to 
complete all required screening procedures, if necessary. Written informed consent will be obtained before any 
screening procedures are initiated. All participants will meet with hepatology who will ultimately determine 
whether to initiate hepatitis C treatment in the immediate postpartum period and participants will be encouraged 
to discuss participation in the study with hepatology. For participants who subsequently do not meet the eligibility 
criteria, screening will be discontinued once ineligibility is determined. Any exclusionary laboratory values can 
be repeated at a later date within the screening window. If the repeated laboratory values meet inclusion criteria 
then the participant can be enrolled. If there is concern that the participant’s health status has changed between 
the enrollment visit and the screening visit or if there is concern by the study investigators that the participant 
might not remain eligible, the screening laboratories can be repeated prior to enrollment. 
 
 
 
 
 


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Table 4: Screening Visit A (V1) 
Visit 1- Screening Visit A 
Component 
Procedures 
Administrative and Regulatory 
 
 
Review and obtain written informed consent for screening 
 
Sign appropriate medical record releases (i.e. to obtain records from 
the Pregnancy Recovery Center; outside records as necessary) 
 
Collect contact information 
 
Screening Questionnaire 
 
Assess eligibility  
 
Provide reimbursement for screening visit 
 
Schedule next visit  
Clinical 
 
Collect medical history & review medical/prenatal records including 
documentation of chronic Hepatitis C, Opioid Use Disorder and 
gestational age/dating 
Laboratory 
 
Collect blood 
 
HCV antibody* 
 
HCV RNA* 
 
HBsAg* 
 
HIV* 
*If not already available in the medical record 6 months prior to Screening A visit or not anticipated to be obtained by their primary 
health care provider prior to enrollment 
Visit 2- Screening B (V2) 
The following procedures will occur at the Screening B visit.  Screening Visit B can take place anytime with the 
screening window. All patients who meet basic eligibility criteria [chronic HCV, OUD, HIV negative, appropriate 
GA] will meet with Hepatology, who will conduct a full medical history and physical exam and ultimately 
determine if the patient is eligible to participate in the study. Participants will also complete the baseline 
assessment at this visit.  
Table 5: Screening Visit B (V2) 
Visit 2- Screening Visit B 
Component 
Procedures 
Administrative and Regulatory 
 
 
Review written informed consent for screening 
 
Review/update locator information 
 
Overview of study procedures/treatment regimen if participant 
chooses to enroll 
 
Schedule next visit (Enrollment visit with hepatology) if 
appropriate 
 
Complete Baseline Questionnaire  
Clinical 
 
Collect medical history & review medical/prenatal records including 
documentation of chronic Hepatitis C and gestational age/dating 
 
Review of concomitant medications 
 
 
Laboratory** 
Collect blood 
 
HCV genotype* 
 
HepBcAb* 
 
HepBsAb* 
 
HepB DNA (only if surface antigen and core Ab positive)* 
 
HepA total antibody* 
 
PT/INR 
 
CMP* 


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*If not already available in the medical record 6 months prior to Screening B visit or not anticipated to be obtained by their primary 
health care provider prior to enrollment 
** Please note, if treatment initiation (V4) is occurring within 3 months of Screening B (V2), treatment initiation labs can be drawn at V2 
 
Enrollment (V3) 
The following procedures will occur at the Enrollment visit (V3). The Enrollment Visit may occur between 6+0 
weeks gestational age and 12 months  postpartum. During the enrollment visit the participant will meet with the 
hepatologist, and sign the informed consent form. 
Table 6: Enrollment (V3) 
Enrollment Visit- Visit 3 (V3) 
Component 
Procedures 
Administrative and Regulatory 
 
 
Confirm eligibility 
 
Review/update locator information 
 
Review and obtain written informed consent for treatment 
 
ICF Comprehension Assessment 
 
Assign participant ID (PTID) 
 
Schedule next visit 
Clinical 
 
Review/update medical history, review medical record, document pre-
existing conditions 
 
Instruct participants to contact study staff when in labor/being 
admitted to MWH labor and delivery if appropriate 
 
Provide Screening test results 
 
Review of concomitant medications 
 
Consultation with hepatologist 
 
Physical exam 
Laboratory 
 
None 
Treatment Initiation (V4) 
The treatment initiation visit will occur in the immediate postpartum period (1-14 days postpartum) or 
within 12 months postpartum if breastfeeding. Please note, if treatment initiation (V4) is occurring 
within 3 months of Screening B (V2), treatment initiation labs can be drawn at V2. During the treatment 
initiation visit the participant will be given instructions on using and begin taking the study 
medication.Table 7: Treatment Initiation (V4) 


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Treatment Initiation Visit- Visit 4 (V4) 
Component 
Procedures 
Administrative and Regulatory 
 
 
Confirm eligibility 
 
Review/update locator information 
 
Sign appropriate infant medical record releases 
 
Completed visit questionnaire 
 
Schedule next visit 
Behavioral 
 
Provide counseling  
 
Protocol adherence 
 
Study medication use/adherence 
Clinical 
 
Review/update medical history 
 
Review/update concomitant medications 
 
Provide contraceptive counseling 
 
Provide available test results 
 
Obtain urine pregnancy test 
Medications 
 
Participants will receive study medication (supply enough for next visit 
plus 2 extra doses) 
 
Participants will receive instructions for medication use 
 
Participants will receive medication adherence log 
Laboratory 
 
CMP* 
 
CBC* 
 
GGT* 
 
 
*If not already available in the medical record 3 months prior to Treatment Initiation Visit  
Breastmilk Pharmacokinetics Substudy 
A subset of women (n=5) will participate in a sub-study to determine the quantity of drugs (SOF and VEL) 
transferred into breastmilk. Because the drug has not been studied in infants, all expressed milk will be 
maintained by the study. We ask each of the 5women to express 5 samples of breastmilk and have paired 
blood samples collected at their convenience. Samples will be obtained starting at least 6 hours after the first 
dose and no sooner than 6 hours from a previous sample. All samples will be obtained by day 10 postpartum. 
The time of prior SOF/VEL dosing will be carefully recorded as well as the time of the breastmilk and blood 
collection.   
Participants will be instructed to take their daily dose at home as usual. This subsample of participants will be 
given a pill box (Wisepill) that tracks drug timing so that we have accurate time stamp for when the drug was 
taken. This is important for the PK study to ensure women were adherent with the medication and to track the 
time of prior doses in relation to milk and blood collection.  
Women will be asked to only express milk when they are at Magee-Womens Hospital under the supervision of 
the study staff. Women will be asked to express until both breasts are soft and the milk expression rate slows. 
Because women will be pumping infrequently, their milk volume will diminish and by 10 days, will be of limited 
volume. Individual venipuncture(s) will be used to collect all plasma samples, and participants will be instructed 
on how to pump to obtain breastmilk samples.  
Case report forms will be completed for each set of breastmilk and blood samples obtained. Two 5-mL 
breastmilk samples will be processed and stored. One 5-mL aliquot of whole intact milk will be transferred to a 
cyrovial and stored. The second 5-mL aliquot will be centrifuged, the lipid layer removed and transferred to a 
cryovial and the remaining fluid transferred to a separate cryovial. All three cryovials will be stored at -
80°Celcius until shipment to the Colorado Antiviral Pharmacology Laboratory for analysis. 5-mL of blood will be 


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obtained in a K2 EDTA tube and centrifuged, the plasma transferred to a cryovial and stored at -80°Celcius 
until shipment to the Colorado Antiviral Pharmacology Laboratory.  
SOF, the SOF metabolite GS-331007 and VEL will be measured in plasma and breastmilk using validated 
LC/MS-MS methods at the Colorado Antiviral Pharmacology Laboratory.  
Table 8: Breastmilk Pharmacokinetics Visits (PK1-5) 
Breastmilk Pharmacokinetics Visits (PK1-5) 
Component 
Procedures 
Administrative and Regulatory 
 
 
Review/update locator information 
 
Visit questionnaire  
 
Provide reimbursement for study visit 
 
Record/update AEs 
 
Schedule next visit 
Behavioral 
 
Adherence assessment  
 
Provide modified counseling  
 
Protocol adherence 
 
Study medication use/adherence 
Clinical 
 
Administer timed dose of study medication 
 
Adherence assessment 
Laboratory 
 
Collect blood (all visits) 
 
Collect breastmilk sample (all visits) 
 
Follow up postpartum visits (Visits 5-9)  
1) 2 week treatment follow-up (V5): 14 days after treatment initiation 
2) 4 week treatment follow-up (V6): 28 days after treatment initiation 
3) 6 week treatment follow-up (V7): 42 days after treatment initiation 
4) 8 week treatment follow-up (V8): 56 days after treatment initiation 10 week treatment follow-up (V9): 70 
days after treatment initiation 
The follow up visits will be scheduled as early as possible within the window to allow for visits that require 
rescheduling. 
Table 9: Postpartum Follow-up Visits (V5-9) 
Postpartum Follow-up Visits 5-9 (V5-9) 
Component 
Procedures 
Administrative and Regulatory 
 
 
Review/update locator information 
 
Visit questionnaire  
 
Record/update AEs 
 
Schedule next visit 
Behavioral 
 
Provide modified counseling  
 
Protocol adherence 
 
Study medication use/adherence 
Clinical 
 
Review/update medical history 
 
Review/update concomitant medications 
 
Provide study medication with sufficient supply until next visit with 3 
additional doses 
 
 Provide test results if available 
 
Obtain urine pregnancy test (V7 only) 


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Laboratory* 
Varies by visit: 
 
Visit 6 (4 week postpartum follow up) 
o 
HCV RNA 
o 
CMP, CBC, GGT 
 
Visit 8 (8 week postpartum follow up) 
o 
CMP, CBC, GGT 
 
All other visits: None 
*If necessary, V6 labs can be drawn at V7 and V8 labs can be drawn at V9 
End of Treatment Visit (12 week treatment follow-up, V10) 
The following procedures will occur at the End of Treatment visit.  This visit will be scheduled within 7 days of 
completion of the 12 week course of study medication.  The purpose of this visit will be to collect any remaining 
study medication and to collect and follow up on any adverse events.   
Table 10:  End of Treatment Visit 
End of Treatment Visit (12 week postpartum follow-up, V10) 
Component 
Procedures 
Administrative and Regulatory 
 
 
Review/update locator information 
 
Visit Questionnaire 
 
Record/update AEs  
 
Schedule next visit 
Behavioral 
 
Collect remaining study medication and medication administration log 
 
Conduct qualitative interview 
Clinical 
 
 
Review/update medical history 
 
Review/update concomitant medications 
 
Consultation with hepatologist (only if HCV virus not cleared at 8w) 
 
Provide test results if available  
Laboratory 
 
HCV RNA 
 
CMP, CBC, GGT 
 
SVR Assessment (3 month post-treatment visit, V11) 
The following procedures will occur at the 3 month post-treatment visit  
Table 11: SVR Assessment  (V11) 
SVR Assessment (3 month post-treatment visit, V11)  
Component 
Procedures 
Administrative and Regulatory 
 
 
Review/update locator information 
 
Visit Questionnaire 
 
Record/update AEs  
 
Schedule next visit  
 
Conduct qualitative interview 
Clinical 
 
 
Review/update medical history 
 
Provide test results if available  
 
Consultation with hepatologist (by phone) 
Laboratory 
 
HCV RNA  
 
CMP, CBC, GGT 
 
9 month post-treatment visit (V12) 


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The following procedures will occur at the 9 month post-treatment visit (V13) 
Table 13: 9 month post-treatment visit (V12) 
V13: 9 month post-treatment visit 
Component 
Procedures 
Administrative and Regulatory 
 
 
Review/update locator information 
 
Review infant demographics/sign release(s) for medical records for 
infant (if necessary) 
 
Schedule next visit  
Clinical
 
 
Review/update medical history 
 
Provide available test results  
Laboratory 
 
 
HCV RNA 
 
CMP, CBC, GGT 
 
End of Study Visit (15 month post-treatment visit, V13)  
The following procedures will occur at the End of Study visit (V14). If the participant is unable/unwilling to 
return to MWH, this visit may be conducted via phone and/or email. 
Table 14: End of Study visit (V13) 
V14: End of Study Visit 
Component 
Procedures 
Administrative and Regulatory 
 
 
Review results of infant HCV testing/sign release(s) for medical 
records for infant (if necessary) 
 
 
Clinical
 
 
Review/update medical history 
 
Provide available test results  
Laboratory 
 
 
None 
 
Follow-up Procedures for Participants Who Permanently Discontinue Study Medication 
Participants will be permanently discontinued for significant laboratory abnormalities or adverse events as 
outlined in section 9.3 and 9.4 or if they choose to discontinue the study medication.  Participants who are 
permanently discontinued from the study will be instructed to return the study medication and study medication 
log. All protocol-specified study procedures will continue for safety except the following: 
 
Provision of study medication 
 
Provision of medication use adherence counseling  
The following procedures will be performed at the visit in which study medication use is permanently 
discontinued: 
 
Viral load as needed (i.e. participant withdraws, investigator opinion) 
The participant will be asked to continue in the study and complete all remaining scheduled maternal and infant 
visits per protocol for safety.  
Interim Visits 


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Interim visits may be performed at any time during the study. Study procedures may be repeated at interim visits 
as deemed clinically indicated.  All interim contacts and visits will be documented in participants' study records 
and on applicable CRFs.  
Adherence Counseling and Assessment 
Adherence counseling to the study protocol will be performed at each study visit.   Additionally, investigators 
may use text messaging (daily or weekly), follow-up phone calls and meeting study participants at their regular 
clinic visits in order to improve adherence the study medication.  All options will be included in the informed 
consent document and will be tailored to the participant’s needs.  At the follow-up visits (V5-10) all remaining 
medication will be counted, recorded and returned to the pharmacy.  Study participants will be given a medication 
administration log upon enrollment to assist in study medication adherence.  Each log will have instructions on 
how and when to take the medication. We will recommend that participants take the study medication between 
8:00am and 9:00am daily.  If a participant forgets to take a dose, she should take the missed dose as soon as 
she remembers but should never take more than one tablet of SOF/VEL FDC per day.  Directions on how to 
store the medication as well as what to do if the medication is lost or stolen will be included on the medication 
administration log.  Participants will be asked to bring the medication administration log to the next study visit for 
review.  Medication administration logs will be collected and a new log will be given with each bottle/refill of study 
medication.  
In Depth Interviews and Qualitative Analysis 
At the End of Treatment visit (V10) and End of Study visit (V14) a trained interviewer will conduct an in depth 
qualitative interview about Hepatitis C infection, HCV transmission risk behaviors, and HCV treatment during 
the postpartum period. All interviews will be recorded and transcribed verbatim.  The original recordings will be 
destroyed after transcription.  Following transcription, the research team will develop a qualitative codebook 
using an editing approach to ensure that all relevant topics and themes are represented. Two trained 
qualitative coders will then be trained in the codebook. Coding will be completed using Atlas.ti software, which 
will help to determine the frequency and prevalence of the topics and themes which were discussed. Thematic 
analysis will then be completed using a constant comparative method. 
Clinical Evaluations and Procedures 
Physical exams will include the following assessments:  
 
General appearance 
 
Weight  
 
Vital signs 
 
Temperature 
 
Pulse  
 
Blood pressure 
 
Respirations 
 
Height * 
 
Abdomen*  
 
Head, Eye, Ear, Nose and Throat (HEENT) Examination* 
 
Lymph nodes*  
 
Neck*  
 
Heart* 
 
Lungs*  
 
Extremities* 


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 
Skin*  
 
Neurological* 
 
*may be omitted after the Enrollment Visit 
 
Additional clinical assessments may be performed at the discretion of the examining clinician in response to 
symptoms or illnesses present at the time of the exam. 
 
Laboratory Evaluations 
UPMC’s Clinical Laboratory will be used for HCV treatment laboratory evaluations: 
 
Blood 
o HCV antibody 
o HCV RNA viral load 
o Hepatitis C genotype  
o HIV 
o HepBsAg, HepBcAb, HepBsAb 
o HepB DNA 
o HepA total Ab 
o CBC with differential and platelets 
o CMP  
o GGT 
Colorado Antiviral Pharmacology Laboratory: 
o PK blood testing 
o Breastmilk 
 
Specimen Collection and Processing 
The study site will adhere to the standards of good clinical laboratory practice and standard operating 
procedures for proper collection, processing, labeling, transport, and storage of specimens. Specimens for 
SOF/VEL PK analysis will be transported from the Clinical Research site to Magee-Womens Research Institute 
for storage until they are shipped to the appropriate laboratory for processing and analysis.  The samples will 
be shipped when arranged with the respective laboratories listed for PK analysis. 
Biohazard Containment 
As the transmission of hepatitis C and other blood-borne pathogens can occur through contact with contaminated 
needles, blood, and blood medications, appropriate blood and secretion precautions will be employed by all 
personnel during blood draws and handling of all specimens for this study as recommended by the CDC and 
National Institutes of Health (NIH). All biological specimens will be shipped using packaging mandated by Code 
of Federal Regulations (CFR) 42 Part 72. All dangerous goods materials, including diagnostic specimens and 
infectious substances, must be shipped according to instructions detailed in the International Air Transport 
Association (IATA) Dangerous Goods Regulations. Biohazardous waste will be contained according to 
institutional, transportation/carrier, and all other applicable regulations.   
 
ASSESSMENT OF SAFETY 


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Safety Monitoring 
The Principal Investigator (PI, Dr. Krans) is responsible for continuous close safety monitoring of all study 
participants, and for notifying Gilead Sciences, and the IRB if unexpected and/or serious events occur. An 
independent physician safety monitor who is not otherwise involved in the study will be identified and review the 
safety data once per month or more frequently as needed throughout the period of study implementation, discuss 
study medication management, and address any potential safety concerns. 
 
Clinical Data and Safety Review 
The PI is responsible for the initial evaluation and reporting of safety information at the participant level and for 
alerting Gilead Sciences if unexpected concerns arise. Additional reviews may be conducted as dictated by the 
occurrence of certain events. 
The PI and research team will review incoming safety data on an ongoing basis. Events identified as 
questionable, inconsistent, or unexplained will be queried for verification. The PI and the independent safety 
monitor will meet approximately every month to review clinical data reports. The content, format and frequency 
of the clinical data reports will be agreed upon by the independent safety monitor, Gilead Science and the 
research team in advance of study implementation. In addition to routine safety data reviews, the independent 
safety monitor and study investigators will convene on an ad hoc basis to make decisions regarding the handling 
of any significant safety concerns. If necessary, external experts representing expertise in the fields of 
pregnancy, infectious diseases, hepatology and medical ethics may be invited to join the safety review. A 
recommendation to pause or stop the trial may be made at this time or at any such time that the safety review 
team agrees that an unacceptable type and/or frequency of AEs has been observed. 
Adverse Events Definitions and Reporting Requirements 
Adverse Events  
An AE is defined as any untoward medical occurrence in a clinical research participant administered an 
investigational medication and which does not necessarily have a causal relationship with the investigational 
medication. As such, an AE can be an unfavorable or unintended sign (including an abnormal laboratory finding, 
for example), symptom or disease temporally associated with the use of an investigational medication, whether 
or not considered related to the medication. The term “investigational medication” for this study refers to the 
study medication. 
Study participants will be provided instructions for contacting the study site to report any untoward medical 
occurrences they may experience throughout their participation in the study. Since the women enrolled in this 
study will be receiving prenatal care at Magee-Womens Hospital the women will be instructed to come to Magee-
Womens Hospital if they experience any adverse events requiring evaluation. Participants will be seen by a 
physician investigator/study clinician. In cases of potentially life-threatening events, participants will be instructed 
to seek immediate emergency care. With appropriate permission of the participant, whenever possible, records 
from all non-study medical providers related to untoward medical occurrences will be obtained and required data 
elements will be abstracted and recorded on study CRFs. All participants reporting an untoward medical 
occurrence will be followed clinically until the occurrence resolves (returns to baseline) or stabilizes. 
Study site staff will document all AEs reported by or observed in enrolled study participants regardless of severity 
and presumed relationship to investigational medication, including gradable laboratory findings. AE severity will 
be graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 1.0, December 2004 
(Clarification dated August 2009). 


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Serious Adverse Events  
An SAE will be defined as an AE that:  
 
Results in death 
 
Is life-threatening  
 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 
Results in persistent or significant disability/incapacity  
 
Is a congenital anomaly/birth defect 
 
Is an important medical event that may not result in death, be immediately life-threatening, or require 
hospitalization but may jeopardize the participant or require intervention to prevent one of the outcomes 
listed in the definition above. 
 
Adverse Event Relationship to Study Medication 
Relatedness is an assessment made by the physician investigator of whether or not the event is related to the 
study agent.  
 
Related: There is a reasonable possibility that the AE may be related to the study agent(s) 
 
Not Related: There is not a reasonable possibility that the AE is related to the study agent(s) 
Expedited Adverse Event Reporting Requirements  
Reporting Requirements for this Study 
All adverse events will be reported to Gilead Sciences on a monthly basis.  All serious adverse events will be 
reported to the University of Pittsburgh Institutional Review Board, the FDA and Gilead Sciences according to 
the University of Pittsburgh IRB’s reporting guidelines.   
Grading Severity of Events 
The most current Division of DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS 
AE Grading Table) is available on the RSC website at http://rsc.tech-res.com/safetyandpharmacovigilance/. 
Regulatory Requirements 
Information on all reported AEs will be included in reports to the FDA and other applicable government and 
regulatory authorities. The Protocol Chair will submit AE information in accordance with the requirements of the 
University of Pittsburgh IRB. 
Social Harms Reporting 
Although every effort will be made to protect participant privacy and confidentiality, it is possible that participants’ 
involvement in the study could become known to others and that social harms may result. Social harms that are 
judged by the study investigators to be serious or unexpected will be reported to Gilead Sciences and to the 
University of Pittsburgh IRB.   
Managing any potential emotional distress from participating in this study: 
From prior studies, we have established relationships with experts in the fields of mental health, social work, 
and intimate partner violence, and with their advice we have developed several strategies to minimize and 
manage potential emotional distress that may occur as a result of participating in our research study.  
The research staff and investigators who will be conducting the research activities will be trained regarding 
how to handle any situations in which a patient reveals her desire to change her situation, asks for additional 


SOF/VEL in postpartum women with OUD, Version 8.0 
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26 
 
advice or information regarding her alcohol or drug use, reveals other risks such as depression or suicidality, or 
discloses that she may be in grave danger.  
Because problems with alcohol, drug, and persistent tobacco use in women are often associated with other 
issues such as mental illness and intimate partner violence (IPV), all research team members will receive 
training in identifying and dealing with crises associated with these other conditions.  
In any of the above cases or in the case that participation in the study elicits any emotional distress, Magee-
Womens Hospital social workers will be available at all times by pager. All of these social workers have 
received extensive training in behavioral health assessment/management, suicide intervention, and IPV and 
crisis management. Clinical investigators will also be available for consultation on difficult cases at all times by 
pager. The Women’s Center and Shelter of Greater Pittsburgh’s telephone hotline, supported 24 hours a day, 
will also be available. Although we recognize that contacting the social workers for intervention with our study 
participants constitutes an intervention that directly impacts the study results, our first priority is the safety and 
well-being of our participants. In these situations, we will first ensure the appropriate care of the participants 
and then account for the events when performing our analyses.  
Any participants who are in immediate danger, threaten suicide, or constitute any potential harm to others will 
be immediately referred to social workers or behavioral medicine experts who are on call for all hospital 
patients. The usual protocol for social work or behavioral medicine in our institution is to communicate and 
collaborate with the obstetric care providers. We will thus leave the decision to contact and inform the obstetric 
care providers of any relevant and ongoing behavioral health concerns to the social work or behavioral 
medicine experts. 
CLINICAL MANAGEMENT 
Guidelines for clinical management and permanent discontinuation of study medication are outlined in this 
section. In general, the physician investigators will only discontinue study medication if they feel that the risk of 
study medication continuation outweighs the benefits of study medication continuation. The physician 
investigators will document all permanent discontinuations on applicable CRFs. 
 
Grading System 
AE severity grading is described in Section 8.3.1. 
Dose Modification Instructions 
No dose modifications will be permitted in this study. 
General Criteria for Permanent Discontinuation of Study Medication 
A participant will be permanently discontinued from medication use by the physician investigators for any of the 
following reasons, according the HCV treatment guidelines:  
 
5-fold or greater increase in ALT or AST at the V1 or V2 compared to baseline result (screening visit), 
confirmed by immediate repeat testing 
 
Any increase of ALT or AST of less than 5-fold from baseline (screening visit) V1 or V2 visit that is 
accompanied by any weakness, nausea, vomiting, or jaundice 


SOF/VEL in postpartum women with OUD, Version 8.0 
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27 
 
 
3-fold or greater increase in ALT or AST accompanied by bilirubin >2x the upper limit of normal, confirmed 
on immediate repeat testing 
 
HIV seroconversion occurs during the time of study medication use 
 
Participant is unable or unwilling to comply with required study procedures 
 
If the participant desires to breastfeed  
 
Participant might be put at undue risk to their safety and well-being by continuing medication use, 
according to the judgment of the study investigators. The study investigators will consult with the 
independent safety physician prior to all study medication discontinuation instituted for this reason.  
Any time a participant is permanently discontinued from study medication (prior to completion of the 12 week 
course of study medication), HCV resistance testing will be performed.  
Permanent Discontinuation in Response to Adverse Events 
Grade 1 or 2 
In general, a participant who develops a Grade 1 or 2 AE as defined by the DAIDS Table for Grading Adult and 
Pediatric Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009) regardless of 
relationship to study medication will continue study medication use.  
Grade 3 
For participants who develop a Grade 3 AE as defined by the DAIDS Table for Grading Adult and Pediatric 
Adverse Events, Version 1.0, December 2004 (Clarification dated August 2009) that is judged by the study 
investigators to be unrelated to study medication, the study medication will continue.  The study medication must 
be permanently discontinued for participants who develop a Grade 3 AE judged by a physician investigators to 
be related to the study medication. 
Grade 4 
If a participant develops a Grade 4 AE as defined by the DAIDS Table for Grading Adult and Pediatric Adverse 
Events, Version 1.0, December 2004 (Clarification dated August 2009) and the AE is determined to be related 
to study medication, then study medication must be permanently discontinued. 
Any time a participant is permanently discontinued from study medication (prior to completion of the 12 week 
course of study medication), HCV resistance testing will be performed. 
HIV-1 Infection 
Participants who are positive for HIV (known or positive at Screening) will not be eligible to participate.  If HIV 
seroconversion occurs during the time of study medication use, the participant will be permanently discontinued 
from medication use by the physician investigators.     
Criteria for Early Termination of Study Participation  
Participants may voluntarily withdraw from the study for any reason at any time. The study investigators also 
may withdraw participants from the study to protect their safety and/or if they are unwilling or unable to comply 
with required study procedures. Participants also may be withdrawn if Gilead Sciences, government or regulatory 
authorities, including the FDA and Office for Human Research Protections (OHRP), or site IRBs/ECs terminate 
the study prior to its planned end date. Detailed reason with the withdrawal of a participant will be documented 
in the research record.  Every reasonable effort will be made to continue to follow the participant as scheduled 
for safety      
STATISTICAL CONSIDERATIONS 


SOF/VEL in postpartum women with OUD, Version 8.0 
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Overview and Summary of Design 
This is a Phase IV, single-arm, open label pilot study of immediate postpartum treatment for chronic HCV 
infection in 30 HCV-infected women with Opioid Use Disorder with a 12-week course of SOF/VEL FDC. 
Study Endpoints 
Pregnant women meeting all of the criteria in section 5.2 and 5.3 will be enrolled into the study and followed 
prospectively through delivery and 18 months postpartum. Study medication will be initiated in the immediate 
postpartum period (1-14 days after delivery).  Infants will be enrolled upon delivery and their medical records 
will be reviewed at approximately 18 months of age. 
Primary Endpoints 
 
Treatment feasibility will be established through the successful recruitment and enrollment of 
participants, administration of sofosbuvir/velpatasvir in the postpartum period and ability to determine 
SVR at 3 months following treatment completion.  
 
Acceptability of sofosbuvir/velpatasvir will be evaluated by self-report of treatment side effects and 
barriers and facilitators to treatment adherence.  
 
Adherence to sofosbuvir/velpatasvir will be evaluated with medication diaries, an assessment of missed 
doses, pill counts and attendance at opioid maintenance treatment visits. 
Secondary Endpoints 
 
Breast milk concentrations of SOF, GS-331007, and VEL 
 
Rates of IVDU recidivism 
 
HCV reinfection 
 
Patient centered outcomes such as health related QOL will be assessed at 6, 9 and 12 months 
following treatment completion 
Sample Size 
To evaluate the primary objective, we estimate a desired sample size of 30 participants. A subset of 5 
participants will participate in the PK visits. Approximately 375 OD pregnant patients receive prenatal and 
postpartum care at MWH each year and approximately 50% are HCV infected. Anticipating a 75% enrollment 
rate, 30 HCV infected pregnant patients will be available for participation following a 12 month enrollment 
period. 
Participant Accrual and Retention 
Pregnant and postpartum chronically HCV-infected women who meet the criteria outlined in Section 5 and are 
interested in participating, will be enrolled into this study. Once a participant is enrolled, the study staff will 
make every reasonable effort to retain her for the entire study period to minimize possible bias associated with 
loss-to-follow-up. Participant contact information will be reviewed at each follow-up visit and participants will be 
asked to contact study staff if their contact information changes. If a participant cannot be contacted using her 
primary contact information, alternative contacts will be called in order to reach the participant.  A maximum of 
10% loss-to-follow-up will be targeted. 
Data Analysis 
Validated survey instruments will be used to collect data on patient-centered outcomes such as HCV health 
related quality of life (QOL). Protocol-specific survey instruments will be used to record treatment side effects, 
medication diaries, an assessment of missed doses and pill counts. All responses to data collection materials 
will be transferred into a secure database. Preliminary statistical analyses will focus on data checks for 


SOF/VEL in postpartum women with OUD, Version 8.0 
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29 
 
completeness and accuracy and address any issues with data quality. Descriptive summaries will include the 
mean and standard deviations (or medians and quartiles for skewed distributions) for continuous variables and 
frequencies and proportions for categorical variables. 95% confidence intervals for means and proportions will 
be calculated. To visually examine distributions, boxplots and histograms will be constructed for continuous 
variables. Poisson regression analyses will be conducted for rates of SVR following treatment. Logistic 
regression analysis will be used for the remaining dichotomous outcome variables (IVDU relapse, HCV 
reinfection). Outcomes will be summarized overall and by race, age, parity, income, and insurance. All 
analyses will be conducted using STATA (StataCorp. 2013. Stata Statistical Software: Release 13. College 
Station, TX). 
Analysis of SVR12 
Approximately 98% of patients treated with SOF/VEL for 12 weeks obtained an SVR12.  Therefore, we 
estimate that at least 29 out of the 30 chronically HCV-infected postpartum women will have a SVR12 after 
treatment.   
Analysis of breastmilk pharmacokinetics 
Drug concentrations in breastmilk and plasma will be listed and summary statistics will be used to describe the 
derived PK parameters. Nonlinear mixed effects modeling will be used to determine the pharmacokinetics of 
SOF, GS-331007, and VEL in breastmilk and plasma. The ratio of milk to plasma will be reported.   
Analysis of Safety Endpoints 
Rates of abnormal safety laboratory assessments will be compared to those reported in the literature on 
historic controls. Statistical significance will be determined by chi-square test. 
Study Oversight 
No Data and Safety Monitoring Board oversight is planned for this study, however, a medical monitor will 
provide oversight for this study. The medical monitor will be an independent physician investigator from the 
University of Pittsburgh who has experience monitoring clinical trials among subjects with chronic HCV 
infection. Reviews of study progress, including rates of participant accrual, retention, completion of primary and 
main secondary endpoint assessments will take place approximately every 3 months, and as needed.  At the 
time of these reviews, or at any other time, the medical monitor may recommend that the study proceed as 
designed, proceed with design modifications, or be discontinued.   
 
DATA HANDLING AND RECORDKEEPING 
Data Management Responsibilities 
Study Case Report Forms will be developed by the study team in conjunction with data management.  
Source Documents and Access to Source Data/Documents 
The site will maintain source data/documents in accordance with current DAIDS policies. (http://rsc.tech-
res.com/policiesandregulations/)  
The study team will maintain, and store securely, complete, accurate and current study records throughout the 
study. In accordance with U.S. regulations regarding testing investigational medications, the study investigator 
will maintain all study documentation for at least two years following the date of marketing approval for the study 
medications being tested for the indication in which they were studied. If no marketing application is filed, or if 
the application is not approved, the records will be retained for two years after the investigation is discontinued 


SOF/VEL in postpartum women with OUD, Version 8.0 
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30 
 
and the US FDA is notified. For research involving children, records shall be retained at least until the pediatric 
subject reaches the age of 23. 
Study records will be maintained on site for the entire period of study implementation. All physical source 
documents will be stored in the participant’s study chart, labeled with the participant ID number in a locked file 
cabinet in a locked office in the Pregnancy Recovery Center. All interactions with patients should be tracked, 
including but not limited to: dates they were called enrolled, recruited and consented, dates they completed each 
survey, dates interviewed, interviewer, dates they were contacted (and method of contact) to completed all follow 
up assessments, dates they completed follow up assessments, any and all study payments using the Participant 
Tracking Database. This database is password-protected and will be backed up weekly 
Quality Control and Quality Assurance 
The study site will conduct quality control and quality assurance procedures in accordance with site SOPs.  
CLINICAL SITE MONITORING 
As this is an investigator initiated study, monitoring will be performed by the clinical study staff (i.e. QA/QC 
Reviewer), PoR, laboratory staff and local data management team.   Internal reviews will include: 
 
Review informed consent forms, protocol procedures, and study documentation 
 
Assess compliance with the study protocol, Good Clinical Practices (GCP) guidelines, and applicable 
regulatory requirements (US and non-US), including CFR Title 45 Part 46 and Title 21 Parts 50, 56, and 
312  
 
Perform source document verification to ensure the accuracy and completeness of study data 
 
Verify proper collection and storage of biological specimens 
 
Verify proper storage, dispensing, and accountability of investigational study medications 
 
The Education and Compliance Office for Human Subject Research (ECO-HSR), Research Conduct and 
Compliance Office will also oversee study activities.  The ECO-HSR has extensive experience in the auditing 
and monitoring of clinical investigations for compliance with GCP standards and IND commitments. To ensure 
appropriate institutional oversight of University-based IND applications, the ECO-HSR will periodically monitor 
the research oversight programs of IND Sponsors, which will include compliance of the Sponsor and 
Investigator with applicable FDA regulations, applicable University of Pittsburgh policies and the IRB-approved 
protocol and consent document. The frequency of these monitoring visits shall be determined by the ECO-HSR 
The study investigators also will allow inspection of all study-related documentation by authorized 
representatives of Gilead Sciences, FDA, OHRP, IRBs/ECs and other local and US regulatory authorities.  
HUMAN SUBJECTS PROTECTIONS 
Study investigators will make efforts to minimize risks to participants. Informed consent will be reviewed in 
detail with potential participants and all questions will be adequately answered prior to obtaining written 
informed consent.  All eligibility criteria will be verified prior to initiation of investigational product.  Recruitment 
will begin after receiving IRB approval and after the protocol has been submitted to the FDA.  The study 
investigators will permit audits by the NIH, Gilead Sciences, the FDA, OHRP, IRB, and other local and US 
regulatory authorities or any of their appointed agents. 
Institutional Review Boards 
The study staff will ensure that the protocol, associated informed consent form, and study-related documents 
(such as participant education and recruitment materials) are reviewed and approved by the University of 


SOF/VEL in postpartum women with OUD, Version 8.0 
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31 
 
Pittsburgh IRB prior to starting the study. Any amendments to the protocol or informed consent will be approved 
by the University of Pittsburgh IRB prior to implementation. 
Study Coordination 
Elizabeth Krans MD MSc is the study principal investigator. Assignment of all sponsor responsibilities for this 
study will be specified in a Clinical Trials Agreement (CTA) executed by the University of Pittsburgh and Gilead 
Sciences. 
Close coordination between the study team is necessary to track recruitment, enrollment, retention, AEs and 
unanticipated problems and to address other issues that may arise in a timely manner. The study investigators 
and the independent safety physician will address issues related to study eligibility, AE management/reporting 
and unanticipated problems as needed to assure consistency. Rates of accrual, protocol adherence, retention, 
and AE incidence will be reported by data management and monitored closely by the team as well as the Study 
Steering Committee. 
Risk Benefit Statement 
Risks 
As with any research study, there may be adverse events or side effects for the maternal participant that are 
currently unknown and certain of these unknown risks could be permanent, severe or life-threatening. 
It is also not known if SOF/VEL is present in human breast milk.  If the participant intends to breast feed, she will 
not be eligible to enroll in this study.  
There is a potential risk that the hepatitis virus may become resistant to SOF/VEL if the participant does not 
complete the entire 12 weeks of study medication.  If resistance occurs, this may limit the choices of effective 
therapy after pregnancy for the participant.  
The following side effects have been associated with the use of oral SOF/VEL used daily for 12 weeks of duration 
in men and non-pregnant women. With the exception of asthenia, each of these adverse reactions occurred at 
a similar frequency or more frequently in subjects treated with placebo compared to subjects treated with 
SOF/VEL (asthenia: 3% versus 5% for the placebo and SOF/VEL groups, respectively). 
 
Percentage of Participants 
N=624 
Headache 
22% 
Fatigue 
15% 
Nausea 
9% 
Asthenia 
5% 
Insomnia 
5% 
 
There are risks of alterations in laboratory values with the use of this medication.  Previous studies have shown 
the following: 
Lipase Elevations: In ASTRAL-1, isolated, asymptomatic lipase elevations of greater than 3xULN were 
observed in 3% and 1% of subjects treated with SOF/VEL and placebo for 12 weeks, respectively; and in 6% 
and 3% of subjects treated with SOF/VEL in ASTRAL-2 and ASTRAL-3, respectively.  
Creatine Kinase: In ASTRAL-1, isolated, asymptomatic creatine kinase elevations greater than or equal to 
10xULN were reported in 1% and 0% of subjects treated with SOF/VEL and placebo for 12 weeks, 
respectively; and in 2% and 1% of subjects treated with SOF/VEL in ASTRAL-2 and ASTRAL-3, respectively.  


SOF/VEL in postpartum women with OUD, Version 8.0 
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32 
 
There are known drug interactions with SOF/VEL and other prescription and non-prescription medications.  A 
comprehensive list of medications will be obtained from participants including over-the-counter medications (i.e. 
antacids, St. John’s wort) and compared to the package insert to assess any contraindication to participation or 
necessary alterations in dosing schedules with use of the study medication.   
Phlebotomy or starting an IV may lead to excessive bleeding, discomfort, feelings of dizziness or faintness, 
and/or bruising, swelling and/or infection.  
Disclosure of HIV status may cause worry, sadness or depression. Disclosure of HIV-positive status has been 
associated with depression, suicidal ideation, and denial as well as social isolation. Trained counselors will be 
available to help participants deal with these feelings.  
Participation in clinical research includes the risks of confidentiality loss. 
Participants will be asked to provide personal/protected health information (PHI).  All attempts will be made to 
keep PHI confidential within the limits of the law.  However, there is a chance that unauthorized persons will see 
PHI.  All paper records will be kept in a locked file cabinet or maintained in a locked room at Magee.  Electronic 
files will be password protected.  Only people who are involved in the conduct, oversight, monitoring, or auditing 
of this study will be allowed access to the PHI that is collected.  Any publications from this study will not use 
information that will identify participants by name.  Organizations that may inspect and/or copy research records 
maintained at the participating sites for quality assurance and data analysis include groups such as the study 
sponsor, the National Institute of Health (NIH) or its designee and the US Food and Drug Administration (FDA). 
Benefits 
Participants may or may not benefit from being in this study. Participants may benefit from this study though the 
opportunity to receive treatment for their chronic HCV.  Participants and others may benefit in the future from 
information learned from this study. Specifically, information learned in this study may lead to evidence-based 
guidance for the treatment of chronic hepatitis C infection in the postpartum period in conjunction with opioid 
maintenance treatment.  
Informed Consent Process 
Written informed consent will be obtained from each study participant prior to performing study procedures. In 
obtaining and documenting informed consent, the study investigators will comply with applicable local and US 
regulatory requirements and will adhere to GCP and to the ethical principles that have their origin in the 
Declaration of Helsinki. Participants will be provided with a copy of the informed consent form if they chose. 
The informed consent process will cover all elements of informed consent required by research regulations. In 
addition, the process specifically will address the following topics of importance to this study: 
 
The safety and efficacy profile of the study medication 
 
The importance of daily adherence to the study medication 
 
The importance of adherence to the study visit and procedures schedule  
 
The potential medical risks of study participation (and what to do if such risks are experienced) 
 
The potential social harms associated with study participation (and what to do if such harms are 
experienced) 
 
The benefits of study participation  
 
The distinction between research and clinical care 
 
The right to withdraw from the study at any time 


SOF/VEL in postpartum women with OUD, Version 8.0 
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33 
 
 
Optional participation in the breastmilk PK portion of the study. Participants who wish to participate in 
the PK portion of the study will sign an additional informed consent form covering the procedures and 
potential risks and benefits of participating in this portion of the study.  
Participant Confidentiality 
All study procedures will be conducted in private, and every effort will be made to protect participant privacy and 
confidentiality to the extent possible. All study-related information will be stored securely at Magee Medical 
Building. All participant information will be stored in locked areas with access limited to the clinical study staff. 
All laboratory specimens, study data collection, and administrative forms will be identified by coded number 
(PTID) only to maintain participant confidentiality. All records that contain names or other personal identifiers, 
such as locator forms and informed consent forms, will be stored separately from study records identified by 
code number following completion of the study. All local databases will be secured with password protected 
access systems. Forms, lists, logbooks, appointment books, and any other listings that link participants’ ID 
numbers (PTID) to identifying information will be stored in a separate, locked area with limited access. 
Participants’ study information will not be released without their written permission, except as necessary for 
review, monitoring, and/or auditing by the following: 
 
Representatives of the US Federal Government, including the US FDA, the US OHRP and other local 
and US regulatory authorities 
 
Representatives of Gilead Sciences 
 
Study staff  
 
University of Pittsburgh IRB 
Special Populations 
Pregnant Women 
Pregnant women will be offered enrollment in this study in accordance with guidelines set forth in the US 45 CFR 
46. 
Children 
Infant procedures will be conducted in accordance with guidelines set forth in the US 45 CFR 46 and DAIDS 
policy 
(http://www.niaid.nih.gov/LabsAndResources/resources/DAIDSClinRsrch/Documents/enrollingchildrenrequirem
ents.pdf).  
Compensation 
Pending IRB approval, participants will be compensated for time and effort in this study, and/or be reimbursed 
for travel to study visits and time away from work. Reimbursement amounts will be specified in the informed 
consent form.  Compensation may include parking/bus passes and additional incentives for making study 
appointments within the window period. 
Communicable Disease Reporting 
Study staff will comply with local requirements to report communicable diseases including HIV-1 identified among 
study participants to health authorities. Participants will be made aware of reporting requirements during the 
informed consent process. 
Access to HIV-related Care 
HIV Counseling and Testing 


SOF/VEL in postpartum women with OUD, Version 8.0 
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34 
 
HIV testing will be performed at Screening. HIV test-related counseling will be provided to all potential study 
participants who consent to undergo HIV-1 screening to determine eligibility for participation.  Counseling will be 
provided in accordance with standard HIV counseling policies and methods.  Participants will also have HIV 
screening as part of routine prenatal care at 28 weeks’ gestation, and if clinically indicated during the study. 
Care for Participants Identified as HIV-Positive 
Identified as HIV-Positive Prior to Enrollment 
An individual who has been identified as infected with HIV-1 will not be eligible to participate and will be referred 
to the Pittsburgh AIDS Center for Treatment (PACT).  
Identified as HIV-Positive While on Study Medication 
The participant will discontinue with the study medication and study procedures, and will be immediately referred 
to PACT.   
Study Discontinuation 
This study may be discontinued at any time by Gilead Sciences, the US FDA, the OHRP, other government or 
regulatory authorities, or the University of Pittsburgh IRB. 
PUBLICATION POLICY 
The University of Pittsburgh study investigators will be responsible for publication of the results of this study. 
The manuscript draft will be sent to Gilead Sciences 30 days prior to submission for their review and approval.   
APPENDIX 
APPENDIX I: SCHEDULE OF STUDY VISITS AND EVALUATIONS  


SOF/VEL in postpartum women with OUD, Version 8.0 
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35 
 
  
  
Screening A 
(V1) 
Screening B 
(V2) 
Enrollment 
(V3) 
Treatment 
Initiation (V4)
Breastmilk 
PK Visits* 
Treatment 
Follow Up 
(V5-9) 
End of 
Treatment 
(V10) 
Post 
treatment 
(V11) 
12 month 
follow up 
(V12) 
End of Study 
(V13) 
ADMINISTRATIVE AND REGULATORY 
Informed consent(s) 
X 
 
X  
 
X 
  
 
  
  
 
Assess informed consent comprehension 
 
 X 
 
 
  
 
  
  
 
Sign medical record releases 
X 
 
 
X 
 
 
 
 
X 
X 
Assignment of PTID 
 
 X 
 
 
  
 
  
  
 
Collect/review locator information 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Visit questionnaire 
 
X 
 
 
 
X 
X 
X 
 
X 
Eligibility assessment  
X 
X 
  
 
 
  
 
  
  
 
Eligibility confirmation 
  
X 
X 
X 
 
  
 
  
  
 
Reimbursement 
 
 
 
 
X 
 
 
 
 
 
Record/ update AEs 
  
 
  
 
X 
X 
X 
X 
X 
X 
Schedule next visit  
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
BEHAVIORAL 
Protocol adherence counseling 
  
X 
X 
X 
X 
X 
X 
X 
X 
 
Contraception counseling 
 
 
 
X 
 
 
 
 
 
 
Medication use/adherence counseling 
  
 
X 
X 
X 
X 
 *** 
  
 
Qualitative interview 
 
 
 
 
 
 
X 
 
 
X 
CLINICAL 
  
 
  
 
 
  
 
  
  
 
Review medical history and medical 
records, document findings 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
 
X 
X 
 
Consult with hepatologist 
 
X 
X 
 
 
 
*** 
X 
 
 
Physical examination (full or modified) 
X 
X 
 
 
 
 
Provide available test results 
 
X 
X 
 
X 
X 
X 
X 
X 
Administer timed medication dose 
 
 
 
 
X 
 
 
 
 
 
LABORATORY  
  
 
  
 
 
  
 
  
  
 
 
Collect breastmilk 
 
 
 
 
X 
 
 
 
 
 
BloodHIV 
Collect Blood 
X 
  
X 
X 
 X 
X 
X  
X  
 
HCV antibody 
X** 
 
 
 
 
 
 
 
 
 
HCV RNA viral load 
X** 
 
 
 
X (V6 or 7)
X 
X 
X 
 
HCV Genotype 
X** 
 
 
 
 
HCV Resistance testing 
 
 
 
 
 
 
*** 
*** 
 
 
HepBsAg 
X** 
 
  
 
 
  
 
  
  
 
HepBcAb, HepBsAb 
 
X 
 
 
 
 
 
 
 
 
HepA total Ab 
 
X 
 
 
 
 
 
 
 
 
HIV 
X* 
 
 
 
 
 
 
 
 
 
CBC 
 
 
 
X* 
 
X (V6 or 7, 
V8
9)
X 
X 
X 
 
 
CMP 
 
X 
 
X* 
 
X (V6 or 7, 
X 
X 
X 
 
 
GGT 
 
 
 
X 
 
X (V6 or 7, 
X 
X 
X 
 
 
PK sampling breastmilk and blood 
 
 
 
 
X 
 
 
 
 
 
STUDY MEDICATION 
 
 
  
 
 
  
 
  
  
 
Provision of Study Medication  
  
 
X 
X 
X 
 
  
  
 
Collect Remaining Study Medication 
  
 
  
 
 
X 
  
 
*For a subset of participants, n=5 **If not collected as part of standard prenatal/postpartum care; can be collected at V2 if within 3 months of treatment initiation ***If 
clinically indicated