Rapid HCV Test and Treat to Increase HCV Treatment Uptake Among People Who Use Drugs
Phase: NA
Conditions: Hepatitis C Virus Infection, Response to Therapy of
Sponsor: Johns Hopkins University

 
ClinicalTrials.gov  
Submitted Document  
COVER PAGE 
 
 
Official Title of Study: 
Rapid HCV Test and Treat to increase HCV treatment among 
people who use drugs (RAPID-HCV) 
NCT Number: 
NCT04677153 
Document Type: 
Study Protocol that also includes a Statistical Analysis Plan (SAP) 
Document Version: 
5.2 
Date document was 
last updated: 
Feb 9, 2024 
Key Update: 
Increased number of qualitative interviews for qualitative analysis to 
meet thematic saturation. 
IRB Approval Date (For 
updated document): 
March 12, 2024 
 
 
 
 

 
 
 
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Protocol for Study B20-237 
Rapid HCV Treatment Access for Persons Who Use Drugs (RAPID-HCV) 
 
VERSION: 
5.2 
 
 
SPONSOR: 
Johns Hopkins 
University  
NUMBER OF SITES: 
5 
ABBVIE 
INVESTIGATIONAL 
PRODUCT: 
Glecaprevir, 
Pibrentasvir 
IND EXEMPT   
 
 
FULL TITLE:  Rapid HCV Test and Treat to increase HCV treatment uptake among people who use drugs 
(RAPID-HCV) 
 
 
PRINCIPAL INVESTIGATOR(S):  
Oluwaseun Falade-Nwulia, MD 
EMERGENCY MEDICAL CONTACT: 
 
Oluwaseun Falade-Nwulia, MD 
5200 Eastern Avenue 
Mason F. Lord Center Tower, Suite 381 
Baltimore, MD 21224 
Email: ofalade1@jhmi.edu 
Phone: 410-955-7538 
 
 
 

 
 
 
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TABLE OF CONTENTS 
1 
SYNOPSIS 
5 
2 
INTRODUCTION 
6 
2.1 
BACKGROUND AND RATIONALE 
6 
2.2 
CLINICAL HYPOTHESIS 
7 
3 
STUDY OBJECTIVES AND ENDPOINTS 
7 
3.1 
OBJECTIVES 
7 
3.2 
PRIMARY ENDPOINT 
7 
3.3 
SECONDARY ENDPOINTS 
8 
3.4 
EXPLORATORY ENDPOINTS 
8 
4 
INVESTIGATIONAL PLAN 
8 
4.1 
OVERALL STUDY DESIGN AND PLAN 
8 
4.2 
STUDY PROCEDURES 
10 
5 
STUDY ACTIVITIES 
15 
5.1 
INCLUSION AND EXCLUSION CRITERIA 
15 
5.2 
CONTRACEPTION RECOMMENDATIONS 
16 
5.3 
PROHIBITED MEDICATIONS AND THERAPY 
17 
5.4 
PRIOR AND CONCOMITANT THERAPY 
17 
5.5 
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY 
18 
5.6 
FOLLOW-UP FOR SUBJECT WITHDRAWAL FROM STUDY 
18 
5.7 
STUDY DRUG 
19 
5.8 
PROTOCOL DEVIATIONS 
20 
5.9 
STUDY LABS 
20 
6 
SAFETY CONSIDERATIONS 
21 
6.1 
KNOWN AND POTENTIAL RISKS TO PARTICIPANTS 
21 
6.2 
COMPLAINTS AND ADVERSE EVENTS 
21 
6.3 
TOXICITY MANAGEMENT 
23 
6.4 
PRODUCT COMPLAINT 
24 

 
 
 
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7 
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE 
24 
7.1 
STATISTICAL AND ANALYTICAL PLANS 
24 
7.2 
DEFINITION FOR ANALYSIS POPULATIONS 
24 
7.3 
STATISTICAL ANALYSES 
25 
8 
ETHICS 
27 
8.1 
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB) 
27 
8.2 
ETHICAL CONDUCT OF THE STUDY 
27 
8.3 
SUBJECT CONFIDENTIALITY 
27 
8.4 
JOHNS HOPKINS UNIVERSITY TRANSPLANT ONCOLOGY AND INFECTIOUS DISEASES CLINICAL RESEARCH CENTER (TOID CRC) 27 
9 
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION 
28 
10 DATA QUALITY ASSURANCE 
28 
11 COMPLETION OF THE STUDY 
28 
12 REFERENCES 
29 
LIST OF TABLES 
TABLE 1: SUMMARY OF IMPLEMENTATION OUTCOMES USING THE RE-AIM FRAMEWORK ................................ 14 
TABLE 2: IDENTITY OF STUDY DRUG .................................................................................................................. 19 
LIST OF FIGURES 
FIGURE 1: HCV TREATMENT BARRIERS................................................................................................................ 7 
FIGURE 2: STUDY SCHEMA ................................................................................................................................. 9 
LIST OF APPENDICES 
APPENDIX A. SCHEDULE OF EVENTS (ALL PARTICIPANTS) 
31 
APPENDIX B. SCHEDULE OF EVENTS (PARTICIPANTS WHO DO NOT START HCV TREATMENT IN EITHER ARM) 
32 
APPENDIX C. STUDY SPECIFIC ABBREVIATIONS AND TERMS 
33 

 
 
 
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APPENDIX D. RESPONSIBILITIES OF THE INVESTIGATOR 
35 
APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
36 
 

 
 
 
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1 SYNOPSIS 
TITLE: Rapid HCV Test and Treat to increase HCV treatment among people who use drugs (RAPID-
HCV)   
DESIGN: Open label multicenter, phase IV randomized trial of a test and treat strategy with peer 
enhancement for HCV treatment at drug treatment programs versus standard of care referral for 
HCV treatment. 
DURATION: Participants will be on study for up to a total of 12 months after HCV treatment 
initiation (treatment and observation period).  
SAMPLE SIZE: 124 HCV infected participants will be enrolled in the study from five drug treatment 
programs in four cities (Baltimore Maryland, Birmingham Alabama, San Francisco California and 
Toronto Canada). Up to 15 peers and 45 drug treatment program staff members (for in-depth 
interviews only) will be enrolled across all sites. Total enrollment up to 184 participants.  
POPULATION: People who use drugs enrolled in drug treatment programs with confirmed ongoing 
HCV infection. 
All participants ≥ 18 years of age enrolled at study drug treatment sites who have ongoing HCV 
infection (as determined through study testing procedures).  
STUDY DRUG AND DURATION OF TREATMENT: Subjects will receive GLE/PIB fixed-dose 
combination (300 mg/120 mg) QD for 8 weeks. 
 
 

 
 
 
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2 INTRODUCTION 
2.1 
Background and Rationale 
Why Is This Study Being Conducted? 
Hepatitis C virus (HCV) infection is a major public health challenge and is associated with significant 
morbidity and mortality.1 The World Health Organization (WHO) has called for elimination of HCV as a 
public health challenge by the year 2030. The WHO elimination goals include a 90% reduction in HCV 
incidence and a 65% reduction in HCV related mortality by 2030 relative to 2015 rates.2 However, the 
United States is experiencing increases in HCV incidence directly attributable to injection drug use with 
the steepest increase in incidence since 2011.3,4 Although people who use drugs (PWUD) have 
disproportionately high rates of HCV infection, rates of HCV treatment remain low among PWUD.5,6 
Once initiated on HCV therapies, PWUD have been demonstrated to achieve high rates of HCV cure.7  
 
HCV treatment uptake among PWUD, the core of the HCV epidemic, remains low due to multiple 
interrelated barriers at the level of the patient, the provider, and the system.8-10 Patient-level barriers 
include poor knowledge related to HCV and its treatment and absence of symptoms. These issues are 
compounded by general barriers to health care access (e.g., not having insurance or a primary care 
provider), competing comorbidities, which may require more immediate attention, and factors that 
impede stability, such as ongoing Substance Use Disorder (SUD), unemployment, and  lack of 
transportation.11-13 In many parts of the world, the major structural barrier of medication cost has been 
reduced through insurance coverage for HCV treatment by payers and removal of insurance coverage 
restrictions related to drug use or liver disease stage. Beyond cost, additional structural barriers include 
insufficient HCV treatment locations. HCV care has historically been delivered in specialist settings thus 
segregating HCV treatment from other services that PWUD utilize including those received at opioid 
treatment programs (OTPs).  
 
Drug treatment programs such as OTPs routinely provide services for PWUD, with many patients 
accessing care at these settings multiple times a week. The structure of care provision at OTPs including 
observed dosing of opioid agonist therapies, offers a unique infrastructure upon which to layer HCV 
treatment. In addition, simplification of HCV treatment protocols endorsed by the major guidelines 
including the AASLD/IDSA14 provide an opportunity to implement HCV treatment in non-traditional 
settings. We propose to evaluate effectiveness of an HCV test and treat strategy at OTPs, a venue with a 
captive audience of patients with untreated HCV infection. To support the effectiveness of this strategy, 
we will use a validated protocol to identify and train peers at OTP sites to support HCV treatment 
engagement and reinfection prevention of PWUD recruited at these sites.  The interventions we 
propose to test will target barriers at different levels and thus impact multiple steps in the HCV care 
continuum from linkage to care to cure (Figure 1).  
 
 
 
 
 
 

 
 
 
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Figure 1: HCV Treatment Barriers 
 
 
 
2.2 
Clinical Hypothesis 
An HCV test and treat strategy, defined as immediate offer of and access to HCV treatment after testing 
HCV positive enhanced by peer support, will be associated with higher rates of HCV treatment initiation 
and cure compared to standard of care (SOC) referral to off-site HCV treatment. 
3 STUDY OBJECTIVES AND ENDPOINTS 
3.1 
Objectives 
The study aims to assess the effectiveness of an HCV test and treat strategy with peer enhancement 
compared to standard of care referral.  
 
3.2 
Primary Endpoint 
The primary effectiveness endpoint is: 
 
Treatment initiation: Proportion of participants who start HCV treatment (in initial test and treat arm 
versus standard of care referral arm) within 12 weeks of randomization. 

 
 
 
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3.3 
 Secondary Endpoints 
1) HCV treatment completion: Proportion of those initiating treatment who complete HCV treatment 
defined as taking more than 90% of prescribed treatment course by expected end of treatment date. 
2) SVR 12: Proportion of participants with HCV RNA <15 IU/ml between 10 and 36 weeks after end of 
treatment in each randomization arm. 
3) Time to HCV treatment initiation after randomization. 
 
3.4 
Exploratory Endpoints 
1) Impact of test and treat versus standard of care referral on proportion of participants with change in 
substance use assessed by self-reported drug use in the preceding 30 days and urine toxicology at 
recruitment screening, end of HCV treatment, and post-treatment weeks 12, 24, and 36. Participants 
who do not start HCV treatment will be assessed at weeks 12, 24, and 36 post-randomization. 
2) Impact of test and treat versus standard of care referral on subsequent substance use disorder 
treatment engagement-Proportion of expected weekly OTP visits actually attended, based on 
participant’s OTP treatment plan. 
3) Proportion of patients in the standard of care arm who are not offered treatment within 6 months (24 
weeks) of randomization.  
4) Proportion of patients in the standard of care arm who do not initiate treatment within 6 months (24 
weeks) of randomization and subsequently initiate HCV treatment after study cross over to 
intervention arm. 
5) Patient reported outcomes, quality of life measures, and patient satisfaction with test and treat 
model versus standard of care referral will also be assessed.  
6) Proportion of participants with grade 3 or greater adverse events (AEs) in test and treat model versus 
standard of care referral. 
 
4 INVESTIGATIONAL PLAN 
4.1 
Overall Study Design and Plan 
This is an open label, multicenter, phase IV randomized trial to assess the effectiveness of an HCV test 
and treat strategy with peer enhancement compared to standard of care referral.  
 
The study is designed to enroll approximately 124 HCV infected subjects at 4 drug treatment program 
sites in the US and 1 drug treatment program site in Canada.   
 

 
 
 
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We will also characterize the processes of implementation of peer supported on site HCV treatment at 
the drug treatment clinics including adoption, fidelity, drug treatment clinic staff acceptability, and drug 
treatment clinic workflow integration and congruence. 
Figure 2: Study Schema 
 
* Study laboratory testing (HCV RNA, CBC, CMP, HBsAg, BHcG) may be collected prior to randomization. 
 
Test and treat strategy with peer support: Consistent with the approach in substance use self-help 
groups such as narcotics anonymous, the intervention will include support for HCV treatment initiation 
and completion from true peers (PWUD who have previously engaged in HCV treatment). 
 
Peer Mentor selection and training: Many OTPs utilize peers as an element of substance use recovery. 
Each site will identify individuals with a history of drug use who have been treated for HCV and 
demonstrate good communication and interpersonal skills to serve as peers. These individuals may be 
referred to study staff by OTP staff. They will then be offered participation in the study and be 
consented to participate in the study as peers, and will undergo a tailored validated training (up to 5 
hours) developed and successfully utilized in the CHAMPS trial15. Trainings will include in-depth 
discussions of HCV, HCV treatment and prevention of reinfection and skill development such as effective 
mentoring, active listening skills, facilitation, the importance of confidentially, and harm reduction 
including overdose prevention. These trainings are divided into 5 modules which can be watched 
independently by peers. Modules are designed to be engaging with activities which the peer will 
complete during the module and then discuss with site research assistants during check-in sessions. 
Peers will be assessed to ensure they have mastered required competencies to function effectively as a 
peer prior to being permitted to serve in this role. 
 
In the event a peer drops out, sites will be asked to identify other peers who have successfully 
completed HCV treatment who are interested in participating in the study as a peer. They will then go 
through the training process and undergo evaluation to ensure that they have mastered the required 
*

 
 
 
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competencies prior to being permitted to serve as peer. 
 
The peers will meet and engage with participants in the test and treat strategy at the time of 
randomization, throughout treatment, and up to assessment of SVR 12. The key role of the peers will be 
to provide information, enhance motivation, and role model behavioral skills required for HCV 
treatment initiation, completion, and reinfection prevention.   
 
Standard of care referral: Referral to off-site partner site with provision of clinic information for 
scheduling. 
 
4.2 
Study Procedures 
4.2.1 Hepatitis C Diagnosis and Recruitment Screen   
Prior to study roll out, site investigators will meet with drug treatment center leadership to outline 
procedures for offering study participation to drug center clients. The OTP will facilitate HCV antibody 
testing and/or HCV RNA testing through rapid testing or phlebotomy. Prior to study enrollment, 
participants will complete an initial screening questionnaire, which will explore if the participant has 
previously been diagnosed with HCV, and if previously diagnosed, previously treated for HCV with oral 
direct-acting antiviral (DAA) therapy. Individuals who report previous HCV treatment with oral DAA 
therapy will not be eligible for study enrollment. Potential participants will also be asked about their 
current medications to ensure they are not currently taking any medication prohibited by the study (see 
Sections 5.1 and 5.3). Individuals who report taking a study-prohibited medication will not be eligible for 
study enrollment. These screening questions will be mixed with other questions to ensure that 
participants remain unaware of study eligibility criteria. Individuals who are HCV antibody or HCV RNA 
positive on testing and remain study eligible after completing the screening questionnaire will be 
offered enrollment into the study and if willing, go through the process of informed consent.   
 
4.2.2 Informed Consent 
Each participant must give consent according to local requirements after the nature of the study has 
been fully explained.  The informed consent form (ICF) that is used must be approved by the 
Institutional Review Board (IRB) and be in a language that the participant can read and understand. The 
informed consent should be in accordance with principles that originated in the Declaration of Helsinki, 
current International Conference for Harmonization (ICH) and Good Clinical Practice (GCP) guidelines 
and applicable regulatory including IRB policy and requirements. 
 
The participant will be given sufficient time to read the ICF and the opportunity to ask questions. After 
this explanation and before entry into the study, consent should be appropriately recorded. After having 
obtained the consent, a copy of the ICF must be given to the participant. 
 
4.2.3 Demographic and Medical History 
After signing consent, participant’s name, date of birth, age (calculated), sex, primary and secondary 
forms of contact, address, race, and ethnicity will be collected.  Medical history will be collected by 
participant interview. Participants will be asked to provide all medical history to the best of their 
recollection, and then will be asked specifically about the following medical history items that impact 

 
 
 
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eligibility: Presence of liver cirrhosis or history of decompensated liver disease or liver cancer, 
pregnancy, previous HCV treatment with oral DAAs, history of hepatitis B infection.  
 
4.2.4 Concomitant Medication Documentation 
All concomitant medications and supplements as of Day 0 will be recorded. 
 
4.2.5 Pregnancy Test 
All participants will be asked to provide information determining childbearing status. Females who are 
post-menopausal (absence of menses for 12 months or greater) or who have had a hysterectomy are 
considered not to be of childbearing potential. Any females not meeting these criteria are considered to 
be of childbearing potential and will have a point of care dipstick urine or serum beta human chorionic 
gonadotropin (HCG) test performed. Pregnant women will not be enrolled in this study. 
Females of childbearing potential will be cautioned against getting pregnant or attempting to get 
pregnant during this study. Requirements for ongoing contraception are noted in protocol section 5.2. 
 
4.2.6 Vital Signs 
Height, weight, temperature, pulse, respiratory rate and blood pressure will be collected at the study 
site.  
 
4.2.7 Patient Reported Outcomes (PRO) and Quality of Life (QOL) Measures  
We will utilize validated measures to assess patient reported outcomes and will also qualitatively assess 
satisfaction with HCV care received in both intervention and SOC arms. We will utilize the validated Eq 
5d-5l16, validated PHQ-817, GAD-718, AUDIT C19, modified addiction severity index, MOS social support 
scale, Health efficacy and HCV stigma scales. We will also qualitatively assess participant perception of 
their HCV care among a purposively sampled group of patients who did and did not initiate HCV 
treatment in intervention (n=20) and standard of care (n=20) across the five OTPs. Participants will be 
offered interviews starting approximately 6 months post-randomization. In-depth interview guides will 
be designed to focus on experiences with HCV treatment, barriers and facilitators of HCV treatment 
initiation and completion.  
 
4.2.8 Randomization 
Randomization will occur separately at each OTP. Randomization will take place on day 0 after 
recruitment screening activities have been performed and the Investigator or designee has determined 
that the participant is eligible based on information that is available.  Day 0 laboratory tests including 
blood HCV RNA, complete blood count (CBC), comprehensive metabolic panel (CMP), hepatitis B surface 
antigen (HBsAg), and urine/serum beta HCG, may not be available at the time of randomization and 
participants may be randomized without this information. Randomization will be built into the study 
REDCap database. It may not be known at screening whether participants have detectable HCV RNA or 
not. All participants will be randomized in a 1:1 ratio to test and treat strategy or standard of care 
referral. Participants who are found to have an HCV RNA that is not detectable, HbsAg positive or a 
platelet count that is <150,000 will not continue in the study, and will be referred to an offsite location 
for care.  
 

 
 
 
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4.2.9 Study Arms 
Intervention – Test and Treat strategy: This will consist of a meeting (in person, by phone or over video) 
with a trained peer mentor who will meet with the study participant after randomization to 
communicate information about HCV in a manner that takes into account an understanding of 
experiences with HCV and care access faced by people who use drugs, the potential harms of untreated 
HCV and the benefits of HCV treatment. 
 
Peer Training, Monitoring, and Quality Assurance. Peers will receive training modelled on our previous 
experience training peers for HCV treatment support. The training will be provided as modules. Topics to 
be addressed in the modules are: 1) Power of peer mentoring and key values including confidentiality 
and respect for all persons; 2) Tools for effective communication; 3) HCV disease and substance use 
disorder including importance of adherence to medications/visits; 4) Self-care in the peer-mentor role; 
5) review of patient tracking tools. Peers will also have an individual training session. Individual sessions 
will prepare the peer for their peer support role including building communication skills to enhance 
conversations to support HCV care engagement. Peers will be trained to improve their communication 
skills with a focus on: 1) providing accurate information; 2) working with patients on goal setting for HCV 
treatment adherence; and 3) identifying barriers to retention in care. We will ensure peers have 
demonstrated competency in all of their tasks through knowledge and performance assessments as 
judged through role-plays.   
 
Peer support and care coordination tasks. Peers will be responsible for maintaining contact with patients 
in the test and treat arm. They will also complete adherence and food use with medication surveys at 
weekly contacts. He or she will also communicate the need to return for results of follow up testing and 
follow through with recommended treatment. The Peer will also communicate to the patient the 
expected timing of follow up appointments at the drug treatment center and will offer support for the 
duration of HCV treatment. Up to 15 peers will be enrolled in this study.  
 
The treatment initiation visit at the drug treatment center will depend on the standard amount of time 
it takes to get results of laboratory testing back to the drug treatment center site. We expect this to be 
3-5 days. 
 
The peer will contact the patient 2 days before and the day before the scheduled appointment to 
remind that participant about the appointment. 
 
Peers will have a standard protocol for at least weekly phone contact with participants through post-
treatment week 12, and will be available to answer participant questions as needed. Peers will maintain 
a log of peer contact, which will be submitted to research program staff weekly. 
 
Peers will have access to drug treatment clinic staff for support with trouble shooting any arising 
matters. 
 
Peers will submit weekly logs of participant contact to the research program coordinator and meet as a 
group (both peers and research program coordinator at each site, either virtually or in person) to review 
best practices and address any issues or questions related to effective performance as a peer. 
 

 
 
 
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If the participant does not want to work with the assigned peer, they can choose not to receive peer 
services. 
 
HCV treatment initiation. At the treatment initiation visit, if still eligible for the study after all Day 0 
results are available (detectable HCV RNA, platelet count >150,000, not pregnant) the patient will be 
offered immediate initiation of HCV treatment. 
 
HCV treatment will be initiated at the drug treatment center. Participants will be provided a 4-week 
supply of glecaprevir/pibrentasvir (GLE/PIB) combination.  For patients who report living and other 
situations that pose barriers to safe storage of a 4-week supply of medications, individual drug 
treatment centers will develop processes for providing GLE/PIB in quantities that can be safely stored by 
the participant.  
 
At the treatment initiation visit, participants will be given a follow up appointment for 8 weeks after 
treatment initiation (expected end of treatment) with designated drug treatment center staff. 
 
Standard of Care Referral to Offsite Location: Participants randomized to standard of care arm will be 
referred to an offsite HCV treatment site.  
 
Using a signed release of medical information form, research staff will follow up with the referral site to 
see if the patient scheduled and subsequently attended an appointment and collect information on 
subsequent progress along the HCV care continuum. 
 
If the patient is confirmed to have scheduled the appointment, study staff will contact the evaluating 
physician to make them aware that the study may provide GLE/PIB for HCV treatment.  
 
Participants in the standard of care arm who do not initiate HCV treatment within 6 months (24 weeks) 
after randomization and still meet study eligibility criteria upon rescreen will be offered HCV treatment 
at the OTP site via rollover to the Intervention Arm. 
 
Any participant that does not clear HCV infection will be linked to repeat HCV treatment and care at an 
offsite HCV treatment location through standard of care. There are approved regimens available to treat 
patients who do not achieve cure with first line treatment. 
 
4.2.10 Intervention Fidelity Assessment 
Peers will maintain logs of contact with participants randomized to the intervention arm. Peers will 
submit weekly logs of participant contact to site study research program coordinators. 
 
4.2.11 Assessment of implementation outcomes 
The well validated Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) 
framework20 will be used to guide evaluation of implementation outcomes of peer enhanced HCV 
treatment at OTP sites using its dimensions; reach and effectiveness, which operate at the individual 
level of those intended to benefit; and adoption and implementation which focus on staff and setting 
levels. We will focus on acceptability of the peer enhanced drug treatment center based HCV test and 
treat strategy, barriers and facilitators of implementation success and congruence with drug treatment 

 
 
 
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clinic workflow. In-depth interviews will focus on exploring how peer supported drug treatment clinic 
based HCV treatment may become embedded in routine clinical practice in drug treatment settings. We 
will utilize a mixed methods assessment including quantitative survey data from patients (collected 
through clinical trial), and qualitative in-depth interviews (IDI) with drug treatment clinic leadership and 
staff (n=45) and program peers (n=15)  across five sites.  
 
Setting and population: The focus of this assessment is individuals implementing and being affected by 
implementation of peer-supported drug treatment clinic based HCV treatment. We will utilize the RE-AIM 
framework for this assessment. 
 
Table 1: Summary of Implementation Outcomes Using the RE-AIM Framework 
Component 
Research 
Question 
Assessment 
Method(s) 
Outcome(s) of 
Interest 
Sampling of 
qualitative interview 
content 
Reach 
Who received the 
peer enhanced 
drug treatment 
center based HCV 
test and treat 
intervention? 
Study data 
Patient in 
depth 
interviews 
(IDI)  
• Proportion of study 
participants who 
initiated HCV 
treatment. 
• Characteristics of 
those who  initiated 
vs. those who did not 
initiate HCV treatment 
Barriers and 
facilitators to HCV 
treatment initiation 
What components of 
the intervention 
were most effective 
(patients) 
Effectiveness 
What impact did 
the intervention 
have on 
outcomes? 
HCV 
treatment 
initiation  
(Study data)   
• Proportion of study 
participants who 
initiated HCV 
treatment in 
intervention 
compared to SOC arm. 
 -- 
Adoption 
Did the patients, 
peers and drug 
treatment center 
adopt the 
intervention? 
Study data, 
peer contact 
logs, OTP 
staff and 
peer surveys, 
IDI with 
providers, 
staff, peers 
• Frequency of 
contacts between 
peers and patients. 
• Proportion of 
patients who 
previously failed to 
and subsequently 
cross over and initiate 
HCV treatment 
 
Barriers and 
facilitators to 
adoption 
(intervention 
uptake), steps to 
enhance uptake;  
perceived need for 
intervention, 
perceived fit in 
current care 
structure ( peers, 
drug treatment clinic 
staff, clinic 
leadership)  
Implementation 
Was the 
intervention 
Standardized 
fidelity 
• Adherence to 
intervention protocols 
(Fidelity) 
Perceptions of the 
most effective 
components of the 

 
 
 
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4.2.12 Adjustments for COVID related restrictions 
Study specific activities including screening, consenting, survey administration will have the option of 
being performed remotely by phone or video visits with research staff.  All study activities that must be 
done in-person (sample collection, study medication dispensation) for participants in both arms may 
occur during the participant’s regularly scheduled OTP visits. No additional research-only visits to OTP 
will be needed. 
 
5 STUDY ACTIVITIES 
5.1 
Inclusion and exclusion Criteria 
Inclusion criteria: Participants must meet all of the following inclusion criteria to be eligible for 
participation  
 Ability and willingness of participant to provide written informed consent 
 Men and women age ≥18 to ≤70 years at study entry   
 HCV antibody positive/Detectable HCV RNA   
 HCV treatment naïve (no prior treatment with an approved or investigational oral DAA therapy) 
 Negative pregnancy test at screening or at the day of treatment initiation (females of 
childbearing potential only) 
 If co-infection with Human Immunodeficiency Virus (HIV) is documented, the subject must be 
anti-retroviral treatment (ART) naïve with CD4 T cell count >500 cells/mm3 OR on a stable ART 
regimen (containing only permissible ART – Raltegravir; dolutegravir; Rilpivirine; 
Elvitegravir/cobicistat; Tenofovir disoproxil fumarate; Tenofovir alafenamide; Emtricitabine; 
Lamivudine and/or Abacavir, bictegravir) 
 
Exclusion criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in this 
study 
 Women who are pregnant or breastfeeding, or considering becoming pregnant during the study 
and for 30 days after the last dose of study drug 
 Known allergy/sensitivity or any hypersensitivity to components of study drugs or their 
formulation 
 Current or history of decompensated liver disease (including but not limited to encephalopathy, 
variceal bleeding, or ascites) prior to study entry 
delivered as 
intended? 
assessment 
form, IDI 
• Dose frequency of 
peer contact with 
patient. 
• Frequency of HCV 
medication pick-up at 
OTP 
intervention (peers, 
providers, clinic staff, 
leaders),   

 
 
 
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 History of hepatocellular carcinoma (HCC) 
 Any history of active Hepatitis B or positive HBsAg test  
 Platelet count < 150,000/mm3  
 HCV RNA undetectable 
 History of clinically significant abnormalities or co-morbidities that make the subject an 
unsuitable candidate for this study, in the opinion of the investigator. 
 Women of childbearing potential that are not practicing at least one specified method of birth 
control (refer to Section 5.2) that is effective from Study Day 1 through at least 30 days after the 
last dose of study drug. 
 Subject is currently taking any of the following prohibited medications:   
• 
Red yeast rice (monacolin K), St. John's Wort 
• 
Carbamazepine, Dabigatran, efavirenz, phenytoin, pentobarbital, phenobarbital, primidone, 
rifabutin, rifampin  
 Subject is not able or willing to safely discontinue the prohibited medications or supplements 
listed below at least 14 days prior to the first dose of GLE/PIB: 
• 
Some HMG-CoA reductase inhibitors (including atorvastatin, lovastatin, or simvastatin) 
should not be taken with the study drug.  Subjects receiving these statins should either 
(a) switch to pravastatin or rosuvastatin at least 14 days or 10 half-lives (whichever is longer) 
prior to the first dose of study drug or (b) may interrupt statin therapy throughout the 
treatment period beginning at least 14 days or 10 half-lives (whichever is longer) prior to the 
first dose of study drug and until 14 days after the last dose of study drug, based on 
investigator's judgment.  If switching to or continuing pravastatin or rosuvastatin, it is 
recommended to reduce the pravastatin dose by 50% or limit the rosuvastatin dose to 5 mg 
QD when taking with the study drug. 
• 
Astemizole, cisapride, terfenadine 
• 
Ethinyl estradiol 
 
5.2 
Contraception Recommendations 
Contraception Requirements for Females: 
 
Postmenopausal is defined as: 
• 
Age > 55 years with no menses for 12 or more months without an alternative medical cause. 
 
If female, subject must be either post-menopausal, permanently surgically sterile (bilateral 
oophorectomy, bilateral salpingectomy or hysterectomy) or a woman of childbearing potential (WOCBP) 
and must practice at least one of the following methods of birth control, throughout the study including 
30 days after the last study drug dose is given. 
• 
Contraceptives and/or hormonal replacement therapies containing only progestins (such as 
those containing norethindrone, desogestrel, or levonorgestrel) or those containing progestins 

 
 
 
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with non-ethinyl estradiol estrogens (e.g., esterified or conjugated) associated with inhibition of 
ovulation initiated at least 1 month prior to study Baseline Day 1. 
• 
Bilateral tubal occlusion/ligation. 
• 
Intrauterine device (IUD). 
• 
Intrauterine hormone-releasing system (IUS). 
• 
Vasectomized sexual partner(s) (the vasectomized partner(s) provided the vasectomized partner 
has received medical assessment of the surgical success and is the sole sexual partner of the 
trial participant). 
• 
Male or female condom with or without spermicide. 
• 
Cap, diaphragm or sponge with spermicide. 
• 
A combination of male condom with either cap, diaphragm or sponge with spermicide (double 
barrier method). 
• 
True abstinence:  Refraining from heterosexual intercourse when this is in line with the 
preferred and usual lifestyle of the subject, (periodic abstinence [e.g., calendar, ovulation, 
symptothermal, post-ovulation methods] and withdrawal are not acceptable). 
 
For male study subjects no contraception is required. 
 
5.3 
Prohibited Medications and Therapy 
Subjects must not be taking any prohibited medications or supplements listed in Section 5.1 for at least 
14 days prior to the first dose of any study drug and not use these during the entire treatment period 
and for 14 days following discontinuation of study drug.    
 
Contraceptives and/or hormonal replacement therapies containing only progestins (such as those 
containing norethindrone, desogestrel, or levonorgestrel) or those containing progestin with non-ethinyl 
estradiol estrogens (e.g., esterified or conjugated) may be used with GLE/PIB at the discretion of the 
Investigator. 
 
5.4 
Prior and Concomitant Therapy 
The investigator should confirm that a concomitant medication/supplement can be safely administered 
with study drug.  Some medications may require dose adjustments due to the potential for drug-drug 
interactions (DDIs). 
 
Any medication/supplement or vaccine (including over-the-counter or prescription medicines, vitamins 
and/or supplements) that the subject is receiving from the time of signing the consent through the 
Treatment Period must be recorded in the electronic case report form (eCRF) along with the reason for 
use, date(s) of administration including start and end dates, and dosage information including dose, 
route and frequency.  The investigator should review all concomitant medications for any potential 
DDIs. 
 
Any questions regarding concomitant or prior therapy should be raised to the Sponsor Medical Contact. 

 
 
 
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5.5 
Withdrawal of Subjects and Discontinuation of Study 
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons including, 
but not limited to, the following:  
• 
Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the Investigator or the Sponsor Medical Director. 
• 
The Investigator believes it is in the best interest of the subject. 
• 
The subject requests withdrawal from the study. 
• 
Eligibility criteria violation was noted after the subject started study drug, when continuation of 
the study drug would place the subject at risk. 
• 
Introduction of prohibited medications or dosages when continuation of the study drug would 
place the subject at risk. 
• 
The subject becomes pregnant while on study drug and the investigator, after discussion with 
the subject, concludes that the benefit of continuing therapy does NOT outweigh the risk. 
• 
Subject is significantly non-compliant with study procedures, which would put the subject at risk 
for continued participation in the trial. 
• 
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the final status of the subject.  At a minimum (unless otherwise required by local 
regulations), 2 phone calls must be made and 1 certified letter must be sent and documented in 
the subject's source documentation. If a patient is not reachable by phone a letter will be sent 
or visit conducted to the address on file to reestablish contact with the patient. The letter/visit 
will alert the patient of study team efforts to reach them as well as provide the viable contact 
methods the patient may use to contact the study team.  
 
Sponsor may terminate this study prematurely, either in its entirety or at any site. The Investigator may 
also stop the study at his/her site if he/she has safety concerns.  If the study terminates for safety 
reasons, the sponsor will promptly notify the Investigator. 
 
Refer to Section 6.3 for additional discontinuation criteria relating to Toxicity Management. 
 
5.6 
Follow-Up for Subject Withdrawal from Study 
In order to minimize missing data for efficacy and safety assessments, subjects who prematurely 
discontinue study drug treatment should continue to be followed for all regularly scheduled visits, 
unless they have decided to discontinue the study participation entirely (withdrawal of informed 
consent).  Subjects should be advised on the continued clinical importance of their data even if they 
discontinue treatment with study drug early. 
 
If, during the course of study drug administration, the subject prematurely discontinues (D/C) study 
participation, the procedures outlined for the applicable Premature D/C Visit in the Schedule of Events 

 
 
 
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(Appendix A) should be completed.  Ideally, this should occur on the day of study drug discontinuation, 
but no later than 2 days after their final dose of study drug and prior to the initiation of any other anti-
HCV therapy.  However, these procedures should not interfere with the initiation of any new treatments 
or therapeutic modalities that the investigator feels are necessary to treat the subject's condition.  
Following discontinuation of study drug, the subject will be treated in accordance with the investigator's 
best clinical judgment.  All attempts must be made to determine the date of the last study drug dose 
and the primary reason for discontinuation of study drug or study participation.  The last dose of any 
study drug and reason for discontinuation will be recorded in the eCRF.   
 
If a subject is discontinued with an ongoing adverse event or an unresolved laboratory result that is 
significantly outside of the reference range, the investigator will attempt to provide follow-up until a 
satisfactory clinical resolution of the laboratory result or adverse event is achieved. 
5.7 
Study Drug 
5.7.1 Identity of Study Drug 
Information about the study drug to be used in this study is presented in Table 2. 
 
Table 2: Identity of Study Drug 
Study Drug  
Manufacturer 
Mode of 
Administration 
Dosage Form 
Strength 
Glecaprevir/pibrentasvir  
AbbVie 
Oral 
Film-coated 
tablet 
100 mg/40 
mg 
 
Three tablets of GLE/PIB combination will be taken daily and should be taken at the same time each day.  
The study drug must be taken with food.  
 
Glecaprevir/pibrentasvir combination tablets will be provided.  
 
5.7.2 Packaging, labelling, storage and accountability of clinical trial supplies  
Glecaprevir/pibrentasvir will be provided by AbbVie and should be dispensed under the supervision of 
the investigator or a qualified member of the study team including drug treatment center staff, or by a 
hospital/clinic pharmacist.  
 
Participants will not be required to return any unused study drug. Study drug may not be relabeled or 
reassigned for use by other participants.  
 
A designated person at the study site must receive the study drug shipment. That person must check 
that the supplies are in good condition and are complete as per the shipping records. Study drugs must 
be stored in a secure location with limited access. The study drug must only be dispensed according to 
the protocol and records must be kept detailing supplies received, dispensed to the participant, 
returned from the participant and returned to the sponsor or destroyed at site, as applicable. 
Study staff must not open or count clinical trial supplies prior to dispensing. 

 
 
 
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Study drug should be stored in a securely locked area, accessible only to authorized site personnel. To 
ensure the stability of the study drug and to ensure proper product identification, the drug product 
should not be stored in a container other than the container in which they are supplied. 
 
Glecaprevir/pibrentasvir should be stored according to the product label.  
 
Participants should ensure that the study drug is stored securely away from children and in dry 
conditions. The study drug should be kept in the original packaging. 
 
5.8 
Protocol Deviations 
The Investigator is responsible for complying with all protocol requirements, written instructions and 
applicable laws regarding protocol deviations.  Protocol deviations are prohibited except when 
necessary to eliminate an immediate hazard to study subjects.  If a protocol deviation occurs (or is 
identified), the Investigator is responsible for notifying IRB, regulatory authorities (as applicable) and the 
Sponsor. 
 
5.9 
Study Labs 
The study-specific laboratory tests being conducted are HCV RNA, complete blood count (CBC), 
comprehensive metabolic panel (CMP), hepatitis B surface antigen (HBsAg), urine drug testing, and 
urine/serum beta HCG. These tests are able to be submitted to the study site’s local laboratory of 
choice. 
The chemistry tests required in the CMP are alanine aminotransferase (ALT/SGPT); albumin:globulin 
(A:G) ratio; albumin, serum; alkaline phosphatase, serum; aspartate aminotransferase (AST/SGOT); 
bilirubin, total; BUN; BUN:creatinine ratio; calcium, serum; carbon dioxide, total; chloride, serum; 
creatinine, serum; eGFR calculation; globulin, total; glucose, serum; potassium, serum; protein, total, 
serum; sodium, serum. 
The drug screen analytes required in the urine drug test are amphetamine; barbiturate; 
benzodiazepines; cocaine or benzoylecgonine; fentanyl; methadone; opiates; oxycodone/oxymorphone; 
phencyclidine (PCP); propoxyphene; tramadol. 

 
 
 
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6 SAFETY CONSIDERATIONS  
6.1 
Known and Potential Risks to Participants 
6.1.1 Collection of Blood 
Collection of blood may cause slight discomfort, pain, bleeding or bruising at the collection site. Rarely, 
fainting or infection may occur. Only properly trained clinical staff will draw blood. The amount of blood 
collected is the minimal amount for proper analysis. 
 
6.1.2 Internet-Based Data Collection 
Data collection will be performed using the REDCap electronic data collection (EDC) and storage hosted 
by Johns Hopkins University. All data in REDCap will be de-identified. Each site will maintain a record of 
which participant corresponds to participant numbers assigned by REDCap. This file will be password 
protected if electronic or kept in a locked location if in the participant binder. Only authorized personnel 
requiring a password will be permitted to enter data. There is risk, although minimal, of unauthorized 
persons obtaining confidential information. 
 
In brief, the REDCap Consortium consists of 84 institutional partners from CTSA, GCRC, RCMI and other 
institutions, in which JH is an active participant. It was developed by CTSA partners at Vanderbilt, with 
the goal of enabling investigator research through the establishment of a more user-friendly database 
system. This consortium supports two secure web-based applications designed to enable data capture 
for research studies. The software contains an intuitive interface for collecting data with data validation 
commands, allows for automated export procedures to statistical packages (e.g. SAS) and provides 
advanced features that allow for branching logic, file uploading, etc. The system itself is supported on 
MySQL, an open source database similar to SQL/Oracle, and operates on a web-based system. All 
servers are backed-up at each data center (institution) and include password protection to provide 
enhanced security while maintaining accessibility via the internet. 
 
6.2 
Complaints and Adverse Events 
6.2.1 Data safety monitoring  
This study implements on-label use of the medication GLE/PIB for persons with Hepatitis C Virus whose 
current infection has not been exposed to prior direct-acting antiviral (DAA) therapy. There are not 
expected to be changes to the known safety and efficacy data for this agent. Thus, there will be no 
formal data safety monitoring board. The site investigator will determine grade (Division of AIDS (DAIDS) 
Table for Grading the Severity of Adult and Pediatric Adverse Events) and relatedness to GLE/PIB for all 
adverse events and if any serious unexpected adverse events arise, the site investigator will discuss and 
decide with the study Principal Investigator whether this protocol should be suspended.  
 
6.2.2 Medical Complaints/Adverse Events and Serious Adverse Events 
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 

 
 
 
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laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product. 
 
An AE can result from use of the drug as stipulated in the protocol or labeling, as well as from accidental 
or intentional overdose, drug abuse, or drug withdrawal.  Any worsening of a pre-existing condition or 
illness is considered an AE.  Worsening in severity of a reported AE should be reported as a new AE.  
Laboratory abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, meets protocol specific 
criteria (see Section 6.3 regarding toxicity management) and/or if the investigator considers them to be 
AEs. 
 
Adverse event reporting will follow the requirements outlined below. Adverse events will also be 
recorded and tracked in a safety monitoring database by the investigators. Serious adverse events 
(SAEs) will be reported to the Institutional Review Board according to IRB guidelines and to AbbVie via 
the Johns Hopkins University Transplant Oncology and Infectious Diseases Clinical Research Center 
(TOID CRC). 
 
All Grade 3 or higher and all SAEs related to the use of GLE/PIB in intervention arm or prescribed DAA 
course in SOC arm will be collected.  Thus, AEs and SAEs will only be collected from the time of first DAA 
dose to 30 days after completion of DAA course. 
 
All Grade 3 or higher AEs and all SAEs will be reviewed by the principal investigator as they occur in a 
timely manner. All AEs related or possibly related to GLE/PIB will be reported by the site to the TOID CRC 
within 72 hours of the site being made aware via the REDCap EDC system.  All SAEs will be reported to 
the TOID CRC via the REDCap EDC system within 24 hours of the site being made aware. Notification of 
all SAEs will be made to AbbVie by the TOID CRC via email within 24 hours of entry into REDCap.  
 
6.2.3 Adverse Event Relationship to Study Drug 
For the purpose of medical management, all Grade 3 and 4 AEs and laboratory abnormalities that occur 
during the study must be evaluated by the Investigator.  All AEs and laboratory abnormalities deemed 
"clinically significant" based on the medical judgment of the Investigator will be managed and followed 
to a satisfactory clinical resolution.   
 
The investigator will use the following definitions to assess the relationship of the adverse event to the 
use of study drug: 
 
Reasonable Possibility – After consideration of factors including timing of the event, biologic plausibility, 
clinical judgment, and potential alternative causes, there is sufficient evidence (information) to suggest 
a causal relationship. 
 
No Reasonable Possibility – After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is insufficient evidence 
(information) to suggest a causal relationship. 
 

 
 
 
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6.2.4 Pregnancy 
While not an AE, pregnancy in a study subject should be monitored. Information regarding a pregnancy 
occurring up to 30 days after end of treatment in a study subject and the outcome of the pregnancy will 
be collected. 
 
In the event that a positive result is obtained on a pregnancy test for a subject or a subject reports 
becoming pregnant during the Treatment Period, the administration of study drug may be continued at 
the Principal Investigator's discretion after discussion with the subject, if the benefit of continuing study 
drug is felt to outweigh the potential risk.  If a subject is discontinued, the subject will be monitored for 
SVR in the Post-Treatment Period. 
 
6.3 
Toxicity Management 
The management of specific AEs and laboratory parameters is described below. This includes the 
following laboratory abnormalities:  
 
If a subject experiences a post-baseline increase in alanine aminotransferase (ALT) to > 3 × 
upper limit of normal (ULN), which is also > 2 × baseline value, the subject, should have a 
confirmatory ALT measurement performed. 
 
If, the ALT increase is confirmed to be > 3 × ULN, which is also > 2 × baseline value, the 
recommendations below, should be followed: 
• 
Evaluate for alternate etiology of ALT elevation; document in the source, update the medical 
history and concomitant medications eCRF (if applicable), and obtain Anti-hepatitis A virus 
immunoglobulin M (HAV IgM), Anti-hepatitis A virus total (HAV Total), Anti-hepatitis B core 
(HBc) IgM, Anti-HBc Total, Anti-Hepatitis B surface (HBs), Hepatitis B Virus (HBV) DNA, 
HBsAg, Anti-hepatitis E virus immunoglobulin M (HEV IgM), Anti-hepatitis E virus 
immunoglobulin G (HEV IgG) and HEV RNA, and other additional tests, as appropriate.  
• 
Manage the subject as medically appropriate. 
• 
Repeat ALT, aspartate aminotransferase (AST), total and fractionated bilirubin, alkaline 
phosphatase and international normalized ratio (INR) within 1 week.  Repeat liver 
chemistries as indicated until resolution. 
Discontinue study drug if any of the following is observed at any time: 
• 
ALT level is ≥ 3 × ULN and total bilirubin of > 2 x ULN without initial findings of cholestasis 
(elevated serum alkaline phosphatase) in the absence of an alternate etiology including 
another drug capable of causing the observed injury. 
• 
Increasing direct bilirubin or INR or onset of symptoms/signs of hepatitis. 
• 
At the discretion of the investigator. 
 
Alternate management of ALT increases is permitted with approval of the Sponsor Medical Director. 
 

 
 
 
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6.4 
Product Complaint 
A Product Complaint is any complaint related to the biologic or drug component of the product.  
 
For a product this may include, but is not limited to, damaged/broken product or packaging, product 
appearance whose color/markings do not match the labeling, labeling discrepancies/inadequacies in the 
labeling/instructions (example: printing illegible), missing components/product, or packaging issues. 
 
Product Complaints concerning the investigational product must be reported to the TOID CRC via the 
REDCap EDC system within 24 hours of the study site's knowledge of the event. Notification of product 
complaints will be made to AbbVie by the TOID CRC via email within 24 hours of the site reporting the 
complaint. Product Complaints occurring during the study will be followed up to a satisfactory 
conclusion. 
 
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE 
7.1 
Statistical and Analytical Plans 
The primary analysis for the effectiveness of the test and treat strategy versus standard of care referral 
for HCV treatment initiation will be assessed using a logistic regression model and a two-sided Type 1 
error rate (alpha) of 0.05. Since participants will be recruited from drug treatment programs at which 
they are receiving ongoing treatment for substance use disorder, we expect low rates of lost to follow 
up (10%).  
 
7.2 
Definition for Analysis Populations 
All analyses will be conducted with a modified intention to treat of approach, which excludes 
randomized participants who were found on testing to have an undetectable HCV RNA, HBsAg positive 
or a platelet count <150,000. 

 
 
 
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7.3 
Statistical Analyses 
7.3.1 Primary Analysis 
Sample Size and Power Consideration Estimation 
 
The planned sample size for the trial is  124  participants enrolled and randomized in a 1:1 ratio to test 
and treat strategy versus Standard of Care referral. This sample size is based on preliminary data from 
the CHAMPS study, which offered free onsite HCV treatment to HIV infected patients at an urban 
infectious disease clinic and achieved a 70% HCV treatment initiation rate.15 Data from community-
based sites including the AIDS linked to the intravenous experience study suggest an HCV treatment 
start rate of 30% among community based people who use drugs enrolled in the oral DAA era in 
Baltimore21. Given differences in HCV treatment policies and restrictions, HCV treatment rates were 
estimated to be up to 55% in other cities prior to the COVID-19 pandemic. HCV treatment uptake rates 
reduced during and post-COVID 19. We estimate HCV  treatment uptake between 30-50% in different 
cities, averaging  40%. Using these data points as estimates for treatment initiation in the test and treat 
arm (70%) and the treatment uptake in the referral arm (40%) power calculations are as follows. With a 
total sample size of 124 participants, we have 85% power at an alpha of 0.05 to detect a statistically 
significant difference in treatment initiation in the test and treat strategy versus the standard referral 
arm. The sample size of 124 allows for 110 completers should there be a  ~10% drop out rate. If there is 
no drop out then the total enrollment of the HCV infected participants will be 124. We continue to 
expect that the treatment uptake will be 70% with the proposed test and treat interventions. Our 
proposed sample size of 55 completers per group (62 per group including possible drop outs) is 
adequate to distinguish between the hypothesized 70% uptake and the 40% non-intervention arm 
uptake with 85% power at the p = 0.05 threshold.  
 
 
7.3.2 Statistical analyses 
All analyses will be conducted with a modified intention to treat of approach, which excludes 
randomized participants who were found on testing to have an undetectable HCV RNA, HBsAg positive 
or a platelet count <150,000. Our primary analysis will be logistic regression analyses. Statistical 
inference will use a two-sided Type 1 error rate of 0.05 and 95% confidence intervals.   
 
7.3.3 Secondary outcomes  
1) HCV treatment completion: Proportion of those initiating treatment who complete HCV treatment 
defined as taking more than 90% of prescribed treatment course by expected end of treatment date. 
2) SVR 12: Proportion of participants with HCV RNA <15 IU/ml between 10 and 36 weeks after end of 
treatment in each randomization arm. 
Analysis for secondary outcomes 1 and 2 will be logistic regression analyses. 
3) Time to HCV treatment initiation after randomization. 

 
 
 
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For secondary outcome 3, a time to event outcome, we will perform survival (Kaplan Meier) analysis for 
time to HCV treatment initiation. 
 
Analysis of adverse event data will primarily be descriptive. Adverse event data will be compared 
between randomization arms using Fisher’s exact Test.  
 
7.3.4 Sensitivity analysis for missing data 
We expect very low missingness of data in our results. We will explore the demographic and clinical 
characteristics comparing persons with full and incomplete follow-up, and try to define the mechanism 
of missingness with the input of study staff about clinical operations. This experiential input is necessary, 
because there is no data-driven mechanism to decide on non-ignorability of missing data.  For Missing 
Not At Random sensitivity analysis, we will use multiple imputation methods to test the robustness of 
our results. 
 
7.3.5 Qualitative analysis 
Analysis. Transcripts of audio-recordings from in-depth interviews will be uploaded into MAXQDA 
software22 for the purposes of coding and analysis. Our approach to the qualitative data will involve 
thematic analysis and employ both inductive and deductive coding techniques.23,24 We will first develop 
an a priori code book that reflects key analytic dimensions of the RE-AIM framework. New themes that 
emerge from the data will be analyzed through a grounded theory approach, allowing for themes to 
emerge and ensuring that the knowledge assembled from the observational data is not subjected to the 
themes solely established through the in-depth interview guide. Qualitative analysis will proceed by first 
exploring broad patterns and experiences of patients, peers, drug treatment clinic leadership and staff, 
and then assessing possible similarities and differences in experiences between staff (including different 
ages, sex, and level of training) and the 5 different sites. Two coders will conduct open coding on three 
transcripts to develop initial coding schemes. After discussion and development of a combined draft 
scheme, two more interviews will be coded, and these will be further discussed and inform a final 
coding scheme which will be developed. Through weekly meetings, a team approach to data analysis will 
be employed, whereby different analysts provide feedback on emerging interpretations and check 
emerging categories against the raw data. In this way, an “audit trail” will be used to help ensure 
trustworthiness of findings, gather input from multiple perspectives, and enhance reliability. 
 
Mixed methods. The qualitative data will provide context to the quantitative data and in-depth 
understanding of barriers and facilitators to program implementation in the local context. We will merge 
and integrate quantitative and qualitative data. The qualitative themes will be compared to survey 
results, combined and jointly displayed. We will create a matrix relating qualitative themes to 
quantitative variables. Findings will inform future programming efforts. 
 

 
 
 
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8 ETHICS 
8.1 
Independent Ethics Committee/Institutional Review Board (IEC/IRB) 
The JHM IRB will provide IRB oversight for all domestic sites.  Expert review of the research protocol is 
carried through the work of the JHM IRB to ensure that research is well designed and likely to yield 
generalizable knowledge, and that risks are both commensurate with benefit and accurately disclosed to 
research participants. This protocol, the ICF, and any subsequent modifications will be reviewed and 
approved by the JHM IRB or ethics committee responsible for oversight of the study. A signed consent 
form will be obtained from the participant (or legal representative or person with power of attorney for 
participants who cannot consent for themselves). The consent form will describe the purpose of the 
study, the procedures to be followed, and the risks and benefits of participation. A copy of the consent 
form will be given to the subject, or legal representative and this fact will be documented in the 
participant’s record. 
 
8.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, ICH guidelines, applicable regulations and 
guidelines governing clinical study conduct and the ethical principles that have their origin in the 
Declaration of Helsinki.  Responsibilities of the Investigator are specified in Appendix D.  
 
8.3 
Subject Confidentiality 
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or codes. 
 
8.4 
Johns Hopkins University Transplant Oncology and Infectious Diseases Clinical Research Center 
(TOID CRC) 
8.4.1 Protocol and Consent Version Control 
The TOID CRC will maintain protocol and consent version control. The umbrella protocol will not be 
modified by any site other than the TOID CRC. All amendments and other pertinent protocol information 
are sent to the participating sites via email, as a PDF document, after approval by JHM IRB.  The TOID 
CRC will maintain a Regulatory Database for this study that will record the protocol and informed 
consent version, JHM IRB approval and expiration date, participating site distribution date and 
confirmation of receipt via the Protocol Signature Page that will be signed and dated by the site’s 
Principal Investigator and returned to the TOID CRC.  
 
8.4.2 Data Collection and Management 
Study data will be entered via eCRFs using the REDCap EDC system.  The REDCap EDC is a secure web-
based electronic data capture system. Each person entering data in the EDC system must complete a 
training. After verification of appropriate training, the Data Center will issue a unique username and 
password. The username and password will create an audit trail each time data is entered. Routine 
remote and/on-site monitoring will be conducted to verify timely and accurate entry of data.  

 
 
 
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CONFIDENTIAL INFORMATION 
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie. 
 
8.4.3 Protocol Events and Deviations 
Sites will report all SAEs to the TOID CRC by entering the SAE directly into REDCap.  When the site enters 
a SAE into the study database, an automatic email will be generated and sent to the TOID CRC Safety 
Contact. The TOID CRC will then review the case to ensure completeness and clarity, and confirm 
seriousness and attribution. In addition, all sites will follow their local reporting requirements. Domestic 
sites will also be responsible for reporting protocol events and/or protocol deviations that meet JHM IRB 
prompt reporting directly to the JHM IRB: 
 
https://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/organization_policies
/prompt_reporting_policy.html 
8.4.4 Annual Enrollment Data 
Annual enrollment data will be directly reported to the JHM IRB by the TOID CRC.   
 
9 SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION 
The Investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH GCP, and applicable local regulatory requirement(s). 
 
10 DATA QUALITY ASSURANCE 
Sponsor will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.  
 
11 COMPLETION OF THE STUDY 
The end-of-study is defined as the date of the last subject's last visit. 
 
 
 

 
 
 
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CONFIDENTIAL INFORMATION 
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12 REFERENCES 
1. 
Ly KN, Hughes EM, Jiles RB, Holmberg SD. Rising Mortality Associated With Hepatitis C Virus in the United 
States, 2003-2013. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 
May 15 2016;62(10):1287-8. doi:10.1093/cid/ciw111 
2. 
Organization WH. Global health sector strategy on viral hepatitis, 2016-2021- The first of it's kind. 2016. 
WHO, Geneva.  
3. 
Zibbell JE, Asher AK, Patel RC, et al. Increases in Acute Hepatitis C Virus Infection Related to a Growing 
Opioid Epidemic and Associated Injection Drug Use, United States, 2004 to 2014. Am J Public Health. Feb 
2018;108(2):175-181. doi:10.2105/AJPH.2017.304132 
4. 
(CDC) CfDCaP. Viral Hepatitis Statistics and Surveillance—United States, 2018. 2019. 
https://www.cdc.gov/hepatitis/statistics/2018surveillance/HepC.htm 
5. 
Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who 
inject drugs: results of systematic reviews. Lancet. Aug 13 2011;378(9791):571-83. doi:10.1016/S0140-
6736(11)61097-0 
6. 
Zeremski M, Zibbell JE, Martinez AD, Kritz S, Smith BD, Talal AH. Hepatitis C virus control among persons 
who inject drugs requires overcoming barriers to care. World journal of gastroenterology : WJG. Nov 28 
2013;19(44):7846-51. doi:10.3748/wjg.v19.i44.7846 
7. 
Graf C, Mucke MM, Dultz G, et al. Efficacy of Direct-acting Antivirals for Chronic Hepatitis C Virus Infection 
in People Who Inject Drugs or Receive Opioid Substitution Therapy: A Systematic Review and Meta-analysis. 
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. May 23 
2020;70(11):2355-2365. doi:10.1093/cid/ciz696 
8. 
Grebely J, Oser M, Taylor LE, Dore GJ. Breaking down the barriers to hepatitis C virus (HCV) treatment 
among individuals with HCV/HIV coinfection: action required at the system, provider, and patient levels. The 
Journal of infectious diseases. Mar 2013;207 Suppl 1:S19-25. doi:10.1093/infdis/jis928 
9. 
Falade-Nwulia O IR, Merkow A,  Sulkowski M,  Niculescu A, Olsen Y, Stoller K, Thomas D, Latkin C,  Mehta 
H. . Barriers and Facilitators of hepatitis C treatment uptake among people who inject drugs enrolled in opioid 
treatment programs in Baltimore. Journal of substance abuse treatment. 2019; 
10. 
Mehta SH, Thomas DL, Sulkowski MS, Safaein M, Vlahov D, Strathdee SA. A framework for understanding 
factors that affect access and utilization of treatment for hepatitis C virus infection among HCV-mono-infected and 
HIV/HCV-co-infected injection drug users. Aids. Oct 2005;19 Suppl 3:S179-89.  
11. 
Mehta SH, Lucas GM, Mirel LB, et al. Limited effectiveness of antiviral treatment for hepatitis C in an 
urban HIV clinic. Aids. Nov 28 2006;20(18):2361-9. doi:10.1097/QAD.0b013e32801086da 
12. 
Mehta SH, Genberg BL, Astemborski J, et al. Limited uptake of hepatitis C treatment among injection drug 
users. Journal of community health. Jun 2008;33(3):126-33. doi:10.1007/s10900-007-9083-3 
13. 
McGowan CE, Monis A, Bacon BR, et al. A global view of hepatitis C: physician knowledge, opinions, and 
perceived barriers to care. Hepatology. Apr 2013;57(4):1325-32. doi:10.1002/hep.26246 
14. 
AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. 
http://www.hcvguidelines.org. Accessed December 9,2020.  
15. 
Ward KM, Falade-Nwulia O, Moon J, et al. A Randomized Controlled Trial of Cash Incentives or Peer 
Support to Increase HCV Treatment for Persons With HIV Who Use Drugs: The CHAMPS Study. Open Forum Infect 
Dis. Apr 2019;6(4):ofz166. doi:10.1093/ofid/ofz166 
16. 
Janssen MF, Pickard AS, Golicki D, et al. Measurement properties of the EQ-5D-5L compared to the EQ-5D-
3L across eight patient groups: a multi-country study. Qual Life Res. Sep 2013;22(7):1717-27. doi:10.1007/s11136-
012-0322-4 
17. 
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. Journal of 
general internal medicine. Sep 2001;16(9):606-13. doi:10.1046/j.1525-1497.2001.016009606.x 
18. 
Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the 
GAD-7. Arch Intern Med. May 22 2006;166(10):1092-7. doi:10.1001/archinte.166.10.1092 

 
 
 
p. 30 of 36 
STUDY B20-237| RAPID HCV Version 5.2 
CONFIDENTIAL INFORMATION 
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie. 
19. 
Bradley KA, Bush KR, Epler AJ, et al. Two brief alcohol-screening tests From the Alcohol Use Disorders 
Identification Test (AUDIT): validation in a female Veterans Affairs patient population. Arch Intern Med. Apr 14 
2003;163(7):821-9. doi:10.1001/archinte.163.7.821 
20. 
Glasgow RE, Vogt TM, Boles SM. Evaluating the public health impact of health promotion interventions: 
the RE-AIM framework. Am J Public Health. Sep 1999;89(9):1322-7. doi:10.2105/ajph.89.9.1322 
21. 
Falade-Nwulia O, Gicquelais RE, Astemborski J, et al. Hepatitis C treatment uptake among people who 
inject drugs in the oral direct-acting antiviral era. Liver international : official journal of the International 
Association for the Study of the Liver. Oct 2020;40(10):2407-2416. doi:10.1111/liv.14634 
22. 
VERBISoftware. MAXQDA 2020 [computer software]. 2019. 
23. 
Miles MH SJ. Qualitative Data Analysis. Sage Publications; 2013. 
24. 
J M. Qualitative Research Design: an interactive approach. Sage Publications; 2013. 
 

 
 
 
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CONFIDENTIAL INFORMATION 
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APPENDIX A. SCHEDULE OF EVENTS (ALL PARTICIPANTS) 
  
Recruitment 
Screen 
Day 0 
Treatment 
Day 1 
Treatment 
Week 4 
End of 
Treatment 
-0d/+30d 
Post-Treatment 
Week 12 
-14d/+30d 
Post-Treatment 
Week 24 
-14d/+30d 
Post-Treatment 
Week 36 
-14d/+30d 
Early 
D/C 
Visit 
Eligibility Reviewa 
X 
X 
  
  
  
  
  
  
  
Vital Signsb 
  
X 
  
  
  
  
  
  
  
Demographics 
  
X 
  
  
  
  
  
  
  
Medical History 
  
X 
  
  
  
  
  
  
  
Concomitant Medicationsc 
  
X 
  
  
X 
  
  
  
  
Randomization 
  
X 
  
  
  
  
  
  
  
Referral to HCV Treatment 
(SOC Arm Only)  
  
X 
  
  
  
  
  
  
  
AE/SAE Collectiond 
  
  
→ 
→ 
→ 
  
  
  
  
Laboratory Testing 
  
  
  
  
  
  
  
  
  
HBsAg 
  
X 
  
  
  
  
  
  
  
Pregnancy Teste 
  
X 
  
  
  
  
  
  
  
CBCf 
  
X 
  
  
  
  
  
  
  
HCV RNAg 
  
X 
  
  
X 
X 
  
X 
X 
CMP 
  
X 
  
  
X 
X 
  
  
X 
Urine Toxicology Screen 
  
X 
  
  
X 
X 
X 
X 
  
Dried Blood Spot 
  
X 
  
  
X 
X 
X 
X 
X 
Surveys/Questionnaires 
  
  
  
  
  
  
  
  
  
Study Survey 
  
X 
  
  
X 
X 
X 
X 
  
PRO/QOL Measures 
  
X 
  
  
X 
X 
X 
X 
  
Intervention Arm Only 
  
  
  
  
  
  
  
  
  
Peer Contacth 
  
X 
→ 
→ 
→ 
→ 
  
  
X 
Study Drug Dispensationi 
  
  
X 
X 
  
  
  
  
  
aIncluding documentation of HCV infection (antibody) and treatment history. 
bIncluding height, weight, temperature, pulse, respiratory rate, and blood pressure. 
cAll medication (including supplements and over-the-counter) will be collected. 
dAE/SAE collection starts with initiation of DAAs, continues through 30 days after last DAA dose. 
eFor all participants of childbearing potential. Urine or serum test. 
fWith or without differential. 
gCLIA certified. 
hPeer contact to occur weekly and as needed between visits until SVR 12. Contact can be in-person, via phone, or video. 
iStudy drug can be dispensed in smaller amounts more frequently if participant is unable to maintain 4-week supply at home.

 
 
 
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STUDY B20-237| RAPID HCV Version 5.2 
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APPENDIX B. SCHEDULE OF EVENTS (PARTICIPANTS WHO DO NOT START HCV TREATMENT BY WEEK 12 AFTER RANDOMIZATION IN 
EITHER ARM) 
For participants who have not initiated treatment by Week 12 after randomization, complete the following.  
  
Week 12 after 
randomization 
-14d/+30d 
Week 24 after 
randomization 
-14d/+30d 
Week 36 after 
randomization 
-14d/+30d 
Week 56 after 
randomization 
-14d/+30d 
Laboratory Testing 
 
 
 
 
Urine Toxicology Screen 
X 
X 
X 
X 
Dried Blood Spot 
X 
X 
X 
X 
HCV RNAe 
 
X 
 
X 
Surveys/Questionnaires 
  
  
  
 
Study Survey 
X 
X 
X 
X 
PRO/QOL Measures 
X 
X 
X 
X 
Rescreen for SOC Participants to 
Rollover to Intervention Arm 
 
 
 
 
Eligibility Review 
 
X 
 
 
Vital Signsa 
 
X 
 
 
Concomitant Medicationsb 
 
X 
 
 
HBsAg 
 
X 
 
 
Pregnancy Testc 
 
X 
 
 
CBCd 
 
X 
 
 
CMP 
 
X 
 
 
Peer Contactf 
 
→ 
 
 
 
aIncluding height, weight, temperature, pulse, respiratory rate, and blood pressure. 
bAll medication (including supplements and over-the-counter) will be collected. 
cFor all participants of childbearing potential. Urine or serum test. 
dWith or without differential. 
eCLIA certified. 
fParticipant will meet with peer on date of rescreen. If participant is still eligible for rollover to Intervention Arm after rescreening labs result, peer contact to occur weekly and 
as needed between visits until SVR 12. Contact can be in-person, via phone, or video. 

 
 
 
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APPENDIX C. STUDY SPECIFIC ABBREVIATIONS AND TERMS 
Abbreviation 
Definition 
AASLD 
American Association for the Study of Liver Diseases 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ART 
Anti-retroviral treatment 
AST 
Aspartate aminotransferase 
CBC 
Complete blood count 
CMP 
Comprehensive metabolic panel 
DAA 
Direct-acting antiviral agent 
DAIDS 
Division of AIDS 
D/C 
Discontinuation 
DDI 
Drug-drug interaction 
DNA 
Deoxyribonucleic acid 
eCRF 
Electronic case report form 
EDC 
Electronic Data Collection 
GCP 
Good Clinical Practice 
GLE 
Glecaprevir 
HAV 
Hepatitis A virus 
HAV IgM 
Hepatitis A virus immunoglobulin M 
HBc 
Hepatitis B core 
HBs 
Hepatitis B surface 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCC 
Hepatocellular carcinoma 
HCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HEV 
Hepatitis E virus 
HEV IgG 
Hepatitis E virus immunoglobulin G 
HEV IgM 
Hepatitis E virus immunoglobulin M 
HIV 
Human immunodeficiency virus 

 
 
 
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ICF 
Informed consent form 
ICH 
International Conference for Harmonization 
IDI 
In-depth interview 
IDSA 
Infectious Diseases Society of America 
IEC 
Independent ethics committee 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IU 
International units 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
mL 
Milliliter 
OTP 
Opioid treatment program 
PIB 
Pibrentasvir 
PRO 
Patient Reported Outcomes 
PWUD 
People who use drugs 
QOL 
Quality of life 
RE-AIM 
Reach, Effectiveness, Adoption, Implementation, and Maintenance framework 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SOC 
Standard of care 
SUD 
Substance use disorder 
SVR 12 
Sustained virologic response 12 weeks post dosing 
ULN 
Upper limit of normal 
WHO 
World Health Organization 
WOCBP 
Woman of childbearing potential 

 
 
 
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APPENDIX D. RESPONSIBILITIES OF THE INVESTIGATOR 
Clinical research studies sponsored by AbbVie are subject to the International Conference for 
Harmonisation (ICH) Good Clinical Practices (GCP) and local regulations and guidelines governing the 
study at the site location.  In signing the Investigator Agreement, the investigator is agreeing to the 
following: 
1. Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, current 
protocol and Operations Manual, and making changes to a protocol only after notifying AbbVie 
and the appropriate Institutional Review Board (IRB)/Independent Ethics Committee (IEC), except 
when necessary to protect the subject from immediate harm. 
2. Personally conducting or supervising the described investigation(s). 
3. Informing all subjects, or persons used as controls, that the drugs are being used for investigational 
purposes and complying with the requirements relating to informed consent and ethics 
committees (e.g., IEC or IRB) review and approval of the protocol and its amendments. 
4. Reporting complaints that occur in the course of the investigation(s) to AbbVie. 
5. Reading the information in the Investigator's Brochure/safety material provided, including the 
instructions for use and the potential risks and side effects of the investigational product(s). 
6. Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments. 
7. Maintaining adequate and accurate records of the conduct of the study, making those records 
available for inspection by representatives of AbbVie and/or the appropriate regulatory agency, 
and retaining all study-related documents until notification from AbbVie. 
8. Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical protocol and all of its amendments. 
9. Reporting promptly, all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others, to the appropriate individuals (e.g., coordinating investigator, 
institution director) and/or directly to the ethics committees and AbbVie. 
10. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s). 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Name of Principal Investigator (printed or typed) 
 
 
 
 

 
 
 
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APPENDIX E. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Previous Protocol Versions 
Protocol 
Date 
Version 1.0 
Initial version. 
19-FEB-2021 
Version 2.0 
Removed washout period of some prohibited medications from eligibility criteria. 
Added language specifying research labs to be conducted. 
12-APR-2021 
Version 3.0 
Removed rollover to Appendix A Schedule of Events for participants who initiate 
HCV treatment after Week 12 post-randomization. 
22-JUL-2021 
Version 4.0 
Updated study sites. 
Clarified secondary endpoints. 
Clarified study definition of 6 months. 
Clarified that study screening labs can happen prior to randomization. 
Clarified study definition of prior HCV treatment. 
Added timing for participant IDI. 
Added information for determining participant is lost to follow up. 
Updated urine toxicology testing requirements. 
Expanded study visit windows. 
Added Week 56 visit for participants who do not start HCV treatment by Week 12. 
08-MAR-2022 
Version 5.1 
Updated sample size from 250 to 124. 
Added language to primary analysis section to clarify updated sample size.  
Updated primary analysis section to reflect modification of a statistical calculation.    
 
14-DEC-2022