Conditions: Hepatitis C HIV-1-infection Liver Diseases
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 400
Healthy volunteers: no

Brief summary:
To achieve global hepatitis C virus (HCV) elimination by 2030, 80% of the \~71 million people with chronic HCV infection will need to be treated, necessitating simplification of treatment delivery and associated laboratory monitoring without compromising efficacy or safety. The COVID-19 pandemic has further highlighted the need for innovative models of health care delivery that minimize face-to-face patient-provider contact. The purpose of this study was to evaluate the feasibility, safety, and efficacy of a minimal monitoring (MINMON) strategy to deliver interferon- and RBV-free, pan-genotypic DAA therapy to treat active HCV in HCV treatment naïve participants.

Detailed description:
This study evaluated the feasibility, safety, and efficacy of a minimal monitoring (MINMON) strategy of delivering interferon- and ribavirin (RBV)-free, pan-genotypic direct-acting antiviral (DAA) therapy to treat active hepatitis C virus (HCV) in HCV treatment naïve participants, with or without HIV-1 co-infection, and with no evidence of decompensated cirrhosis.

The MINMON intervention included four components: 1) No pre-treatment HCV genotyping; 2) Entire 12-week treatment course (84 tablets) dispensed to participants at study entry; 3) No scheduled on-treatment laboratory monitoring or clinic visits prior to SVR evaluation scheduled 24 weeks following entry; 4) Remote contact with participants at week 4 for adherence counseling and locator update, and week 22 for scheduling of SVR visit and locator update.

At study entry, all participants received a single-tablet, fixed-dose combination (FDC) of sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks.

The trial was designed to accrue 400 adult participants who may be co-infected with HIV-1 (limited to no more than 200 participants), and whose liver disease state is either no cirrhosis (defined by Fibrosis-4 score) or compensated cirrhosis (defined by Fibrosis-4 and Child-Turcotte-Pugh (CTP) scores, and limited to no more than 80 participants). Accrual from research sites in the United States was limited to no more than 132 participants.

The study proceeded in two steps: Step 1: MINMON intervention and Step 2: post-MINMON follow up.

During Step 1 (MINMON intervention), participants were contacted remotely at week 4 to inquire about study medication adherence and confirm locator information, and again at week 22 to schedule the sustained virologic response (SVR) evaluation and confirm locator information. Unplanned in-person clinic visits before week 22 were permissible to address common treatment toxicities that could not be managed remotely. The primary efficacy outcome measure, sustained virologic response (SVR), was evaluated starting at the week 24 study visit. Early discontinuation of treatment did not alter the timing of the SVR evaluation. If the week 24 visit was missed, SVR could be evaluated at any time up to 76 weeks following study entry.

Following SVR evaluation, participants entered Step 2 for two additional post-SVR evaluation study visits at weeks 48 and 72. Participants were contacted remotely at weeks 42 and 68 to schedule such visits. The schedule of additional post-MINMON evaluation visits were dependent on the week of Step 2 entry.

In version 1 of the study, total study duration was up to 76 weeks. Due to the COVID-19 Pandemic, the window of the week 72 visit was extended for participants who completed SVR evaluations and registered to Step 2 to October 31, 2020 for US sites and to February 28, 2021 for non-US sites. This extension did not alter the window for SVR evaluation.

All scheduled in-clinic study visits included a physical exam, blood collection, and collection of plasma samples. For participants able to become pregnant, pregnancy testing was conducted at screening, entry, and at any in-clinic visit during Step 1 if pregnancy was suspected. Liver Elastography was an optional evaluation.

Arms:
arm 1: Participants received Sofosbuvir/Velpatasvir (SOF/VEL \[Tradename: Epclusa®\]) tablet for 12 weeks with a minimal monitoring (MINMON) strategy for 24 weeks

Interventions: intervention 1: Sofosbuvir/Velpatasvir (SOF/VEL) intervention 2: Minimal Monitoring (MINMON) Strategy
Intervention descriptions: intervention 1: 400/100 mg fixed-dose combination (FDC) tablet administered orally once daily with or without food. intervention 2: MINMON Strategy:

1. No pre-treatment HCV genotyping
2. Entire treatment course (84) tablets of SOF/VEL administered to participants at study entry
3. No scheduled on-treatment laboratory monitoring or clinic visits
4. Remote contact with participants at week 4 and week 22

Protocol document:
ICF_000.pdf: 
 
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INFORMED CONSENT 
 
DIVISION OF AIDS  
 
AIDS CLINICAL TRIALS GROUP (ACTG) 
 
 
TITLE: 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a 
Minimal Monitoring Strategy to Deliver Pan-genotypic Ribavirin-
free HCV Therapy to HCV Infected Populations who are HCV 
Treatment Naïve with Evidence of Active HCV Infection: The 
MINMON Study 
 
SHORT TITLE 
FOR THE STUDY:  
A5360 FINAL Version 1.0, 01/10/18, Monitoring SOF/VEL in 
Treatment Naïve, HCV Participants with Active Infection 
 
PROTOCOL NO.: 
A5360  
 
WIRB® Protocol #20180421 
 
SPONSOR: 
The National Institute of Allergy and Infectious Diseases (NIAID) 
 
INVESTIGATOR: 
Roger Bedimo, MS, MD, FACP 
 
 
 
 
 
 
 
STUDY RELATED 
PHONE NUMBER(S): 
Roger Bedimo, MS, MD, FACP 
 
 
 
 
INTRODUCTION 
 
You are being asked to take part in this research study because you have been infected with 
hepatitis C virus (HCV, a virus that affects the liver), and have not been treated before for HCV. 
You may also be infected with human immunodeficiency virus (HIV, the virus that causes AIDS). 
You may have compensated liver cirrhosis, which means that the liver is damaged, but is still 
working. This study is sponsored by the National Institutes of Health. The doctor in charge of 
this study at this site is: Dr. Roger Bedimo.  Before you decide if you want to be a part of this 
study, we want you to know about the study. 
 
This is a consent form. It gives you information about this study. The study staff will talk with you 
about this information. You are free to ask questions about this study at any time. If you agree to 
take part in this study, you will be asked to sign this consent form. You will get a copy to keep. 
 


 
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WHY IS THIS STUDY BEING DONE? 
 
Currently, people who are infected with HCV are often closely monitored by medical staff. This 
requires patients to come to the clinic at least five times for visits, medication refills, and blood 
tests over a 12-week course of treatment. These guidelines are based on older HCV 
medications that had more side effects and were less successful at curing HCV than the 
medications used in this study. New HCV medications can cure 95 out of 100 infected persons 
who receive treatment. The medication that is provided in this study is approved by the US FDA 
for use in persons infected with HCV and coinfected with HCV/HIV. In large clinical trials, the 
side effects reported by study participants were comparable to a placebo (no medicine). 
 
This study is being done to see if a minimal monitoring approach is effective and safe when 
providing HCV treatment. The minimal monitoring approach will require fewer study visits and 
lab tests with no medication refills. This study is trying to see whether taking an HCV treatment 
with fewer clinic visits and laboratory tests can cure just as many people as the standard 
approach that uses more visits and laboratory tests. We will compare the results of this study 
with what we have observed in other studies using a standard approach. 
 
People are considered cured of HCV if the HCV virus cannot be detected in the blood 12 weeks 
after they have completed HCV treatment. This is called a sustained virologic response (SVR). 
 
This study will measure the amount of HCV virus in your blood at entry, week 24, week 48, and 
week 72. The study staff will share these results with you. If the HCV virus is detectable in your 
blood at week 24 or after, the study staff will let you know, and help you find a health care 
provider who can discuss your future treatment options. You can become re-infected with HCV 
after you are cured. The study staff will discuss with you how to remain HCV free after your 
treatment is completed. 
 
The study will also examine the convenience to you and the cost to cure a person of HCV using 
this minimal approach. 
 
HOW MANY PEOPLE WILL BE IN THIS STUDY? 
 
About 400 people (men and women age 18 years and older) will take part in this study. 
 
WHERE IS THIS STUDY BEING DONE? 
 
This study will take place across the world and will include participants from the US and non-US 
sites. 
 
HOW LONG WILL I BE IN THIS STUDY? 
 
You will be in this study for up to 72 weeks.  
 
WHAT DO I HAVE TO DO IF I AM IN THIS STUDY? 
 
If you decide to join this study and meet the study requirements after the screening visit, you will 
be enrolled into the study, unless enrollment has been closed to the subgroup(s) as described 
below.   
 


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*After a person has successfully completed treatment for HCV, there is a period when HCV viral 
load in the blood is so low that even the most sensitive test cannot detect the virus. If this period 
of “undetectability” lasts for 12 weeks in a row after the end of treatment, it is called SVR 
(sustained virologic response). 
 
Everyone who enters the study will take a fixed-dose combination of sofosbuvir/velpatasvir 
(SOF/VEL), which will be provided by the study. Anti-HIV drugs will not be provided by the 
study. 
 
While you are in this study, you will need to be seen in the clinic about 5 times. The longest visit, 
which will be your enrollment visit, could take up to 2 hours. Study staff will tell you about how 
long each visit will be. You may need to come to the clinic more often if you have side effects. 
More information about the study tests is given below. During the study, you will get the results 
from any routine tests that are done during the study and relevant to your care when they are 
available. 
 
If you do not enroll into the study 
If you decide not to take part in this study or if you do not qualify to take part in this study, we 
will still use some of your information. As part of the screening visit, some demographic (for 
example, age, sex, gender, race), clinical (for example, disease condition, diagnosis), and 
laboratory (for example, CD4+ T-cell count, HCV and HIV viral load) information is being 
collected from you so that ACTG researchers may see if there are patterns or common reasons 
why people do not join a study. 
 
Required Blood Tests 
Your blood will be drawn from a vein in your arm and used to measure your HCV viral load (the 
amount of HCV virus in your blood), to measure levels of certain hormones (chemical 
messengers in your blood), to see if the hepatitis B virus (HBV; another virus that affects your 
liver) is in your body, and for routine safety tests and metabolic tests (to test how your body 
uses the food that you eat). If you are a woman able to become pregnant, you will have a 
pregnancy test at the screening and entry visits and at later study visits if you think you might be 
pregnant. If you are infected with HIV, you will have blood drawn to measure your HIV viral load 
(the amount of HIV virus in your blood) and your CD4+ cell counts (these are cells in your blood 
that fight infection). You will be told the results of these tests when they become available.  
 
Some of your blood will also be stored (with no information that will identify you) and used for 
HCV genotyping (a test to see the genetic makeup of the HCV virus) and sequencing (a test to 
check for the pattern/code of the genetic makeup of the HCV virus) for this study. HCV 
genotyping and sequencing are used to see which genotype of HCV you are infected with. 
Since these stored samples will be tested in the future, the results will not be available to you. 
 
Blood will also be collected and stored for future testing at the end of the study. Some of your 
blood samples may be shipped and/or stored outside of the country from which they are 
collected. 
 


 
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Genetic (the message in your DNA) testing 
If you agree, your blood will be drawn and used to examine different genes (pieces of your 
DNA). Results of testing done on these samples may not be given to you because they will be 
done in the future. If you do not agree to have genetic testing done, then the amount of blood 
drawn for future testing will be less (up to 20 mL less). 
 
Please initial below if you agree to have any of your blood used for ACTG-approved future 
unspecified genetic testing. You may change your mind at any time and your samples will be 
destroyed. 
 
 
 YES 
 
 NO 
 
Optional Tests 
If you agree, any blood left over after all required study testing is done may be stored (with no 
information that will identify you) and used for future ACTG-approved research. These blood 
samples may be stored for an unknown period of time. Results of testing done on these 
samples may not be given to you because they will be done in the future. 
 
Please initial below if you agree to have any of your leftover blood used for future ACTG-
approved research. You may change your mind at any time and reasonable efforts will be made 
to destroy your samples, though this may not always be possible. 
 
 
 YES 
 
 NO 
 
A5360 Study Visits 
The study staff can answer any questions you have about individual study visits, the evaluations 
that will occur, or how long each visit will be. The table below can be used as a quick reference 
for you, along with the explanations that follow. 
 
I. 
Appendix Table 1: Study Schedule 
 
Evaluation or 
test 
Scre
ening 
Entry 
Post-Entry Visits 
Unplanned 
Visits 
(Entry-
Week 24) 
Week 
4 
Week 
22 
Week 
24/SVR 
Evaluati
on 
Week 
42 
Week 
48 
Week 
68 
Week 
72 
Consent & 
Contact 
Information 
Collected 
 
 
 
 
 
 
 
 
 
 
Documentation 
of HCV, HIV, & 
Cirrhosis Status  
 
 
 
 
 
 
 
 
 
 
Liver 
Elastography (if 
available) 
 
 
 
 
 
 
 
 
 
 
Physical Exam 
 
 
 
 
 
 
 
 
 
(if 
indicated) 


 
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Evaluation or 
test 
Scre
ening 
Entry 
Post-Entry Visits 
Unplanned 
Visits 
(Entry-
Week 24) 
Week 
4 
Week 
22 
Week 
24/SVR 
Evaluati
on 
Week 
42 
Week 
48 
Week 
68 
Week 
72 
Medical & 
Medication 
History 
 
 
 
 
 
 
 
 
 
 
Blood Samples 
Collected (for 
laboratory 
testing) 
 
 
 
 
 
 
 
 
 
(if 
indicated) 
Blood Samples 
Stored (for later 
testing) 
 
 
 
 
 
 
 
 
 
(if 
indicated) 
Pregnancy Test  
 
 
 
 
(if 
suspecte
d) 
 
 
 
 
(if 
suspected) 
Pregnancy 
Prevention 
Counseling 
 
 
 
 
 
 
 
 
 
 
Cirrhosis 
Counseling 
 
 
 
 
 
 
 
 
 
 
HCV Risk-
reduction 
Counseling 
 
 
 
 
 
 
 
 
 
 
Adherence 
Counseling 
 
 
 
 
 
 
 
 
 
 
Questionnaires 
 
 
(via 
remote 
contact
) 
 
 
 
 
 
 
 
Study Drugs 
Distribution  
 
 
 
 
 
 
 
 
 
 
Locator 
Information 
 
 
 
 
 
 
 
 
 
 
Remote Contact 
With 
Participants 
Outside of 
Study Visits 
 
 
 
 
 
 
 
 
 
 
 
II.  
Description of Study Visits 
 
Screening 
After you have read and signed the consent form, you will be asked questions about 
your health, medical history, and medication history. You will have a complete physical 
exam to check your vitals (temperature, pulse, respiration rate, and blood pressure) and 
several tests, including blood tests, to make sure that you qualify to join the study. You 
will have your height and weight recorded. 


 
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Up to 42 mL of blood will be drawn during this visit. You will have blood drawn for HCV 
RNA testing. Some of the blood taken will be shipped to a testing lab and some of the 
blood will be stored for future testing. Your HCV infection and how long you have been 
infected will be confirmed. Your HIV infection and cirrhosis status will also be evaluated. 
 
If you are a woman able to become pregnant, you will have a blood draw or urine 
collected for pregnancy testing. You may not continue with the screening process if your 
pregnancy test is positive. If you are able to become pregnant or to impregnate a 
partner, you will receive pregnancy prevention counseling. 
 
Entry 
If all of the results from your screening tests show that you are eligible, you will be 
enrolled in the study. You will be asked about your health and the medications you are 
taking. You will also have a brief physical exam to check your vitals (temperature, pulse, 
respiration rate, and blood pressure). You will have your weight recorded. 
 
Up to 51 mL of blood will be drawn during this visit. You will also have additional 
samples collected and stored for later testing. If you are a woman able to become 
pregnant, you will be asked to provide a blood or urine sample for pregnancy testing. 
You may not enroll in the study if your pregnancy test result is positive. 
 
If available at the site, liver elastography (scan of your liver) will be performed. This is 
described below in more detail. If you had a liver elastography done as part of standard 
care, this measurement will be recorded but it is not required for enrollment into the 
study. 
 
You will be asked for your primary preferred contact information as well as a second 
contact (spouse, friend, neighbor, etc.) in order for the study staff to reach you 
throughout the study. This is known as locator information. If you are not able to be 
reached through the primary contact information, then the study staff will try to reach you 
through the second contact you provide. 
 
At this visit, you will be given your study drugs. The study staff will give you enough 
study drugs to last 12 weeks (3 months). Study staff will watch you take your first dose 
before leaving the site. You can take the study medication (SOF/VEL) with or without 
food. You will receive adherence education and counseling on the study drug, as 
described below. You will be given instructions on how to take the study medication and 
what to do if you forget to take it. You will also receive a flier with information on two 
types of other medications (proton pump inhibitors and H2 inhibitors [e.g., heartburn 
medication]) that you should not take while taking study medication. 
 
You will be asked to complete questionnaires that asks how you are doing and feeling, if 
you went to the hospital within the past 4 weeks, and if you use any substances such as 
alcohol, cigarettes, and other drugs. If you have compensated cirrhosis, you will also 
receive counseling for your cirrhosis, as described below. If you are able to become 
pregnant or to impregnate a partner, you will receive pregnancy prevention counseling. 
You will also receive HCV risk-reduction counseling and adherence counseling, as 
described below. 


 
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Post-entry visits 
Since you will be given enough study drugs to last you for 12 weeks of the treatment 
period, you will not need to come back to the clinic until week 24 (3 months later). Study 
staff will contact you by the preferred contact at weeks 4 and 22 to update your contact 
(locator) information and at week 4, to collect information about whether you are taking 
your study medication. If study staff are unable to reach you after two tries, they will try 
to reach you via your second contact. While you are taking the study drug, if you are not 
feeling well or have any questions about the study medication, you should contact the 
study site directly at 
 (24 hours). 
 
All participants will be seen post-treatment at week 24. If you miss the week 24 visit, you 
may come back to the site to have your SVR status checked any time after week 24, up 
until week 72. Following your SVR status check, you will be followed through week 72. 
You will need to make two more visits to the site -- one at week 48 and one at week 72, 
which is Part 2 of the study. These visits will last about 1-1½ hours each. 
 
At the week 4 remote contact, you will be asked how you are doing with taking your 
study medication. At the week 24/SVR evaluation visit, you will be asked how you did 
with taking your study medication. 
 
At weeks 24, 48, and 72, you will have blood samples collected for routine safety tests 
and for a few required blood tests (HCV RNA). Up to 76 mL of blood will be drawn during 
each of these visits. You will also have additional samples collected and stored for later 
testing. You will be asked about your health and any changes in your medicines since 
your last visit. You will have your weight recorded. You will be asked to complete 
questionnaires that asks how you are doing and feeling, if you went to the hospital within 
the past 4 weeks, and if you use any substances such as alcohol, cigarettes, and other 
drugs. 
 
Based on other tests done, the study staff will calculate different scores that will measure 
liver and kidney function and cirrhosis status. If you have compensated cirrhosis, you will 
also receive counseling for your cirrhosis, as described below. 
 
If available at the study site where you were enrolled, you will have a liver elastography 
done at weeks 24, 48, and 72. 
 
You will receive HCV risk-reduction counseling, as described below. If you have 
compensated cirrhosis, you will also receive counseling for your cirrhosis, as described 
below. 
 
Unplanned visits 
If you have any side effects during the treatment period, you must contact the study site. 
The study staff may require you to come in to the study site for an in-person evaluation. 
It is possible samples are collected for routine safety laboratory tests, or stored for future 
testing. If suspected, pregnancy testing and counseling will be done up to week 22. Up 
to 52 mL of blood could be drawn during this visit. 
 


 
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If you come to the study site for an unplanned visit, you will be asked to complete 
questionnaires that asks how you are doing and feeling, and if you went to the hospital 
within the past 4 weeks. 
 
 
Early discontinuation 
There are two types of discontinuation (stopping study treatment or leaving the study 
early). If at any point in the study, you want to discontinue study treatment or discontinue 
the study, you must contact the site immediately. 
 
1. Stop study treatment early 
 
You or your doctor may decide to stop the study medication that you began at entry. 
 
If you must stop taking the study medication early, the study doctor may ask you to 
stay in the study and come in for the scheduled visits and tests. 
 
2. Leave study early 
 
You or your doctor decides that you will no longer stay in the study or you are 
notified the study is stopped early. 
 
III. 
Description of Study Evaluations 
 
Consent and contact information collected 
After you read the consent form and have had a chance to ask questions about the 
study, you will sign the consent form if you want to continue the screening process. 
 
Documentation of HCV, HIV, and cirrhosis status 
Study staff will check your medical records for the availability of test results for HCV, 
HIV, and cirrhosis. If these results are not available, then you will have these tests done 
as part of the screening visit. 
 
Liver Elastography 
At entry, a liver elastography measurement (if available) will be recorded. A liver 
elastography is an easy, simple, and safe ultrasound procedure that measures the 
stiffness of the liver by placing a small probe over the area of the liver while you lie on 
your back. 
 
Clinical Assessments 
You will have the following clinical evaluations in this study: 
 
Physical examination 
You will have a physical exam. At screening, the study staff will check the different areas 
of your body such as head, neck, eyes, ears, nose, throat, mouth and tongue, chest 
(excluding breasts), heart, abdomen, skin, hair, nails, and muscles and joints. The study 
staff will also check your vital signs such as temperature, pulse, blood pressure, and 
respiratory rate. Your height and weight will be recorded. After screening, the physical 
exam will be more limited and based on symptoms or problems that you are 
experiencing. Your weight will be recorded. 


 
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Medical and medication history 
You will be asked questions about your health and about any medicines you have taken 
or are taking now. At week 24/SVR evaluation visit, you will be asked about any signs or 
symptoms that you are experiencing and any changes in other medications that you 
have had since your last visit. 
 
Sample collections and laboratory testing 
You will have the following samples collected and tested in this study: 
 
Blood collected 
Blood will be taken from a vein in your arm for various tests during the study. 
 
Stored blood 
Additional blood will also be collected from you and stored for testing at the end of the 
study. 
 
Pregnancy test 
If you are a woman who is able to become pregnant, you will have blood or urine taken 
for pregnancy testing at screening and entry. After you enter the study, you will have 
blood drawn or urine collected for pregnancy testing, if pregnancy is suspected up to 
week 22. 
 
Pregnancy prevention counseling 
All participants in the sexually reproductive age group will be counseled on family 
planning options for the duration of treatment (12 weeks). There is limited data on the 
safety of this medication during pregnancy and risk to the baby. Female participants who 
become pregnant during the course of treatment will be required to contact the site 
immediately and come in for a study visit as soon as possible. 
 
Cirrhosis Counseling 
If you have compensated cirrhosis, you will be counseled by study staff on managing 
your cirrhosis. Even though you may be cured of HCV, you will still have cirrhosis. 
 
HCV Risk-reduction Counseling 
You will be counseled by study staff on how HCV can be passed onto others and how to 
reduce your risk for HCV reinfection. HCV risk-reduction counseling will be done at 
entry, and weeks 24/SVR evaluation, 48, and 72. Study staff will talk with you about how 
you could become reinfected with HCV after being cured and ways to decrease risk of 
re-infection. 
 
Adherence Counseling 
You will get some adherence counseling from the study staff. The study staff will explain 
to you in detail how to take your study medication and help you find ways to take the 
medication correctly. 
 
Questionnaires 
You will be asked to complete a questionnaire that will ask how you are feeling and how 
you are doing with your daily activities. If you had stayed at a hospital or been to an 


 
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emergency room, you will be asked to complete a questionnaire when you come in for 
your visits at entry, weeks 24/SVR evaluation, 48, 72, and unplanned visits (if any). You 
will also be asked about substance use such as alcohol, cigarettes, and other drugs at 
your entry and weeks 24/SVR evaluation, 48, and 72 visits. 
 
See remote contact section below for information on what questions will be asked during 
the week 4 and 22 remote contacts. 
 
Study drugs distribution and storage 
You will be given a 12-week supply of study medication at entry. Study staff will watch 
you take your first dose, before you leave the site. You will be asked to store the study 
medication as instructed on the medicine bottle label.  
 
If you lose your study medication, you will be able to return to the site and receive 
replacement medication (one-time replacement only). 
 
Locator Information 
Study staff will ask you about the best way to reach you when they need to contact you 
remotely at weeks 4, 22, 42, and 68. They will also ask you for a second way to contact 
you (for example, through a spouse or friend) if they are unable to reach you. 
 
Remote contact with participants outside of study visits 
Study staff will contact you using your preferred method at week 4 to ask questions 
about adherence information (if you are taking your study drug), to update your contact 
information, and to remind you to return to the site to have your SVR status checked at 
week 24. 
 
During Part 1 of the study while you are taking the study (HCV) medication, you will be 
asked at week 4 if you are currently taking your study medication. 
 
At week 22, study staff will contact you to schedule your week 24 visit to have your SVR 
status checked and to update your contact information. 
 
During Part 2 of the study, after the week 24 visit, you will be contacted using your 
preferred remote method at weeks 42 and 68 to update contact information, if needed, 
and remind you of your upcoming study visits at weeks 48 and 72. 
 
WHY WOULD THE DOCTOR TAKE ME OFF THIS STUDY EARLY? 
The study doctor may need to take you off the study early without your permission if: 
 
• 
The study is cancelled. 
• 
Your doctor thinks the study is no longer in your best interest. 
• 
The site investigator thinks that you are at significant risk of failing to comply with the 
requirements of the protocol.  
 
The study doctor may also need to take you off the study drugs without your permission if: 
 
• 
You become pregnant. 
• 
You are breastfeeding. 


 
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• 
Continuing the study drugs may be harmful to you. 
• 
You need a treatment that you may not take while on the study. 
 
If I have to permanently stop taking study drugs through the study, or once I leave the study, 
how can I get study drugs? 
If you must permanently stop taking SOF/VEL before the study is over, the study staff will talk 
with you about other options. 
 
After you have finished the study, you will not be able to get SOF/VEL through the study. 
 
WHAT ARE THE RISKS OF THE STUDY? 
 
Risks of Social Harm 
Although the study site will make every effort to protect your privacy and confidentiality, it is 
possible that others could find out that you are participating in this study and that social harm 
may result (because you could become labeled as being infected with HCV and/or HIV). For 
example, you could be treated unfairly or discriminated against by family members, friends, 
and/or the community. 
 
Risks of Drawing Blood 
Drawing blood may cause some discomfort, lightheadedness, bleeding, swelling, or bruising 
where the needle enters the body, and in rare cases, fainting, or infection. 
 
Risks of Study Drug 
The study drug (SOF/VEL) is relatively safe and in controlled clinical trials it was found to have a 
safety profile similar to a placebo (no medicine). The most common side effects you may 
experience are headache, nausea, vomiting, fatigue and diarrhea. 
 
SOF/VEL has limited drug interactions with HIV medications with the exception of three HIV 
medications- efavirenz, tenofovir, and tipranavir/ritonavir. If you are taking any of these 
medications, your doctor will talk to you about these interactions in detail and what symptoms to 
look out for. Your doctor may modify your HIV medications after discussing it with you so that 
you can be included in this study. 
 
If you have been infected with Hepatitis B and do not have immunity, there is a minor risk of 
reactivation of the virus.  Please discuss this with your study doctor. 
 
SOF/VEL also has some interactions with other types of medications. There is risk of slow 
heartbeat if you also take amiodarone (a medication to help control heart rate). While you are on 
the study, you will be instructed not to take any of the prohibited medications (for example, 
heartburn medication mentioned earlier). The study staff will explain the prohibited and 
precautionary medications and discuss alternative options if you must take any of these 
concomitant medications. 
 
There is a risk of serious and/or life-threatening side effects when non-study medications are 
taken with the study drugs. For your safety, you must tell the study doctor or nurse about all 
medications you are taking before you start the study and also before starting any new 
medications while on the study. Also, you must tell the study doctor or nurse before enrolling in 
any other clinical trials while on this study. 


 
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Other Risks 
There is a risk that your stored samples may be misused. There are laws against this kind of 
misuse, but they may not fully protect you. The chance that this will happen is considered small 
because of the security taken with your samples. 
 
Your genetic information is unique to you. There is a risk in genetic research that someone 
using your samples may identify you. However, this risk is very small, but may increase with the 
progress of science. Researchers will inform you of any newly identified risks. 
 
If you are cured of your HCV, you could still become infected again with HCV. You can get HCV 
from coming in contact with blood and/or sexual fluid that is infected with HCV. 
 
ARE THERE RISKS RELATED TO DELAYING HIV THERAPY? 
 
You are not required to be on HIV medications to enter this study. If you are not on HIV 
medications at the time of your HCV infection and you and your doctor do not think you need to 
start HIV medications, we will not exclude you from the study. We also do not recommend 
delaying HIV medications for entry into the study if your doctor feels they are medically 
necessary. Although the dosing period of the HCV medication is short (84 days), a delay in 
necessary HIV medications could allow for progression of HIV disease, which can increase your 
risk of opportunistic infections and long-term after effects of HIV infection. If you have any 
concerns about these risks, we suggest that you discuss them with your medical provider. 
 
ARE THERE RISKS RELATED TO PREGNANCY? 
 
The drugs or drug combinations in this study have not been studied extensively in pregnancy. If 
you are having sex that could lead to pregnancy, you must agree not to become pregnant or to 
impregnate your partner while you are taking the study medication and for 6 weeks after 
stopping study medication. Note that if you become pregnant, study drug will be stopped and 
you will be asked to remain on the study. If you think you may be pregnant at any time during 
the study, tell your study staff right away. Pregnancies occurring on study will be reported to the 
Antiretroviral Pregnancy Registry, and study staff will request permission from you to obtain 
additional information after the baby is born. 
 
Because of the risk involved, you must use at least one method of birth control that you discuss 
with the study staff. You must continue to use at least one method as long as you are taking 
study medication and for 6 weeks after stopping study medication. You must agree to one or 
more of the birth control methods listed below: 
 
• 
A condom (male or female) with or without a spermicide 
• 
Diaphragm or cervical cap with or without spermicide 
• 
An intrauterine device (IUD) 
• 
Tubal ligation 
• 
Hormone-based contraceptives 
 
Male and female participants not of reproductive potential are not required to use 
contraceptives. 
 


 
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Some of the methods listed above may not prevent the spread of HIV to other people. If you are 
also infected with HIV, you should discuss your contraceptive choices with your health care 
provider to choose the best way for you to both prevent pregnancy as required by this study and 
to prevent the spread of HIV to your partner. 
 
Male participants should not donate sperm while on study treatment and for six weeks after 
stopping study medication. 
 
ARE THERE BENEFITS TO TAKING PART IN THIS STUDY? 
 
If you take part in this study, there may be a direct benefit to you. The study is designed to treat 
your HCV infection with an approved study medication and you may be cured of your HCV. It is 
also possible that you may receive no benefit from being in this study. Information learned from 
this study may help others who have HCV and/or HIV. 
 
WHAT OTHER CHOICES DO I HAVE BESIDES THIS STUDY? 
 
Instead of being in this study, you have the choice of: 
 
• 
treatment with prescription drugs currently available to you 
• 
treatment with other experimental drugs, if you qualify 
• 
no treatment 
 
Please talk to your doctor about these and other treatment choices available to you and the 
risks and benefits of these choices. 
 
WHAT ABOUT CONFIDENTIALITY? 
 
We will do everything we can to protect your privacy. In addition to the efforts of the study staff 
to help keep your personal information private, we have gotten a Certificate of Confidentiality 
from the US Federal Government. This certificate means that researchers cannot be forced to 
tell people who are not connected with this study, such as the court system, about your 
participation. Also, any publication of this study will not use your name or identify you 
personally. 
 
Your records may be reviewed by the US Food and Drug Administration (FDA), the ACTG, the 
US Office for Human Research Protections (OHRP), or other local, US, and international 
regulatory entities as part of their duties (insert name of site) institutional review board (IRB) (a 
committee that protects the rights and safety of participants in research), National Institutes of 
Health (NIH), study staff, study monitors, drug companies supporting this study, and their 
designees. Having a Certificate of Confidentiality does not prevent you from releasing 
information about yourself and your participation in the study. 
 
Even with the Certificate of Confidentiality, if the study staff learns of possible child abuse and/or 
neglect or a risk of harm to yourself or others, we will be required to tell the proper authorities. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 


 
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WHAT ARE THE COSTS TO ME? 
 
There will be no cost to you for the study drugs, the study visits, physical examinations, 
laboratory tests or other tests required by the study. You or your insurance company, or your 
health care system will be responsible for the costs of your regular medical care as well as for 
the costs of drugs not given by the study. 
 
WILL I RECEIVE ANY PAYMENT? 
 
You will be paid 
 at the completion of each study visit. 
 
WHAT HAPPENS IF I AM INJURED? 
 
If you are injured as a result of taking part in this study, you will be given treatment right away 
for your injuries and be referred for further treatment, if necessary. However, you or your 
insurance company may have to pay for this care. There is no program for compensation for 
such injuries, either through this institution or the NIH. You will not be giving up any of your legal 
rights by signing this consent form. 
 
WHAT ARE MY RIGHTS AS A RESEARCH PARTICIPANT? 
 
Taking part in this study is completely voluntary. You may choose not to take part in this study 
or leave this study at any time. The care that you would normally receive will not be affected if 
you decide not to take part. Your decision will not affect other studies done by NIH in which you 
may be taking part, and will not lead to any penalty or loss of benefits that you have the right to 
expect. 
 
We will tell you about new information from this or other studies that may affect your health, 
welfare, or decision to stay in this study. If you want the results of the study, let the study staff 
know. 
 
WHAT DO I DO IF I HAVE QUESTIONS OR PROBLEMS? 
 
For questions, concerns or complaints about this study or a research-related injury, contact: 
 
• 
Roger Bedimo, MS, MD, FACP 
• 
 (24 hours) 
 
This research is being overseen by an Institutional Review Board (“IRB”). An IRB is a group of 
people who perform independent review of research studies. You may talk to them at 
 if:  
 
o 
You have questions, concerns, or complaints that are not being answered by the research 
team. 
o 
You are not getting answers from the research team. 
o 
You cannot reach the research team. 
o 
You want to talk to someone else about the research. 
o 
You have questions about your rights as a research subject. 


 
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SIGNATURE PAGE ACTG Study A5360 
 
If you have read this consent form (or had it explained to you), all your questions have been 
answered and you agree to take part in this study, please sign your name below. 
 
 
 
 
 
 
Participant’s Name (print) 
 
Participant’s Signature and Date 
 
 
 
 
 
 
Study Staff Conducting 
 
Study Staff’s Signature and Date 
Consent Discussion (print)  
 
 
 
 
 
 
Witness’s Name (print) 
 
Witness’s Signature and Date 
(As appropriate) 

SAP_002.pdf: 
A5360 
Primary Statistical Analysis Plan 
 Version 2.0 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal 
Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy 
to HCV Infected Populations who are HCV Treatment Naïve with Evidence 
of Active HCV Infection: The MINMON Study 
Protocol Version 1.0 LOA #3 
ClinicalTrials.gov Identifier: NCT03512210 
< April 29, 2020 > 
Created by: 
[REDACTED]
SDAC/Harvard T.H. Chan School of Public Health 


ACTG A5360: Primary SAP V2.0 
April 29, 2020 
Page 1 of 17 
1 
VERSION HISTORY TABLE ................................................................................................ 2 
2 
INTRODUCTION .................................................................................................................. 2 
2.1 
Purpose and Scope .................................................................................................... 2 
2.2 
Summary of Major Changes ...................................................................................... 2 
3 
STUDY OVERVIEW .............................................................................................................. 3 
3.1 
Study Design .............................................................................................................. 3 
3.2 
Hypotheses ................................................................................................................. 4 
3.3 
Study Objectives ........................................................................................................ 4 
3.3.1 
Primary Objectives ............................................................................................ 4 
3.3.2 
Secondary Objectives ....................................................................................... 4 
3.3.3 
Exploratory Objectives (only the objectives addressed in the primary analysis 
are listed here) ............................................................................................ 4 
3.4 
Overview of Sample Size Considerations ................................................................. 4 
3.5 
Overview of Formal Interim Monitoring ..................................................................... 5 
4 
OUTCOME MEASURES ....................................................................................................... 6 
4.1 
Primary Outcome Measures ...................................................................................... 6 
4.1.1 
Primary Efficacy Outcome Measure .................................................................. 6 
4.1.2 
Primary Safety Outcome Measure ..................................................................... 8 
4.2 
Secondary Outcome Measures.................................................................................. 9 
4.2.1 
Secondary Outcome Measure #1 – Unplanned clinic visits ................................ 9 
4.2.2 
Secondary Outcome Measure #2 – Other AEs ................................................ 10 
4.2.3 
Secondary Outcome Measure #3 – Premature Discontinuation of HCV 
medications .............................................................................................. 11 
4.3 
Other Outcome Measures ........................................................................................ 12 
4.3.1 
Types of evaluations at unplanned clinic visits ................................................. 12 
4.3.2 
Prevalence of HCV resistance-associated substitutions (RASs) among 
participants who do not achieve SVR [if RAS data are available at time of 
analysis report] ......................................................................................... 12 
5 
STATISTICAL PRINCIPLES ............................................................................................... 13 
5.1 
General Considerations ........................................................................................... 13 
5.1.1 
Definitions ....................................................................................................... 13 
5.1.2 
Clinic Study Visit Windows .............................................................................. 13 
5.1.3 
Analysis Sets .................................................................................................. 13 
5.1.4 
Analysis Approaches ....................................................................................... 14 
6 
REPORT CONTENTS......................................................................................................... 15 
ATTACHMENT 1: WRITING TEAM ROSTER  [REDACTED].................................................... 16 
ATTACHMENT 2: TIMETABLE FOR PRIMARY ANALYSIS AND MANUSCRIPT 
PREPARATION  [REDACTED]............................................................................. 17 


ACTG A5360: Primary SAP V2.0 
April 29, 2020 
Page 2 of 17 
1 
Version History Table 
Version 
Changes Made 
Rationale 
Effective Date 
1 
Original Version (including 
protocol revisions including 
LOAs #1, #2 and #3) 
Initial version 
 5/16/2019 
2 
Edited exploratory outcomes; 
defined reference start dates; 
adjusted post MINMON visit 
windows; added HCV genotype 
to analysis approaches; updated 
report contents 
Report will focus on the 
week 24 analysis 
objectives, and therefore 
will only include 
exploratory outcomes 
related to this timeframe. 
4/29/2020 
2 
Introduction 
2.1 
Purpose and Scope 
This Primary Statistical Analysis Plan (SAP) describes the primary and secondary outcome 
measures and additional outcome measures of the A5360 study that will be included in the 
primary manuscript, and which address, at a minimum, the major primary and secondary 
objectives of the study. The Primary SAP outlines the general statistical approaches that will be 
used in the analysis of the study. It has been developed to facilitate discussion of the statistical 
analysis components among the study team, and to provide agreement between the study team 
and statisticians regarding the statistical analyses to be performed and presented in the primary 
analysis report. It also describes the results for the primary and secondary outcome measures 
that will be posted on ClinicalTrials.gov.  
Detailed outlines of tables, figures, and coding descriptions that will be included in the Primary 
Analysis Report are included in a separate document called the Primary Analysis Implementation 
Plan (AIP).  
Analyses for the Primary Analysis Report will be triggered by the study’s primary completion date 
(PCD) which is defined as the date when the Sustained Virologic Response (SVR) evaluation visit 
has occurred for all participants enrolled. The SVR evaluation visit is the first clinic visit occurring 
more than 22 weeks post study entry (and up to 76 weeks post entry), where samples for HCV 
RNA were collected).  These analyses will be finalized after all queries have been resolved.  
Analyses not included in this document (i.e. those planned for manuscripts subsequent to the 
primary one), will be outlined in a separate, Secondary Statistical Analysis Plan, and parallel 
Secondary AIP.  
2.2 
Summary of Major Changes 
Throughout this document, major updates will be in bold face type. 


ACTG A5360: Primary SAP V2.0 
April 29, 2020 
Page 3 of 17 
3 
Study Overview 
3.1 
Study Design 
Copied from Schema: 
DESIGN 
This is a phase IV open-label, multicenter, prospective study to assess 
the feasibility and efficacy of a minimal monitoring (MINMON) approach 
in active hepatitis C virus (HCV)-infected, treatment naïve participants, 
with and without HIV-1 co-infection, and with no cirrhosis or with 
compensated cirrhosis only. This study will enroll a cohort of participants 
with active HCV-infection to follow a minimal monitoring protocol, at US 
and non-US sites:  
1)
No pre-treatment HCV genotyping;
2)
Entire treatment course (84 tablets) given to participants at entry;
3)
No scheduled on-treatment laboratory monitoring or clinic visits;
4)
Remote contact with participants at week 4 (adherence counseling
and locator update) and week 22 (scheduling of SVR visit and
locator update).
5)
Participants will receive the fixed-dose combination (FDC) of
sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks.
DURATION 
72 weeks 
SAMPLE SIZE 
400 participants 
POPULATION 
Men and women aged 18 years or older with active HCV-infection of any 
genotype, HCV treatment naïve, with or without HIV-1 co-infection. 
Persons with either compensated cirrhosis or without evidence of 
cirrhosis are eligible.  
STRATIFICATION 
The study will use stratification factors to limit enrollment by certain 
subgroups. These stratification factors include geographical location 
(limited to no more than 132 participants enrolled from sites in the US 
within the overall study sample), HIV-1 infection (limited to no more than 
200 participants being HIV-1 positive within the overall study sample), 
and cirrhosis status (limited to no more than 80 participants within the 
overall study sample having compensated cirrhosis). There are no 
additional restrictions regarding participants who are both HIV-co-
infected and have compensated cirrhosis, and or/geographical 
distribution of those participants. 


ACTG A5360: Primary SAP V2.0 
April 29, 2020 
Page 4 of 17 
3.2 
Hypotheses 
A MINMON strategy to deliver interferon and ribavirin (RBV)-free pan-genotypic therapy to 
participants with active HCV infection who are HCV treatment-naïve, globally, will be efficacious 
and safe. 
3.3 
Study Objectives 
This Primary SAP addresses the following primary, secondary and selected exploratory 
objectives listed in the study protocol. Other study objectives in the protocol will be addressed in 
separate analysis plan documents.  
3.3.1 
Primary Objectives 
1.
To estimate SVR (defined as HCV RNA < lower limit of quantification [LLOQ] at least 10
weeks after the end of treatment [EOT] [which is at least 22 weeks from the study entry
visit date]).
2.
To summarize the occurrence of serious adverse events (SAEs) within 24 weeks
following study entry.
3.3.2 
Secondary Objectives 
1.
To estimate the proportion of participants with unplanned clinic visits prior to SVR
evaluation.
2.
To summarize the occurrence of adverse events, other than SAEs, within 24 weeks
following study entry.
3.
To estimate the proportion of participants who prematurely discontinue HCV treatment.
3.3.3 
Exploratory Objectives (only the objectives addressed in the primary analysis are 
listed here) 
1.
To describe the number and types of evaluations performed at unplanned visits.
2.
To estimate the prevalence of HCV resistance-associated substitutions (RASs)
among participants who do not achieve SVR [if data available].
3.4 
Overview of Sample Size Considerations 
The sample size of 400 participants in this single-arm study was chosen for statistical properties 
regarding the use of efficacy data from this study to inform the utility and feasibility of future 
studies of the MINMON approach, and the precision (based on confidence interval (CI) width) 
about sustained virologic response (SVR) efficacy outcome estimates.  A high benchmark is 
defined when the lower confidence limit of the 2-sided 95% CI about the SVR estimate is strictly 
greater than 96%.  If a high benchmark is observed in A5360, then SVR for the MINMON strategy 
exceeds 96%--and future randomized clinical trials may not be needed.  A low benchmark is 
defined as when the upper confidence limit of the 2-sided 95% CI about the SVR estimate is 


ACTG A5360: Primary SAP V2.0 
 
April 29, 2020 
Page 5 of 17 
 
strictly less than 95%.  If neither benchmark is met, then it may be desirable to use the MINMON 
approach versus SOC in future RCT considering the efficacy estimates from this study.  For 
additional details on sample size considerations, refer to protocol section 10.4. 
3.5 
Overview of Formal Interim Monitoring 
Timing and triggers for reviews: The study will undergo interim review at least annually by an 
ACTG-appointed Study Monitoring Committee (SMC). The first interim review will occur no more 
than one year after the enrollment of the first study participant or approximately 6 months after 
25% of the study sample (100 participants) have completed 12 weeks on study, whichever occurs 
earlier. An unplanned interim review will be triggered if, at any time, more than 20 persons are not 
evaluable for the SVR outcome before study discontinuation or 76 weeks following study 
enrollment. Another trigger for an unplanned interim review is if, at any time, the number of 
participants experiencing an SAE exceeds 5% of the interim analysis dataset, and the absolute 
number of participants with SAEs is at least 10.  An interim review may also be convened if a 
concern is identified by the DAIDS clinical representative, the study chairs, or study statistician in 
consultation with the team. 
Scope of reports:  Items for SMC interim review include the following: screening and accrual, 
baseline characteristics of study sample, data (and specimen) completeness, premature study 
treatment and study discontinuation, unplanned study visits, safety (serious and other adverse 
events), evaluability for primary efficacy outcome, and for interim reviews including efficacy 
outcome: SVR outcome estimation.   
Interim looks at efficacy and modification guidelines:  A planned interim review for efficacy 
will be triggered when SVR outcomes are available for approximately 100 participants, but could 
occur earlier (under case of a faster than anticipated accrual rate). The team wishes that the 
interim look at efficacy occur while the study is still accruing, so that if SVR rate is unacceptably 
low (ie, futility), that there is still an opportunity to intervene before accrual to the study is 
completed.   If the analysis sample for the initial planned review for efficacy as outlined above 
includes fewer than 40% participants from non-US clinical research sites, then a second planned 
review of efficacy will be triggered when SVR outcomes are available on approximately 230 
participants (with the upper limit of US participants of 132, this estimates at least 40% non-US 
representation in the 2nd efficacy look interim analysis sample).  The same analysis plan and 
monitoring bounds as defined in the first look as described below would be applied to this second 
look at SVR. 
Consideration would be given to closer monitoring or stopping the study if there is early and 
strong evidence to exclude the SVR rate from being 95% or higher (ie, upper confidence bound 
on a 1-sided 99.9% CI is lower than 95%). With 100 participants, this boundary would be met if 
the observed SVR rate were 86% or lower (which corresponds to 14 or more SVR non-
responders out of 100). For additional information, SVR estimates will be provided separately for 
subgroups such as defined by geographical location (i.e. by country), by HIV-coinfection status, 
and by cirrhosis status.   
However, if the SMC sees early benefit of the MINMON intervention, the team intends the study 
to proceed with full accrual and follow-up in order to confirm early evidence, and gain precision on 
the efficacy outcome estimate and other outcomes. 


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4 
Outcome Measures 
Note: Information below in italics has been formatted according to the results format 
specifications in clinicaltrials.gov.  All primary and secondary outcomes are anticipated to be 
reported with the initial results submission. 
4.1 
Primary Outcome Measures 
4.1.1 
Primary Efficacy Outcome Measure 
 
Measure Title: Percentage of Participants with Sustained Virologic Response 12 
(SVR12)   
Measure Description: SVR12  was defined as plasma HCV RNA less than the lower 
limit of quantification (LLOQ) from the earliest sample drawn at least 22 weeks following 
study treatment initiation (i.e. at a visit scheduled at least 10 weeks after scheduled end 
of study treatment).  Participants without any HCV RNA result at least 22 weeks after 
treatment initiation will be considered as having HCV RNA greater than the LLOQ. 
 A two-sided 95%, confidence interval was calculated for this percentage using the 
Wilson (score) method. 
Time Frame:  At least 22 weeks and up to 76 weeks from treatment initiation. 
Population Description:  Participants who enrolled and received first dose of study 
medication. 
Associated study objective: “To estimate SVR (defined as HCV RNA < lower limit of 
quantification [LLOQ] at least 10 weeks after the end of treatment [EOT] [which is at least 
22 weeks from the study entry visit date]).” 
Details: Due to the definition of SVR outcome measure, missing HCV RNA results will 
lower the overall percentage of participants with SVR. Therefore, various reasons for 
non-SVR (e.g., discontinued treatment early due to various reasons including 
intolerability, observed HCV RNA > LLOQ, missing evaluation for SVR (and reasons as 
known), and the number of participants meeting each reason for non-SVR, will be 
presented in order to interpret the overall SVR sample estimate. 
For interim analyses: Interim analysis is planned when SVR outcomes are available for 
approximately 100 participants. At interim reviews, SVR will be calculated only among 
those with potential to contribute to SVR (by having at least 22 weeks elapsed since 
study entry). Imputation of missing SVR evaluation as non-SVR response will only occur 
for participants for whom more than 76 weeks since study enrollment has elapsed. In 
other words, early study discontinuations prior to week 22 will not be counted in SVR 
estimation at interim review, as these could bias the estimation of SVR towards futility. 
Instead, these early study discontinuations prior to week 22 (before available for SVR 
evaluation), and others missing SVR evaluation, will contribute to the interim monitoring 


ACTG A5360: Primary SAP V2.0 
 
April 29, 2020 
Page 7 of 17 
 
trigger. For more details, refer to Overview of Formal Interim Monitoring of section 3.5 
above. 
 
 


ACTG A5360: Primary SAP V2.0 
 
April 29, 2020 
Page 8 of 17 
 
4.1.2 
Primary Safety Outcome Measure 
 
Measure Title: Percentage of Participants with an Occurrence of Serious AEs According 
to ICH Criteria 
 
Measure Description: Serious adverse events (SAEs) as defined by International 
Council for Harmonization (ICH) guidelines occurring from treatment initiation until 28 
weeks following treatment initiation (end of week 24 visit window)  
 
A two-sided, 95% confidence interval was calculated for the percentage using the Wilson 
(score) method.  
 
Time Frame: Within 28 weeks following treatment initiation. 
 
Population Description: Participants who received first dose of study medication and 
had at least one post-entry evaluation for adverse events. 
 
Associated study objective: “To summarize the occurrence of serious adverse events 
(SAEs) within 24 weeks following study entry.” 
 
Details:  All SAEs meeting this outcome measure will be summarized and described.  
Note, the timing above applies to the timing of the event occurrence, and not to when the 
event was reported. For example, an event occurring at week 23 might not be reported 
until the week 48 clinic visit.  Also, a clinic visit is not required for “evaluation for adverse 
events’’; the reporting of an AE qualifies as meeting this criterion.  This allows exclusion 
of participants who are lost after initial dose with no information on AEs following initiation 
of study treatment. 
 
 


ACTG A5360: Primary SAP V2.0 
 
April 29, 2020 
Page 9 of 17 
 
4.2 
Secondary Outcome Measures 
4.2.1 
Secondary Outcome Measure #1 – Unplanned clinic visits 
 
Measure Title: Percentage of Participants with at Least One Unplanned Clinic Visit Prior 
to SVR12 Evaluation 
Measure Description: According to the study minimal monitoring intervention, there 
were no planned clinic visits prior to study week 24, when SVR12 was scheduled to be 
evaluated.   
A two-sided, 95% confidence interval was calculated for the percentage using the Wilson 
(score) method.  
Time Frame:  From treatment initiation to week 22. 
Population Description: Participants who enrolled and received first dose of study 
medication. 
Associated study objective: “To estimate the proportion of participants with unplanned 
clinic visits prior to SVR evaluation.” 
Details: Number, reasons for and timing of unplanned clinic visits will also be 
summarized.   
 
 


ACTG A5360: Primary SAP V2.0 
 
April 29, 2020 
Page 10 of 17 
 
4.2.2 
Secondary Outcome Measure #2 – Other AEs 
 
Measure Title:  Percentage of Participants with an occurrence of one or more non-
serious, Grade >= 3 Adverse Event, or treatment limiting AE. 
Measure Description: AEs included all primary diagnoses, primary signs/symptoms, and 
primary laboratory abnormalities that either had severity grade ≥ 3 or led to a change in 
study medication. SAEs by ICH criteria were excluded as they contributed to the primary 
safety outcome measure.   
A two-sided, 95% confidence interval was calculated for the percentage using the Wilson 
(score) method.  
Time Frame: Within 28 weeks following treatment initiation. 
Population Description:  Participants who received first dose of study medication and 
had at least one post-entry evaluation for adverse events. 
Associated study objective: “To summarize the occurrence of adverse events, other 
than SAEs, within 24 weeks following study entry.” 
Details: All AEs meeting this outcome measure will be enumerated, and summarized by 
MeDdRA categorization (SOC and HLT).   
Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 
(DAIDS AE Grading Table), corrected Version 2.1, July 2017, used for severity grading. 
Note, the timing above applies to the timing of the event and not to when the event was 
reported. For example, an event occurring at week 23 might not be reported until a week 
48 clinic visit.  Also, a clinic visit is not required for “evaluation for adverse events’’; the 
reporting of an AE qualifies as meeting this criterion.  This allows exclusion of participants 
who are lost after initial dose with no information on AEs following initiation of study 
treatment. 
 
 


ACTG A5360: Primary SAP V2.0 
 
April 29, 2020 
Page 11 of 17 
 
4.2.3 
Secondary Outcome Measure #3 – Premature Discontinuation of HCV medications 
 
Measure Title: Percentage of Participants who Prematurely Discontinued HCV Study 
Medications 
Measure Description: Premature discontinuation was defined by participant self-report, 
as there were no planned clinic visits during the 12 week study medication period.  
Participants discontinuing study follow-up without information about completion of HCV 
study medications were counted as having prematurely discontinued medications. 
A two-sided, 95% confidence interval was calculated for the percentage using the Wilson 
(score) method.  
Time Frame: From treatment initiation to SVR12 evaluation.  
Population Description:  Participants who enrolled into study and received first dose of 
study medication. 
Associated study objective: “To estimate the proportion of participants who 
prematurely discontinue HCV treatment.” 
Details: Since participant reporting of the timing of stopping study treatment may be by 
participant recall more than 12 weeks after the fact, premature discontinuation will be 
defined by the final treatment dose date being fewer than 11 weeks (or fewer than 77 
days) post initial dose accounting for reported treatment interruptions. The timing and 
reasons for premature discontinuation will be summarized, as those details are available 
in the study database.  As available, any other details on the disposition of study 
treatment (e.g. treatment interruptions), will be summarized. 
 
 


ACTG A5360: Primary SAP V2.0 
 
April 29, 2020 
Page 12 of 17 
 
4.3 
Other Outcome Measures  
4.3.1 
Types of evaluations at unplanned clinic visits 
This will be a descriptive analysis to summarize the nature of evaluations at unplanned 
clinic visits, e.g. whether and number of lab tests. 
4.3.2 
Prevalence of HCV resistance-associated substitutions (RASs) among participants 
who do not achieve SVR [if RAS data are available at time of analysis report] 
Measure Title: Percentage of Participants with HCV resistance-associated substitutions 
(RASs) among non-SVR Participants  
Measure Description: HCV resistance-associated substitutions (RASs) were defined as 
amino acid substitution that confer reduced susceptibility to a direct-acting antiviral (DAA) 
and may contribute to virology failure. Non-SVR responders were assessed for RASs by 
comparing SVR12 sequence data with baseline to assess amino acid changes in the 
NS5A and NS5B gene regions. 
Time Frame: At time of SVR12 evaluation.  
Population Description:  Participants who do not achieve SVR. 
Associated study objective: “To estimate the prevalence of HCV resistance-associated 
substitutions (RASs) among participants who do not achieve SVR.” 
Details: Those who do not achieve SVR with an observed HCV RNA >LLOQ will have 
both baseline and SVR specimens tested for HCV RASs by sequencing the NS5A and 
NS5B regions. Participants in this sub-set with HCV RASs present in their SVR specimen 
that were not present in their baseline specimen will be enumerated along with the 
relative frequencies of new RASs. A description of the observed RASs will also be 
provided.  
Note: This outcome will only be included in the analysis report if data on RASs is 
available to the statistician and ready for analysis. 
 
 
 
 
 
 
 


ACTG A5360: Primary SAP V2.0 
April 29, 2020 
Page 13 of 17 
5 
Statistical Principles 
5.1 
General Considerations 
5.1.1 
Definitions 
Baseline: Any characteristic measured or evaluated prior to the first dose of study medication 
(including information collected at screening) can be used as a ‘baseline’ characteristic. Areas 
where use of screening could induce bias (due to eligibility criteria) will be noted in any analysis, 
as applicable. 
SVR:  Target not detected (TND) result is a valid that also qualifies as <LLOQ and will be 
counted as an SVR responder. When handling of multiple HCV RNA results, the valid result from 
the earliest sample drawn within the SVR evaluation window (starting 22 weeks post study 
treatment initiation) will be used for analysis.  
Reference Start Dates: 

Study enrollment date: Date participant was enrolled on study.

Treatment start date: Date participant took first dose of study treatment.
5.1.2 
Clinic Study Visit Windows 
MINMON intervention EPOCH [Step 1]: The first follow-up clinic visit at study week 24, for 
primary outcome SVR evaluation has a window of -14 days to +28 days. If week 24 study visit is 
missed, this “primary SVR evaluation” visit can occur anytime up to study week 72 which is the 
end of study follow-up. 
Post SVR, post MINMON, or follow-up EPOCH [Step 2]: Two clinic visits are scheduled post SVR 
at week 48 and 72. The ranges of week 48 clinic visits were examined and the observed range is 
used for visit window; weeks 48 has a window of -28/+60 days. Week 72 has a window of ± 28 
days.   
5.1.3 
Analysis Sets 
Enrolled participants who do not start study medication will be excluded from all analyses. Note 
that per protocol instructions, the first dose of study medication is to be observed in the study 
clinic during the entry evaluation visit. 
Full analysis sample (= Efficacy analysis sample at final analysis): Participants who started 
study medication.  For the efficacy analysis sample for interim reviews, refer to section:  4.1.1 
Primary Efficacy Outcome Measure. At interim analyses, the efficacy analysis sample will differ 
from the full analysis sample as follows: participants missing HCV RNAs for SVR evaluation will 
not be counted as SVR non-responders unless they enrolled more than 76 weeks prior to dataset 
finalization. Thus, the efficacy analysis sample at interim reviews will be based on observed HCV 
RNAs in the SVR evaluation window plus participants who both left the study without a result for 
SVR evaluation and who enrolled more than 76 weeks ago (and thus can no longer be evaluated 
for SVR on study). 


ACTG A5360: Primary SAP V2.0 
April 29, 2020 
Page 14 of 17 
Safety analysis sample: Participants who started study medication and who were evaluated for 
AEs for the time period after first dose of study treatment through up to 24 week later. This 
criterion will be met for any participant having an unscheduled visit prior to week24/SVR 
evaluation, or any participant having a week 24 or SVR evaluation visit. At interim analysis, due to 
no planned study clinic visits prior to study week 24, this analysis sample include all participants 
who started treatment, and only exclude those who were both known lost to all follow-up and 
without any follow-up for AEs. This sample will be split into subgroups defined by those having 
week 24/SVR evaluation visit versus not. 
5.1.4 
Analysis Approaches 
The analysis of each objective addressed in this SAP will be conducted using the appropriate 
analysis sample as defined in section 4.1. 
As this is a single arm study, the primary descriptive and statistical inference on outcomes will be 
performed on the entire specified analysis sample as a single group, and focus on estimation.  
However, as there exist key subgroups upon which separate estimates for outcomes is desired,  
analyses will often (as specified below) be repeated within subgroups defined by the following: 
o
Country (to help inform each MOH or other, policy groups, as well as serving as an
imperfect surrogate for HCV genotype)
o
Cirrhosis status (compensated cirrhotic and  non-cirrhotic by classification by FIB-4
score)
o
HIV-1 infection status (positive and  negative)
o
Sex assigned at birth (female and male)
o
If data are available, by HCV genotype
However, there are no plans to perform formal hypothesis testing for differences in outcomes 
among subgroups. 
All statistical hypothesis testing at final analysis, will use the nominal significance level of 0.05. 
See detailed specifications at interim reviews for alternative significance levels. 


ACTG A5360: Primary SAP V2.0 
April 29, 2020 
Page 15 of 17 
6 
Report Contents 
Detailed descriptions of the content of each of the following sections are given in the AIP: 
1.
CONSORT Diagram (final analysis only)
2.
Accrual
3.
Baseline characteristics
4.
Study conduct
a.
Study status and follow-up
b.
Study medication disposition
c.
Remote contact at week 4
d.
Adherence of medication, premature discontinuation of study treatment
e.
Remote contact at week 22
f.
Data and specimen availability (other than for SVR evaluation)
g.
Unplanned Clinic Visits (number/reasons)
5.
Safety
a.
Primary Safety Outcome Measure: SAEs within 24 weeks
b.
Secondary Safety Outcome Measure: other AEs within 24 weeks
c.
Summary of other AEs (all AEs after 24 weeks)
d.
Summary of pregnancies that occur during study participation
e.
Summary of HIV-1 RNA among PLWH at Week 24/SVR visit
6.
Efficacy
a.
Study visit of SVR collection
b.
SVR12 estimation
i.
Summary of details (e.g assay, LLOQ, lab) used to evaluate SVR
ii.
Estimation within subgroups
iii.
Reasons for non-SVR
iv.
Summary of participants not achieving SVR (baseline characteristics,
study/treatment disposition, safety and tolerability information)
c.
Summary of HCV RASs among participant not achieving SVR [if data available]

Prot_001.pdf: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of 
a Minimal Monitoring Strategy to Deliver Pan-genotypic 
Ribavirin-free HCV Therapy to HCV Infected Populations who 
are HCV Treatment Naïve with Evidence of Active HCV 
Infection: The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
This file contains the current ACTG A5360 protocol, which includes 
the following document:  
Letter of Amendment #5, dated 28 July 2020
Letter of Amendment #4, dated 22 June 2020
Clarification Memorandum #3, dated 09 April 2020
Clarification Memorandum #2, dated 23 September 2019
Clarification Memorandum #1, dated 26 March 2019
Letter of Amendment #3, dated 11 February 2019
Letter of Amendment #2, dated 08 August 2018
Letter of Amendment #1, dated 15 June 2018
Protocol Version 1.0, dated 10 January 2018


Letter of Amendment #5 
          Page  1 of 4 
28 Jul 2020 
ACTG A5360 Protocol Version 1.0 
Letter of Amendment #5 for: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: 
The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
Letter of Amendment Date: 28 July 2020 
ACTG NETWORK COORDINATING CENTER 
Social & Scientific Systems, a DLH Company 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD  20910-3714 
Phone: 301-628-3000 
Fax: 301-628-3302 
________________________________________ 
LETTER OF AMENDMENT #5 
DATE:      July 28, 2020 
TO: 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
FROM:      
A5360 Protocol Team 
SUBJECT: 
Letter of Amendment #5 for Protocol A5360 
The following information affects the A5360 study and must be forwarded to each site’s 
institutional review board (IRB)/ethics committee (EC) as soon as possible for their 
information and review. This Letter of Amendment (LOA) must be approved by the IRB/EC 
before implementation.  
The following information may also affect the Sample Informed Consent. The IRB/EC is 
responsible for determining the process of informing participants of the contents of this LOA. 
Upon receiving final IRB/EC and any other applicable regulatory entity approvals for this 
LOA, sites should implement the LOA immediately. Sites are still required to submit an LOA 
registration packet to the DAIDS Protocol Registration Office (PRO) at the Regulatory Support 
Center. Sites will receive a registration notification for the LOA once the DAIDS PRO verifies 


Letter of Amendment #5 
          Page  2 of 4 
28 Jul 2020 
ACTG A5360 Protocol Version 1.0 
that all required LOA registration documents have been received and are complete. An LOA 
registration notification from the DAIDS PRO is not required prior to implementing the LOA. A 
copy of the LOA registration notification, along with this letter and any IRB/EC 
correspondence, should be retained in the site’s regulatory file. 
The main reason for this LOA is to provide additional guidance for the resumption of study visits for 
non-US sites, in the midst of the ongoing COVID-19 pandemic and in follow-up to the COVID-19-
related LOA #4, dated 06/22/20. 
This LOA is being implemented for the following reason: 

Given the evolving pandemic in non-US settings, a team decision has been made to extend the
upper window for the week 72 in-person visit for non-US sites to February 28, 2021, which is the 
last date for which this visit can be completed. If non-US sites are unable to complete the week 
72 in-person visit by this date, this will be considered a missed visit. In response, the following 
sections have been updated: Table 6.1-2, section 6.2.4, and section 6.2.5. 
The following are changes (noted in bold or strikethrough) to A5360, Version 1.0, dated 01/10/18, 
titled “A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy to 
Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations who are HCV 
Treatment Naïve with Evidence of Active HCV Infection: The MINMON Study.” These changes will 
be included in the next version of the A5360 protocol if it is amended at a future date. Changes that 
have already been made (either by LOA or by CM) have been incorporated in the excerpted text 
shown below (and are no longer presented in bold or strikethrough).  
1.
Table 6.1-2 (Schedule of Evaluations: Step 2 Visits Post SVR Evaluation), the visit windows for
weeks 48 and 72 have been updated as shown in the excerpt from the table below.
Evaluation 
Weeks 
42 
48 
68 
72
Window ±28 days, except for the following: 
In-person week 48 for non-US participants ONLY: Window is -28/ +56
days
In-person week 72 for US participants ONLY: Window is -28 days through
October 31, 2020 (see Notes A, B, and C).
In-person week 72 for non-US participants ONLY: Window is -28 days
through February 28, 2021 (see Notes D and E).
NOTE A: The extension in the week 72 visit for US participants applies only to study participants with 
completed week 24/SVR visit by the date of the A5360 Version 1.0 Clarification Memo #3, dated 
04/09/20. 
NOTE B: The extension in the week 72 visit also covers US participants who time out of the week 72 
window (implemented via CM #3, dated 04/09/20), before the approval of A5360 Version 1.0 LOA 
#4, dated 06/22/20. 
NOTE C: If the week 72 in-person visit for US participants cannot be completed by October 31, 
2020, this will be considered a missed visit.  
NOTE D: The extension in the week 72 visit also covers non-US participants who time out of 
the week 72 window before the approval of A5360 Version 1.0 LOA #5, dated 07/28/20. 
NOTE E: If the week 72 in-person visit for non-US participants cannot be completed by 
February 28, 2021, this will be considered a missed visit. 


Letter of Amendment #5 
          Page 3 of 4 
28 Jul 2020 
ACTG A5360 Protocol Version 1.0 
2.
Section 6.2.4, Post-Entry Evaluations, the following subsection has been added:
Alternate Completion of Post-Entry Evaluations

Post-SVR week 48 visit:
1) For non-US participants: The post-SVR week 48 in-person visit may be scheduled to
occur up to and including 56 days after the week 48 ideal visit date. Complete the week
48 visit per Table 6.1-2 (Schedule of Evaluations: Step 2 - Visits Post SVR Evaluation).
2) For all participants: If a week 48 in-person visit cannot be completed before the visit
window closes, enter the visit as, “Participant unable to come to clinic due to COVID-19,”
using the instructions provided by the Data Management Center (DMC), entitled,
“COVID-19 DMC Updates-FINAL.”

Post-SVR week 72 visit:
1) For US participants: The post-SVR week 72 in-person visit may be scheduled through
October 31, 2020. Complete the week 72 visit per Table 6.1-2 (Schedule of Evaluations:
Step 2 - Visits Post SVR Evaluation).
NOTE: If a week 72 in-person visit cannot be completed for a US participant by October
31, 2020, this will be considered a missed visit.
2) For non-US participants: If a week 72 in-person visit cannot be completed before the visit
window closes, contact the A5360 core team (actg.coreA5360@fstrf.org) for further
guidance. The post-SVR week 72 in-person visit may be scheduled through 
February 28, 2021. Complete the week 72 visit per Table 6.1-2 (Schedule of 
Evaluations: Step 2 - Visits Post SVR Evaluation). 
NOTE: If a week 72 in-person visit cannot be completed for a non-US participant by 
February 28, 2021, this will be considered a missed visit. 
3.
Section 6.2.5, Study Completion Evaluations, the first paragraph has been updated as follows:
For Step 2, week 72 in-person visit (± -28 days, through February 28, 2021 for non-US
participants; -28 days, through October 31, 2020, for US participants) will be the final study visit
for all participants, independent of the entry week for Step 2.
4.
Protocol Signature Page
A Protocol Signature Page (PSP) is appended for submission to the DAIDS Protocol Registration
System (DPRS) as part of the LOA registration packet.


Letter of Amendment #5 
          Page 4 of 4 
28 Jul 2020 
ACTG A5360 Protocol Version 1.0 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy to 
Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations who are HCV 
Treatment Naïve with Evidence of Active HCV Infection: The MINMON Study 
SIGNATURE PAGE 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations (45 CFR 46); applicable US Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
Principal Investigator: _____________________________________________________ 
Print/Type 
Signed: _______________________________________________Date: _____________ 
Name/Title 


Letter of Amendment #4 
          Page 1 of 4 
22 Jun 2020 
ACTG A5360 Protocol Version 1.0 
Letter of Amendment #4 for: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: 
The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
Letter of Amendment Date: 22 June 2020 
ACTG NETWORK COORDINATING CENTER 
Social & Scientific Systems   
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD 20910-3714 
Phone: 301-628-3000 
Fax: 301-628-3302 
LETTER OF AMENDMENT #4 
DATE: 
June 22, 2020 
TO: 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
FROM: 
A5360 Protocol Team 
SUBJECT: 
Letter of Amendment #4 for Protocol A5360 
The following information affects the A5360 study and must be forwarded to each site’s 
institutional review board (IRB)/ethics committee (EC) as soon as possible for their 
information and review. This Letter of Amendment (LOA) must be approved by the 
IRB/EC before implementation. 
The following information may also affect the Sample Informed Consent. The IRB/EC is 
responsible for determining the process of informing participants of the contents of this 
LOA. 
Upon receiving final IRB/EC and any other applicable regulatory entity approvals for this 
LOA, sites should implement the LOA immediately. Sites are still required to submit an 
LOA registration packet to the DAIDS Protocol Registration Office (PRO) at the 
Regulatory Support Center. Sites will receive a registration notification for the LOA once 
the DAIDS PRO verifies that all required LOA registration documents have been received 


Letter of Amendment #4 
          Page 2 of 4 
22 Jun 2020 
ACTG A5360 Protocol Version 1.0 
and are complete. An LOA registration notification from the DAIDS PRO is not required 
prior to implementing the LOA. A copy of the LOA registration notification, along with 
this letter and any IRB/EC correspondence, should be retained in the site’s regulatory 
file. 
The main reason for this LOA is to provide guidance for the resumption of study visits in follow- 
up to the COVID-19-related Clarification Memo #3 (CM #3), dated 04/09/20, as US and Non- 
US sites begin to open to research visits. This LOA is formal notification that the temporary 
pause of all study visits as stated in CM #3 is now lifted. All sites should contact study 
participants when sites are able to resume in-person research visits to schedule the participant’s 
next visit. This contact can be considered the remote contact corresponding to week 42 or week 
68 and must be documented in the participant’s study file. 
This LOA is being implemented for the following reasons: 

A team decision has been made to extend the upper window for the week 72 in-person visit
for US sites, to October 31, 2020, which is the last date for which this visit can be 
completed. If US sites are unable to complete the week 72 in-person visit by this date, this 
will be considered a missed visit. In response, the following sections have been updated: 
Table 6.1-2, section 6.2.4, and section 6.2.5. 

Per DAIDS directive, COVID-19-related changes made via CM #3 have been incorporated.
In response, the following sections have been updated: Table 6.1-2, section 6.2.4, and
section 6.2.5.
The following are changes (noted in bold or strikethrough) to A5360, Version 1.0, dated 
01/10/18, titled “A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal 
Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The MINMON 
Study.” These changes will be included in the next version of the A5360 protocol if it is amended 
at a future date. Changes that have already been made (either by LOA or by CM) have been 
incorporated in the excerpted text shown below (and are no longer presented in bold or 
strikethrough). 
1.
Table 6.1-2 (Schedule of Evaluations: Step 2- Visits Post SVR Evaluation), the visit windows
for weeks 48 and 72 have been updated as shown in the excerpt from the table below.
Evaluation 
Weeks
42 
48 
68 
72 
Window ±28 days, except for the following: 
In-person week 48 for non-US participants ONLY: Window is -28/
+56 days

In-person week 72 for US participants ONLY: Window is -28,
/+84 days through October 31, 2020 (see Notes A, B, and C).
NOTE A: The extension in the week 72 visit for US participants applies only to study 
participants with completed week 24/SVR visit by the date of the A5360 Version 1.0 
Clarification Memo #3, dated 04/09/20. 
NOTE B: The extension in the week 72 visit also covers participants who time out of the 
week 72 window (implemented via CM #3, dated 04/09/20), before the approval of A5360 


Letter of Amendment #4 
          Page 3 of 4 
22 Jun 2020 
ACTG A5360 Protocol Version 1.0 
Version 1.0 LOA #4, dated 06/22/20. 
NOTE C: If the week 72 in-person visit for US participants cannot be completed by 
October 31, 2020, this will be considered a missed visit. 
2.
Section 6.2.4, Post-Entry Evaluations, the following sentence has been added at the end of
the first paragraph in the Step 2 Registration subsection:
Refer to the Alternate Completion of Post-Entry Evaluations subsection for the
instructions on completing study visits when an in-person visit cannot be safely
conducted.
3.
Section 6.2.4, Post-Entry Evaluations, the following subsection has been added:
Alternate Completion of Post-Entry Evaluations

Post-SVR week 48 visit:
1) For non-US participants: The post-SVR week 48 in-person visit may be
scheduled to occur up to and including 56 days after the week 48 ideal visit
date. Complete the week 48 visit per Table 6.1-2 (Schedule of Evaluations:
Step 2 - Visits Post SVR Evaluation).
2) For all participants: If a week 48 in-person visit cannot be completed before the
visit window closes, enter the visit as, “Participant unable to come to clinic
due to COVID-19,” using the instructions provided by the Data Management
Center (DMC), entitled, “COVID-19 DMC Updates-FINAL.”

Post-SVR week 72 visit:
1) For US participants: The post-SVR week 72 in-person visit may be scheduled
through October 31, 2020 84 days after the week 72 ideal visit date. Complete
the week 72 visit per Table 6.1-2 (Schedule of Evaluations: Step 2 - Visits Post
SVR Evaluation).
NOTE: If a week 72 in-person visit cannot be completed for a US participant by
October 31, 2020, this will be considered a missed visit.
2) For non-US participants: If a week 72 in-person visit cannot be completed
before the visit window closes, contact the A5360 core team
(actg.coreA5360@fstrf.org) for further guidance.
4.
Section 6.2.5, Study Completion Evaluations, the first paragraph has been updated as
follows:
For Step 2, week 72 in-person visit (±28 days for non-US participants, -28/+84 days,
through October 31, 2020, for US participants) will be the final study visit for all
participants, independent of the entry week for Step 2.
5.
Protocol Signature Page
A Protocol Signature Page (PSP) is appended for submission to the DAIDS Protocol
Registration System (DPRS) as part of the LOA registration packet.


Letter of Amendment #4 
          Page 4 of 4 
22 Jun 2020 
ACTG A5360 Protocol Version 1.0 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy to 
Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations who are HCV 
Treatment Naïve with Evidence of Active HCV Infection: The MINMON Study 
SIGNATURE PAGE 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States 
(US) Health and Human Service regulations (45 CFR 46); applicable US Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
Principal Investigator: 
Print/Type 
Signed: 
Date:  
     Name/Title 


Clarification Memo #3 
          Page 1 of 3 
09 Apr 2020 
ACTG A5360 Protocol Version 1.0 
Clarification Memo #3 for: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: 
The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
Clarification Memo Date: 09 April 2020 
ACTG NETWORK COORDINATING CENTER 
Social & Scientific Systems  
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD 20910-3714  
Phone: 301-628-3000 
Fax: 301-628-3302 
CLARIFICATION MEMO 
DATE: 
April 9, 2020 
TO: 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
FROM: 
A5360 Protocol Team 
SUBJECT: 
Clarification Memo #3 for Protocol A5360 (COVID-19) 
This clarification memo (CM) does not result in a change in the protocol informed 
consent document. The Division of AIDS (DAIDS) has determined that these protocol 
changes and clarifications should be implemented immediately in response to the 
COVID-19 pandemic, which poses a safety risk to participants and site staff. Sites do not 
need institutional review board (IRB) approval prior to implementing this CM. 
DAIDS does not require sites to forward this CM to their IRB; however, sites must follow 
their IRB's policies and procedures. If IRB review of CMs is required at a site, that site 
must submit this document for review. 
Each site should file a copy of this CM with the protocol for reference. 


Clarification Memo #3 
          Page 2 of 3 
09 Apr 2020 
ACTG A5360 Protocol Version 1.0 
The main reason for this CM is to provide guidance for study visits during the COVID-19 
pandemic. The instructions in this CM supersede the instructions that were in the memo 
released by the A5360 Protocol Team on 03/23/20 with subject “COVID-19: Temporary Pause 
for Protocol A5360 (MINMON Study) and Guidance for Enrolled Participants.” 
All sites should contact study participants to inform them of the temporary pause in all study 
visits and that they will be contacted to schedule their next visit when the pause is lifted. This 
contact must be documented in the participant’s study file but does NOT need to be recorded on 
the eCRFs and reported to the A5360 core team. 
When the temporary pause on study visits is lifted, sites should contact study participants to 
schedule their next visit. This contact can be considered the remote contact corresponding to 
week 42 or week 68. This contact must be documented in the participant’s study file. 
The A5360 Protocol Team is closely monitoring the situation concerning the COVID-19 
pandemic. New guidance will be released in the beginning of May 2020, if needed. 
The following are clarifications (noted in bold or strikethrough) to Protocol A5360, Version 1.0, 
01/10/18, titled “A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal 
Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The 
MINMON Study.” These clarifications will be included in the next version of the A5360 protocol if 
it is amended at a future date. 
1.
In section 6.1, Table 6.1-2 (Schedule of Evaluations: Step 2- Visits Post SVR Evaluation),
the visit windows for weeks 48 and 72 have been updated as shown in the excerpt from the
table below.
Evaluation 
Weeks
42 
48 
68 
72 
Window ±28 days, except for the following: 
Week 48 for non-US participants ONLY: window is -28/+56 days
Week 72 for US participants ONLY: window is -28/+84 days (see
note)
NOTE: The extension in the week 72 visit for US participants applies only to study 
participants with completed week 24/SVR visit by the date of the A5360 Version 1.0 
Clarification Memo #3, dated 04/09/20. 
2.
In section 6.2.4, Post-Entry Evaluations, the following sentence has been added at the end
of the first paragraph in the Step 2 Registration subsection:
Refer to the Alternate Completion of Post-Entry Evaluations subsection for the
instructions on completing study visits when an in-person visit cannot be safely
conducted.
3.
In section 6.2.4, Post-Entry Evaluations, the following subsection has been added:
Alternate Completion of Post-Entry Evaluations

Post-SVR week 48 visit:


Clarification Memo #3 
          Page 3 of 3 
09 Apr 2020 
ACTG A5360 Protocol Version 1.0 
1) For non-US participants: The post-SVR week 48 visit may be scheduled to
occur up to and including 56 days after the week 48 ideal visit date.
Complete the week 48 visit per Table 6.1-2 (Schedule of Evaluations: Step 2
- Visits Post SVR Evaluation).
2) For all participants: If a week 48 visit cannot be completed before the visit
window closes, enter the visit as a “Participant unable to come to clinic
due to COVID-19” using the instructions provided by the Data Management
Center (DMC), entitled “COVID-19 DMC Updates-FINAL.”

Post-SVR week 72 visit:
1) For US participants: The post-SVR week 72 visit may be scheduled to occur
up to and including 84 days after the week 72 ideal visit date. Complete the
week 72 visit per Table 6.1-2 (Schedule of Evaluations: Step 2 - Visits Post
SVR Evaluation).
2) For all participants: If a week 72 visit cannot be completed before the visit
window closes, contact the A5360 core team (actg.coreA5360@fstrf.org) for
further guidance.
4.
In section 6.2.5, Study Completion Evaluations, the first paragraph has been updated as
follows:
For Step 2, week 72 (±28-days for non-US participants, -28/+84 days for US 
participants) will be the final study visit for all participants, independent of the entry week 
for Step 2. 


Clarification Memo #2 
          Page 1 of 5 
23 Sep 2019 
ACTG A5360 Protocol Version 1.0 
Clarification Memo #2 for: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: 
The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
Clarification Memo Date: 23 September 2019 
ACTG NETWORK COORDINATING CENTER 
Social & Scientific Systems 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD  20910-3714 
Phone: 301-628-3000 
Fax: 301-628-3302 
CLARIFICATION MEMO 
DATE:  
September 23, 2019 
TO: 
 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
FROM: 
A5360 Protocol Team  
SUBJECT: 
Clarification Memo #2 for Protocol A5360 
This clarification memo (CM) does not result in a change in the protocol informed consent 
document. The Division of AIDS does not require you to forward it to your institutional 
review board (IRB); however, you must follow your IRB's policies and procedures. If IRB 
review of clarification memos is required at your site, please submit this document for 
review. 
Each site should file a copy of this CM with the protocol for reference. 
The protocol clarifications contained in this memo should be implemented immediately. 
The following are clarifications (noted in bold or strikethrough) to Protocol A5360, Version 1.0, 
01/10/18, titled "A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal 


Clarification Memo #2 
          Page 2 of 5 
23 Sep 2019 
ACTG A5360 Protocol Version 1.0 
Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The MINMON 
Study.” Changes that have already been made since the previous version (either by letter of 
amendment or clarification memo) have been incorporated in the excerpted text shown below (and 
are no longer presented in bold). These clarifications will be included in the next version of the 
A5360 protocol if it is amended at a future date. 
1.
Section 4.1.7 (Inclusion Criteria [Step 1]): The laboratory requirement for non-US laboratories
has been revised to read:
For HIV co-infected participants, HIV-1 RNA obtained within 90 days prior to study entry by
any US laboratory that has a CLIA certification or its equivalent, or at any network-approved
non-US laboratory that is VQA certified operates in accordance with Good Clinical Laboratory
Practices (GCLP) and participates in appropriate external quality assurance programs.
2.
Section 4.1.8 (Inclusion Criteria [Step 1]): The laboratory requirement for non-US laboratories
has been revised to read:
For HIV co-infected participants, CD4+ cell count obtained within 90 days prior to study entry
at any US laboratory that has a CLIA certification or its equivalent, or at any network-approved
non-US laboratory that is Immunology Quality Assessment (IQA) certified. operates in
accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate
external quality assurance programs. 
3.
Section 6.1-1 (Schedule of Evaluations: Step 1- Visits up Until SVR Evaluation): Step 2
Registration has been added to the SOE to match section 6.2.3 (Step 2 Registration
Evaluations) and to clarify that registration for Step 2 must occur on the same day of the last
visit on Step 1.
Section 6.1-1 (Schedule of Evaluations: Step 1- Visits up Until SVR Evaluation) 
Evaluation 
Screening 
Entry/Week 
0 
Weeks 
SVR 
Evaluation 
Visit (if week 
24 visit is 
missed; can 
occur up to 
week 72) 
Unplanned 
Study Visits 
(see section 
6.2.6) 
4 
22 
24 
Window +7 days 
Window -
14/+28 days 
Documentation of 
Active HCV Infection 
X 
Documentation of 
HIV-1 Status 
X 
Calculated FIB-4 
Score 
X 
X 
X 
As needed. 
MELD Score 
X 
Documentation of 
Cirrhosis Status 
X 
X 
X 
As needed. 
Calculated CTP 
Score  (if cirrhotic by 
FIB-4) 
X 
X 
X 


Clarification Memo #2 
          Page 3 of 5 
23 Sep 2019 
ACTG A5360 Protocol Version 1.0 
Evaluation 
Screening 
Entry/Week 
0 
Weeks 
SVR 
Evaluation 
Visit (if week 
24 visit is 
missed; can 
occur up to 
week 72) 
Unplanned 
Study Visits 
(see section 
6.2.6) 
4 
22 
24 
Window +7 days 
Window -
14/+28 days 
Liver Elastography 
(see section 6.3.7) 
X
X
X
Medical History 
X 
X 
Medication History 
X 
X 
Clinical Assessments  
X 
X 
X 
X 
As needed. 
Hematology 
X 
X 
X 
X 
Liver Function Tests 
X 
X 
X 
X 
Blood Chemistries 
X 
X 
X 
X 
As needed. 
Calculated Creatinine 
Clearance 
X 
INR 
X 
X 
X 
As needed. 
Pregnancy Testing 
X 
X 
If pregnancy is suspected. 
HBV Panel 
X 
CD4+ (if HIV+) 
X 
X 
X 
Plasma HIV-1 RNA (if 
HIV+) 
X 
X 
X 
Plasma HCV RNA 
X 
X 
X 
Stored 
Plasma/PBMC/Serum 
X
X
X 
As needed. 
(Plasma 
sample will 
be stored if 
blood 
sample 
obtained.) 
Adherence 
Assessment 
X (via 
remote 
contact) 
X
X
Health Outcomes 
Questionnaire 
X
X
X
X 
Health Care 
Utilization 
Questionnaire 
X
X
X
X 
Substance Use 
Questionnaire 
X
X
X
HCV Therapy 
Dispensed/First Dose 
Observed 
X


Clarification Memo #2 
          Page 4 of 5 
23 Sep 2019 
ACTG A5360 Protocol Version 1.0 
Evaluation 
Screening 
Entry/Week 
0 
Weeks 
SVR 
Evaluation 
Visit (if week 
24 visit is 
missed; can 
occur up to 
week 72) 
Unplanned 
Study Visits 
(see section 
6.2.6) 
4 
22 
24 
Window +7 days 
Window -
14/+28 days 
Adherence Education 
and Counseling 
X
Pregnancy 
Prevention 
Counseling 
X 
X 
Cirrhosis Counseling 
X 
X 
X 
HCV Risk-reduction 
Counseling 
X
X
X
Step 2 Registration 
X (Registration for Step 2 
must occur on the same 
day of the last visit on 
Step 1; see section 6.2.3)
Locator Information 
X 
Update 
information, if 
needed. 
Remote Contact with 
Participants Outside 
of Planned Clinic 
Visits  
X 
X (see 
note in 
section 
6.2.4) 
4.
Section 6.3 (Instructions for Evaluations): The following paragraph has been added as the first
paragraph of this section, and the link to the Source Document Guidelines on the DAIDS
website has been updated in the now second paragraph.
Each study site and laboratory involved in this study will comply with the DAIDS policy
on Requirements for DAIDS Funded and/or Sponsored Laboratories in Clinical Trials
Policy, which is available at
https://www.niaid.nih.gov/sites/default/files/laboratorypolicy1.pdf.
All clinical and laboratory information required by this protocol is to be present in the source
documents. Sites must refer to the Source Document Guidelines on the DAIDS website for
information about what must be included in the source document:
https://www.niaid.nih.gov/sites/default/files/documents/sourcedocappndx.pdf.
https://www.niaid.nih.gov/sites/default/files/daids-sourcedocpolicy.pdf.
5.
Section 6.3.12 (Immunologic Studies [For HIV co-infected participants]): The laboratory
requirements have been revised to read:
CD4+
Screening Obtain absolute CD4+ count must be performed within 90 days prior to study entry
from at a laboratory that possesses a CLIA certification or equivalent (US sites), or IQA
certification (non-US sites).


Clarification Memo #2 
          Page 5 of 5 
23 Sep 2019 
ACTG A5360 Protocol Version 1.0 
For entry and post-entry evaluations, all laboratories must possess a CLIA certification or 
equivalent (US sites), or and must be certified for protocol testing by the DAIDS Immunology 
Quality Assurance (IQA) Program certification (non-US sites). 
6.
Section 6.3.13 (Virologic Studies [Plasma HIV-1 RNA (For HIV Co-infected Participants]): The
laboratory requirements have been revised to read:
Plasma HIV-1 RNA (For HIV Co-infected Participants)
Screening HIV-1 RNA must be performed within 90 days prior to study entry by at a laboratory
that possesses a CLIA certification or equivalent (US sites) or Virology Quality Assurance
(VQA) certification (non-US sites).


Clarification Memo #1 
          Page 1 of 2 
26 Mar 2019 
ACTG A5360 Protocol Version 1.0 
Clarification Memo #1 for: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: 
The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
Clarification Memo Date: 26 March 2019 
ACTG NETWORK COORDINATING CENTER 
Social & Scientific Systems 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD  20910-3714 
Phone: 301-628-3000 
Fax: 301-628-3302 
CLARIFICATION MEMO 
DATE:  
March 26, 2019 
TO: 
 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
FROM: 
A5360 Protocol Team  
SUBJECT: 
Clarification Memo #1 for Protocol A5360 
This clarification memo (CM) does not result in a change in the protocol informed consent 
document. The Division of AIDS does not require you to forward it to your institutional 
review board (IRB); however, you must follow your IRB's policies and procedures. If IRB 
review of clarification memos is required at your site, please submit this document for 
review. 
Each site should file a copy of this CM with the protocol for reference. 
The protocol clarifications contained in this memo should be implemented immediately. 
The following are clarifications (noted in bold or strikethrough) to Protocol A5360, Version 1.0, 
01/10/18, titled "A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal 


Clarification Memo #1 
          Page 2 of 2 
26 Mar 2019 
ACTG A5360 Protocol Version 1.0 
Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The MINMON 
Study.” These clarifications will be included in the next version of the A5360 protocol if it is 
amended at a future date. 
1.
Section 4.1.10 (Inclusion Criteria): The measurement unit for albumin values has been revised
to read:

Albumin >3.0 g/dL
2.
Section 4.1.10 (Inclusion Criteria): The measurement unit for platelet count values has been
revised to coincide with the platelet count measurement unit found in section 6.3.3 (Calculated
FIBROSIS-4 [FIB-4] Score):

Platelet count >50,000/mm3 x 109/L


Letter of Amendment #3 
          Page 1 of 3 
11 Feb 2019 
ACTG A5360 Protocol Version 1.0 
Letter of Amendment #3 for: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: 
The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
Letter of Amendment Date: 11 February 2019 


Letter of Amendment #3 
          Page 2 of 3 
11 Feb 2019 
ACTG A5360 Protocol Version 1.0 


Letter of Amendment #3 
          Page 3 of 3 
11 Feb 2019 
ACTG A5360 Protocol Version 1.0 


Letter of Amendment #2 
          Page 1 of 5 
08 Aug 2018 
ACTG A5360 Protocol Version 1.0 
Letter of Amendment #2 for: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal 
Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV 
Infected Populations who are HCV Treatment Naïve with Evidence of Active HCV 
Infection: The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
Letter of Amendment Date: 08 August 2018 
ACTG Network Coordinating Center 
Social & Scientific Systems, Inc.    
             Telephone: 301-628-3000 
8757 Georgia Avenue, 12th Floor      
              Fax: 301-628-3302 
Silver Spring, MD  20910 
LETTER OF AMENDMENT 
DATE: 
 August 08, 2018 
TO: 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
FROM: 
A5360 Protocol Team 
SUBJECT: 
Letter of Amendment #2 for Protocol A5360, Version 1.0, 01/10/18, 
entitled “A Single-arm Study to Evaluate the Feasibility and Efficacy of 
a Minimal Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free 
HCV Therapy to HCV Infected Populations who are HCV Treatment 
Naïve with Evidence of Active HCV Infection: The MINMON Study” 
The following information impacts the A5360 study and must be forwarded to 
your institutional review board (IRB)/ethics committee (EC) as soon as 
possible for their information and review. This Letter of Amendment (LOA) 
must be approved by your IRB/EC before implementation. 
The following information may also impact the Sample Informed Consent. Your 
IRB/EC is responsible for determining the process of informing participants of 
the contents of this LOA. 
Upon receiving final IRB/EC and any other applicable regulatory entity approvals 
for this LOA, sites should implement the LOA immediately. Sites are still 


Letter of Amendment #2 
          Page 2 of 5 
8 Aug 2018 
ACTG A5360 Protocol Version 1.0 
required to submit an LOA registration packet to the DAIDS Protocol 
Registration Office (PRO) at the Regulatory Support Center. Sites will receive a 
registration notification for the LOA once the DAIDS PRO verifies that all 
required LOA registration documents have been received and are complete. An 
LOA registration notification from the DAIDS PRO is not required prior to 
implementing the LOA. A copy of the LOA registration notification, along with 
this letter and any IRB/EC correspondence, should be retained in the site’s 
regulatory files. 
The main reasons for this LOA are to clarify the requirement that the participant 
must contact the site to report taking the last pill of study drug (SOF/VEL), 
including adding this information to the sample informed consent; to add 
information on laboratory requirements for CD4+ post-entry; and to update the 
protocol team roster. These changes were identified by the team. 
The following are changes to A5360 FINAL Version 1.0, dated 01/10/18: 
1.
Per a new regulatory requirement by the Division of AIDS (DAIDS), a Protocol
Signature Page (PSP) is appended for submission to DAIDS Protocol Registration
System (DPRS) as part of the LOA registration packet.
2.
Section 5.1.2, Administration and Duration: The first paragraph has been revised to read:
Participants will take SOF/VEL orally once daily with or without food and will receive
treatment for a duration of 12 weeks. Study staff will observe the first dose being taken
by the participant upon completion of all entry evaluations.
The site pharmacist should include numbering on the label of each bottle (e.g., 1
of 3, 2 of 3, and 3 of 3) as well as a line to document the study product completion
date on bottle 3. Participants should be instructed to open and finish one bottle of
study product at a time, starting with bottle number 1 of 3. When the participant
takes the last pill of SOF/VEL from the last bottle (i.e., bottle 3 of 3) each bottle,
he/she will be instructed to contact the site to document and/or report the completion
of the last bottle Participants will, therefore, contact a site a maximum of three times to
indicate completion of bottle. See A5360 MOPS for additional information on reporting
of treatment stop date.
3.
Section 6.3.10, Clinical Assessments, Study Treatment (Intervention) Modifications:
This section has been updated to read as follows:
When the participant takes the last tablet of each the third bottle of SOF/VEL, he/she
will be instructed to contact the site to document and/or report the treatment stop date
study product completion date. This information self-reported by the participant
should be captured on the eCRF when reported outside of and during the week 24/SVR
evaluation visit. See section 5.1.2 and A5360 MOPS for additional details.
4.
Section 6.3.12, Immunologic Studies (For HIV co-infected participants): This section
has been updated to read as follows:
CD4+
Obtain absolute CD4+ count within 90 days prior to entry from a laboratory that


Letter of Amendment #2 
          Page 3 of 5 
8 Aug 2018 
ACTG A5360 Protocol Version 1.0 
possesses a CLIA certification or equivalent. 
For post-entry evaluations, all laboratories must possess a CLIA certification 
or equivalent and must be certified for protocol testing by the DAIDS 
Immunology Quality Assurance (IQA) Program. 
5.
APPENDIX I, Sample Informed Consent (SIC), Section II Description of Study Visits:
The fifth paragraph under Entry has been revised to read as follows:
At this visit, you will be given your study drugs. The study staff will give you enough 
study drugs to last 12 weeks (3 months). Study staff will watch you take your first dose 
before leaving the site. You can take the study medication (SOF/VEL) with or without 
food. You will receive adherence education and counseling on the study drug, as 
described below. 
You will be given instructions on how to take the study medication and what to do if you 
forget to take it. There will be instructions on the study medication bottle asking 
you to call the site when you finish taking the last pill of the last bottle (bottle #3), 
or you can write the date of when you took the last pill on the label of bottle #3 
and bring the bottle with you to your week 24/SVR evaluation visit. You may also 
note the date you finished the last pill within your phone or write it down on a 
separate piece of paper, as long as you bring this date with you to your week 
24/SVR evaluation visit. You will also receive a flier with information on two types of 
other medications (proton pump inhibitors and H2 inhibitors [e.g., heartburn medication]) 
that you should not take while taking study medication. [Sites: Please include local 
names of PPIs and H2 inhibitors on a flyer to give to participants at entry. Pictures 
should also be included on the flyer.] 
6.
SIC, Section III Description of Study Evaluations: This section has been revised to read
as follows:
Study drugs distribution and storage 
You will be given a 12-week supply of study medication at entry. Study staff will watch 
you take your first dose, before you leave the site. You will be asked to store the study 
medication as instructed on the medicine bottle label. There will be instructions on the 
study medication bottle asking you to write down the date of, or call the site when, 
you finish taking the last pill of the last bottle (bottle #3). 
7.
PROTOCOL TEAM ROSTER: Update the fax numbers for Drs. Beverly Alston-Smith
and Leonard Sowah.
DAIDS Clinical Representatives 
Beverly L. Alston-Smith, MD 
Complications and Co-Infectious Research Branch 
CCRB, DAIDS, NIAID, NIH 
5601 Fishers Lane, Room 9F50, MSC #9830 
Rockville, MD  20852 
Phone: 301-435-3773 
Fax: 240-627-3107 
Email: balston@niaid.nih.gov 


Letter of Amendment #2 
          Page 4 of 5 
8 Aug 2018 
ACTG A5360 Protocol Version 1.0 
Leonard Anang Sowah, MD, MPH, FACP 
CCRB/TRP/DAIDS/NIAID/NIH/DHHS 
Therapeutics Research Program 
5601 Fishers Lane, Room 9F52B 
Rockville, MD  20852 
Phone: 301-761-7231 
Fax: 240-627-3107 
Email: leonard.sowah@nih.gov 
The information above will be incorporated into the next protocol version as necessary if the 
protocol is amended. 


Letter of Amendment #2 
          Page 5 of 5 
8 Aug 2018 
ACTG A5360 Protocol Version 1.0 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy 
to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations who are 
HCV Treatment Naïve with Evidence of Active HCV Infection: The MINMON Study 
SIGNATURE PAGE 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States 
(US) Health and Human Service regulations (45 CFR 46); applicable U.S. Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
Principal Investigator: 
Print/Type 
Signed: 
 Date:___________ 
Name/Title 


Letter of Amendment #1 
          Page 1 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
Letter of Amendment #1 for: 
A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The 
MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
NIAID CRMS # 30103 
Letter of Amendment Date: 15 June 2018 
ACTG Network Coordinating Center 
Social & Scientific Systems, Inc. 
Telephone: 301-628-3000 
8757 Georgia Avenue, 12th Floor 
Fax: 301-628-3302 
Silver Spring, MD  20910 
LETTER OF AMENDMENT 
DATE: 
June 15, 2018 
TO: 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
FROM: 
A5360 Protocol Team 
SUBJECT: Letter of Amendment #1 for Protocol A5360, Version 1.0, 01/10/18, entitled “A 
Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: 
The MINMON Study” 
The following information impacts the A5360 study and must be forwarded to your 
institutional review board (IRB)/ethics committee (EC) as soon as possible for their 
information and review. This Letter of Amendment (LOA) must be approved by your 
IRB/EC before implementation. 
The following information may also impact the Sample Informed Consent. Your IRB/EC is 
responsible for determining the process of informing participants of the contents of this 
LOA. 


Letter of Amendment #1 
          Page 2 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
Upon receiving final IRB/EC and any other applicable regulatory entity approvals for this 
LOA, sites should implement the LOA immediately. Sites are still required to submit an 
LOA registration packet to the DAIDS Protocol Registration Office (PRO) at the 
Regulatory Support Center. Sites will receive a registration notification for the LOA once 
the DAIDS PRO verifies that all required LOA registration documents have been received 
and are complete. An LOA registration notification from the DAIDS PRO is not required 
prior to implementing the LOA. A copy of the LOA registration notification, along with 
this letter and any IRB/EC correspondence, should be retained in the site’s regulatory 
files. 
Updates are being made to A5360 FINAL Version 1.0, dated 01/10/18, for the following 
reasons: 
a.
To comply with a new regulatory requirement of the Division of AIDS (DAIDS), a
signature is being added immediately after the title page and is to be submitted with the
LOA registration packet (item 9).
b.
To clarify language identified by the team and sites after the protocol was distributed to sites
on 02/14/18.
c.
To update the protocol team roster.
d.
To incorporate protocol template changes made since the protocol was distributed to the field
on 02/14/18.


Letter of Amendment #1 
          Page 3 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
TABLE OF CONTENTS 
Page 
1.
Protocol Team Roster ............................................................................................................. 4
2.
Section 6.3.4, Model for End-Stage Liver Disease (MELD) Score ......................................... 4
3.
Section 6.3.8, Medical History ................................................................................................. 5
4.
Section 6.3.10, Clinical Assessments ..................................................................................... 5
5.
Section 6.3.11, Laboratory Evaluations .................................................................................. 5
6.
Section 6.3.13, Virologic Studies ............................................................................................ 6
7.
Section 6.3.15, Questionnaires, Substance Use Questionnaire ............................................. 6
8.
Section 8.3, Pregnancy ........................................................................................................... 6
9.
Section 14.2, Participant Confidentiality ................................................................................. 6
10.
Section 14.3, Study Discontinuation ....................................................................................... 7
11.
SAMPLE INFORMED CONSENT, Risks of Study Drug .......................................................... 7
12.
SAMPLE INFORMED CONSENT, WHAT ABOUT CONFIDENTIALITY? ............................. 7
13.
Protocol Template Changes .................................................................................................... 8
14.
Signature Page ..................................................................................................................... 10


Letter of Amendment #1 
          Page 4 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
The specific changes that are being made via this LOA to A5360, Version 1.0, 02/14/18, are 
listed below. An italicized statement provides the location of the change within the identified 
section of the protocol. New text resulting from this LOA appears in bold; deleted text is shown 
in strikethrough. 
1.
Protocol Team Roster
The following team members have been added to the roster: 
Industry Representative 
Andrea Ocampo, CCRA 
Clinical Trial Manager 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
Phone: 650-358-8037 
Fax: 650-524-9872 
Email: Andrea.Ocampo@gilead.com 
Laboratory Specialist 
Allan-Michael Bills, BS 
ACTG Network Coordinating Center 
Social & Scientific Systems, Inc. 
Laboratory Science Group 
8757 Georgia Avenue, 12th Floor 
Silver Spring MD 20910 
Phone: 301-628-3273 
Fax: 301-628-3304 
Email: abills@s-3.com 
DAIDS Clinical Representative 
Leonard Anang Sowah MD, MPH, FACP 
CCRB/TRP/DAIDS/NIAID/NIH/DHHS 
Therapeutics Research Program 
5601 Fisher’s Lane, Room 9F52B 
Rockville, MD 20852 
Phone: 301-761-7231 
Fax: 301-480-4522 
Email: leonard.sowah@nih.gov 
2.
Section 6.3.4, Model for End-Stage Liver Disease (MELD) Score
The following note has been added after the first paragraph to read: 
The MELD score measures the mortality risk in participants with end-stage liver disease. It is 
used as a disease severity index to help prioritize allocation of organs for transplant. In order 
to calculate the MELD score, total bilirubin (mg/dl), sodium (mEg/L), INR, and serum 


Letter of Amendment #1 
          Page 5 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
creatinine (mg/dl) values are needed. 
NOTE: The MELD score at entry should be calculated using the INR value from 
screening. 
3.
Section 6.3.8, Medical History
The first paragraph has been updated to read:
The medical history must include all signs and symptoms regardless of grade and all
diagnoses identified by the ACTG criteria for clinical events and other diagnoses regardless
of grade within 30 days prior to entry. In addition, the following diagnoses should be
reported regardless of when the diagnosis was made:

AIDS-defining conditions (only for HIV-1 co-infected participants)

Bone fractures (verbal history accepted)

Coronary heart disease

Cancer (exclusive of basal/squamous cell skin cancer)

Diabetes

Tuberculosis

Chronic HCV (If available, appropriate documentation from medical records of
chronic HCV-infection, defined as having a documented HCV-positive antibody
serology for greater than 6 months.)

Chronic HBV

Substance use (injection, non-injection drugs, and alcohol) captured via the
WHO ASSIST instrument

HIV-1 diagnosis (for HIV-1 co-infected participants)
Any allergies to any medications and their formulations must also be documented. 
4.
Section 6.3.10, Clinical Assessments
The third paragraph located after Targeted Physical Exam has been updated to read: 
Post entry, record the following targeted events regardless of grade: 
Uterine pregnancy
AIDS-defining conditions (refer to the CDC HIV Classification and the WHO Staging
System for HIV Infection and Disease) 
Tuberculosis
Chronic HBV
Ascites
Hepatic encephalopathy
Variceal bleeding
Hepatocellular carcinoma
5.
Section 6.3.11, Laboratory Evaluations


Letter of Amendment #1 
          Page 6 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
The second sentence has been revised to read: 
At screening and entry, all laboratory values must be recorded on the eCRF. For post-entry 
assessments, all laboratory values for hemoglobin, AST, ALT, blood urea nitrogen (BUN), 
serum creatinine, total bilirubin, sodium, INR, albumin, platelets, and pregnancy test 
(regardless of grade/result) must be recorded on an eCRF. 
6.
Section 6.3.13, Virologic Studies
The last sentence has been revised to read:
HCV RNA samples on study will be processed and shipped to the designated A5360 VSL
for real-time quantitative HCV RNA analysis.
7.
Section 6.3.15, Questionnaires, Substance Use Questionnaire
The Substance Use Questionnaire paragraph has been revised to read:
The substance use questionnaire will be administered at entry, week 24/SVR evaluation,
and weeks 48 and 72 visits to solicit participant-reported information regarding use of
substances (ie, alcohol, cigarettes, drugs). The Alcohol, Smoking and Substance
Involvement Screening Test (ASSIST) survey that was developed for the WHO by an
international group of researchers and clinicians as a technical tool to assist with early
identification of substance use-related health risks and substance use disorders will be
used. This tool has been validated globally and captures information on alcohol, smoking,
and injection and non-injection drug use.
See the A5360 MOPS for further details.
8.
Section 8.3, Pregnancy
The first paragraph has been revised to read:
Pregnancy will result in immediate discontinuation of the study medication and initiation of
counseling regarding the lack of information on safety of SOF/VEL in pregnancy.
Participants who become pregnant while on study should contact the site to schedule an
unplanned study visit (only up to week 22) and will be followed on study/off-treatment until
study completion. A visit following the end of pregnancy will be conducted for evidence of
AEs in the participant, and an outcome eCRF will be completed. Male participants whose
partners become pregnant will continue treatment and should continue to follow the
study procedures as outlined in the SOE. No additional reporting or monitoring is
required for male participants’ partners who become pregnant.
9.
Section 14.2, Participant Confidentiality
The first paragraph has been revised to remove mention of “FDA” since this is a Non-IND


Letter of Amendment #1 
          Page 7 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
study. 
All laboratory specimens, evaluation forms, reports, and other records that leave the site will 
be identified by coded number only to maintain participant confidentiality. All records will be 
kept locked. All computer entry and networking programs will be done with coded numbers 
only. Clinical information will not be released without written permission of the participant, 
except as necessary for monitoring by the ACTG, IRB/EC, FDA, NIAID, OHRP, other local, 
US, and international regulatory entities as part of their duties, or the industry supporter(s) or 
designee. 
10. Section 14.3, Study Discontinuation
The first paragraph has been revised to remove mention of “FDA” since this is a Non-IND
study.
The study may be discontinued at any time by the ACTG, IRB/EC, FDA, NIAID, OHRP,
other country-specific government agencies as part of their duties to ensure that research
participants are protected, or the industry supporter.
11. SAMPLE INFORMED CONSENT, Risks of Study Drug
The second paragraph has been revised to read:
SOF/VEL has limited drug interactions with HIV medications with the exception of three HIV
medications- efavirenz, tenofovir, etravirine, and tipranavir/ritonavir. If you are taking any of
these medications, your doctor will talk to you about these interactions in detail and what
symptoms to look out for. Your doctor may modify your HIV medications after discussing it
with you so that you can be included in this study.
12. SAMPLE INFORMED CONSENT, WHAT ABOUT CONFIDENTIALITY?
The second and sixth paragraphs have been revised to read:
Your records may be reviewed by the US Food and Drug Administration (FDA), the ACTG,
the US Office for Human Research Protections (OHRP), or other local, US, and international
regulatory entities as part of their duties (insert name of site) institutional review board (IRB)
(a committee that protects the rights and safety of participants in research), National
Institutes of Health (NIH), study staff, study monitors, drug companies supporting this study,
and their designees. Having a Certificate of Confidentiality does not prevent you from
releasing information about yourself and your participation in the study.
Your records may be reviewed by the US FDA, the ACTG, the US Office for Human
Research Protections (OHRP), or other local, US, and international regulatory entities as
part of their duties, (insert name of site) institutional review board (IRB) or Ethics Committee
(a committee that protects the rights and safety of participants in research), National
Institutes of Health (NIH), study staff, study monitors, drug companies supporting this study,
and their designees.


Letter of Amendment #1 
          Page 8 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
13. Protocol Template Changes
The following changes to the protocol template since final Version 1.0 of the protocol went to
the field on 02/14/18 have also been made:
a.
Section 6.3, Instructions for Evaluations
Updated link to Source Document Guidelines on the DAIDS website- 
https://www.niaid.nih.gov/sites/default/files/daids-sourcedocpolicy.pdf.
b.
Section 6.3.10, Clinical Assessments
The following sentence has been added after the list of targeted events to record
regardless of grade (as found after targeted physical exam):
Post entry, see section 8.3 for collection requirements for pregnancy.
c.
Section 7.4, Study Monitoring
The first sentence of the second paragraph has been revised to read:
The DAIDS clinical representative will review and assess select EAE reports for
potential impact on the study participant safety and protocol conduct as per DAIDS
policies, guidance documents, and SOPs as applicable.
d.
Section 9.2, Premature Study Discontinuation
The third bullet has been removed:

Request by the participant to withdraw.

Request of the primary care provider if s/he thinks the study is no longer in the best
interest of the participant.
 Participant judged by the investigator to be at significant risk of failing to comply with
the provisions of the protocol as to cause harm to self or seriously interfere with the 
validity of the study results. 

At the discretion of the IRB/Ethics Committee, Food and Drug Administration (FDA),
NIAID, Office for Human Research Protections (OHRP), other government agencies
as part of their duties, investigator, or industry supporter.


Letter of Amendment #1 
          Page 9 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
e.
Section 13.3, Clinical Site Monitoring and Record Availability
Section 13.3.2 has been revised to read:
The site investigator will make study documents (e.g., consent forms, drug distribution
forms, eCRFs) and pertinent hospital or clinic records readily available for inspection by
the local IRB, the site monitors, the FDA, the NIAID, the OHRP, the industry supporter
or designee, and other local, US, and international regulatory entities for confirmation
of the study data.
The information above will be incorporated into the next protocol version as necessary if 
the protocol is amended. 


Letter of Amendment #1 
          Page 10 of 10 
15 Jun 2018 
ACTG A5360 Protocol Version 1.0 
14. Signature Page
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy to 
Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations who are HCV 
Treatment Naïve with Evidence of Active HCV Infection: The MINMON Study 
SIGNATURE PAGE 
I will conduct the study in accordance with the provisions of this protocol and all applicable protocol-
related documents. I agree to conduct this study in compliance with United States (US) Health and 
Human Service regulations (45 CFR 46); applicable U.S. Food and Drug Administration regulations; 
standards of the International Conference on Harmonization Guideline for Good Clinical Practice (E6); 
Institutional Review Board/Ethics Committee determinations; all applicable in-country, state, and local 
laws and regulations; and other applicable requirements (e.g., US National Institutes of Health, Division 
of AIDS) and institutional policies. 
Principal Investigator: 
Print/Type 
Signed: 
Date:  
  Name/Title 


A5360 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal 
Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV 
Infected Populations who are HCV Treatment Naïve with Evidence of Active HCV 
Infection: The MINMON Study 
A Multicenter Trial of the AIDS Clinical Trials Group (ACTG) 
Sponsored by: 
The National Institute of Allergy 
and Infectious Diseases 
Industry Support Provided by: 
Gilead Sciences, Inc. 
IND # 
The ACTG Hepatitis Transformative Science Group: 
Mark Sulkowski, MD, Chair 
Protocol Chair: 
Sunil Solomon, MBBS, PhD, MPH  
Protocol Vice-Chairs: 
Mark Sulkowski, MD 
Sandra Wagner Cardoso, MD, PhD 
DAIDS Clinical Representative: 
Beverly Alston-Smith, MD 
Clinical Trials Specialists: 
Chanelle Houston, BS 
Jennifer Tiu, MPH 
FINAL Version 1.0 
January 10, 2018 


A5360 
FINAL Version 1.0 
01/10/18 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring 
Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected 
Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The 
MINMON Study 
SIGNATURE PAGE 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations (45 CFR 46); applicable U.S. Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
Principal Investigator: _______________________________________________ 
Print/Type 
Signed: ___________________________________ Date: _____________ 
 Name/Title


A5360 
FINAL Version 1.0 
01/10/18 
TABLE OF CONTENTS 
Page 
SIGNATURE PAGE .................................................................................................................... 2 
SITES PARTICIPATING IN THE STUDY .................................................................................... 5 
PROTOCOL TEAM ROSTER ..................................................................................................... 6 
STUDY MANAGEMENT ........................................................................................................... 10 
GLOSSARY OF PROTOCOL-SPECIFIC TERMS ..................................................................... 12 
SCHEMA .................................................................................................................................. 14 
1.0 
HYPOTHESIS AND STUDY OBJECTIVES ................................................................... 16 
1.1 
Hypothesis ......................................................................................................... 16 
1.2 
Primary Objectives ............................................................................................. 16 
1.3 
Secondary Objectives ........................................................................................ 16 
1.4 
Exploratory Objectives ....................................................................................... 16 
2.0 
INTRODUCTION ........................................................................................................... 17 
2.1 
Background ........................................................................................................ 17 
2.2 
Rationale ........................................................................................................... 24 
3.0 
STUDY DESIGN ........................................................................................................... 28 
4.0 
SELECTION AND ENROLLMENT OF PARTICIPANTS ................................................ 29 
4.1 
Inclusion Criteria (Step 1) ................................................................................... 29 
4.2 
Exclusion Criteria (Step 1) ................................................................................. 33 
4.3 
Inclusion Criteria (Step 2) ................................................................................... 34 
4.4 
Exclusion Criteria (Step 2) ................................................................................. 34 
4.5 
Study Enrollment Procedures............................................................................. 34 
4.6 
Co-enrollment Guidelines ................................................................................... 35 
5.0 
STUDY TREATMENT ................................................................................................... 36 
5.1 
Regimens, Administration, and Duration ............................................................ 36 
5.2 
Study Product Formulation and Preparation ....................................................... 36 
5.3 
Pharmacy: Product Supply, Distribution, and Accountability .............................. 37 
5.4 
Concomitant Medications ................................................................................... 37 
6.0 
CLINICAL AND LABORATORY EVALUATIONS ........................................................... 38 
6.1 
Schedule of Evaluations..................................................................................... 38 
6.2 
Timing of Evaluations ......................................................................................... 42 
6.3 
Instructions for Evaluations ................................................................................ 44 
7.0 
ADVERSE EVENTS AND STUDY MONITORING ......................................................... 54 
7.1 
Definition of Adverse Events .............................................................................. 54 
7.2 
Adverse Event Collection Requirements for This Protocol ................................. 54 
7.3 
Expedited Adverse Event (EAE) Reporting to DAIDS ........................................ 55 
7.4 
Study Monitoring ................................................................................................ 56 
8.0 
CLINICAL MANAGEMENT ISSUES .............................................................................. 56 
8.1 
Toxicity .............................................................................................................. 56 
8.2 
Management of Side Effects of SOF/VEL .......................................................... 57 
8.3 
Pregnancy.......................................................................................................... 57 


A5360 
 
 
FINAL Version 1.0 
 
 
01/10/18 
 
 
CONTENTS (Cont’d) 
Page 
 
9.0 
CRITERIA FOR DISCONTINUATION ........................................................................... 58 
9.1 
Permanent and Premature Treatment Discontinuation ....................................... 58 
9.2 
Premature Study Discontinuation ....................................................................... 58 
10.0 
STATISTICAL CONSIDERATIONS ............................................................................... 58 
10.1 
General Design Issues ....................................................................................... 58 
10.2 
Outcome Measures ............................................................................................ 59 
10.3 
Registration and Stratification ............................................................................ 60 
10.4 
Sample Size and Accrual ................................................................................... 60 
10.5 
Data and Safety Monitoring ................................................................................ 63 
11.0 
PHARMACOLOGY PLAN .............................................................................................. 66 
12.0  
COST-BENEFIT ANALYSIS PLAN ................................................................................ 66 
12.1  
Objective ............................................................................................................ 66 
12.2 
Primary Outcome ............................................................................................... 66 
12.3 
General Approach to Costing ............................................................................. 66 
12.4  
Resource Utilization Data Collection .................................................................. 68 
12.5 
Assessing SVR Status ....................................................................................... 68 
12.6  
Estimation of Cost/SVR Outcome ...................................................................... 69 
13.0 
DATA COLLECTION AND MONITORING ..................................................................... 69 
13.1 
Records to Be Kept ............................................................................................ 69 
13.2 
Role of Data Management ................................................................................. 69 
13.3 
Clinical Site Monitoring and Record Availability .................................................. 70 
14.0 
PARTICIPANTS ............................................................................................................ 70 
14.1 
Institutional Review Board (IRB) Review and Informed Consent ........................ 70 
14.2 
Participant Confidentiality ................................................................................... 70 
14.3 
Study Discontinuation ........................................................................................ 70 
15.0 
PUBLICATION OF RESEARCH FINDINGS .................................................................. 71 
16.0 
BIOHAZARD CONTAINMENT ...................................................................................... 71 
17.0 
REFERENCES .............................................................................................................. 72 
APPENDIX I: SAMPLE INFORMED CONSENT ....................................................................... 74 
 
 


 
5 
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01/10/18 
 
SITES PARTICIPATING IN THE STUDY 
 
A5360 is a multicenter study open to all US and non-US clinical research sites (CRSs). 
 
 
 


 
6 
A5360 
 
 
FINAL Version 1.0 
 
 
01/10/18 
PROTOCOL TEAM ROSTER 
 
Chair 
Sunil Suhas Solomon, MBBS PhD MPH 
Johns Hopkins University School of 
Medicine 
1830 E. Monument Street, Room 444 
Baltimore, MD 21287  
Phone: 443-287-9596 
Email: sss@jhmi.edu  
 
Vice-chairs 
Mark S. Sulkowski, MD 
Johns Hopkins University School of 
Medicine 
1830 E. Monument Street, Room 445 
Baltimore, MD 21287  
Phone: 410-614-4172 
Email: msulkowski@jhmi.edu 
 
Sandra Wagner Cardoso, MD, PhD 
National Institute of Infectious Diseases,  
Oswaldo Cruz Foundation (Fiocruz) 
Av. Brasil 4365 Manguinhos 
Rio de janeiro-RJ – 21040-360 
Brazil 
Phone: +55 21 38659623 
Email: Sandra.wagner@ini.fiocruz.br  
 
DAIDS Clinical Representative  
Beverly L. Alston-Smith, MD 
Complications and Co-Infectious Research 
Branch  
CCRB, DAIDS, NIAID, NIH 
5601 Fishers Lane, Room 9F50 MSC #9830 
Rockville, MD  20852 
Phone: 301-435-3773 
Fax: 301-480-4522 
Email: balston@niaid.nih.gov  
 
Clinical Trials Specialists 
Chanelle Houston, BS 
ACTG Network Coordinating Center 
Social & Scientific Systems, Inc. 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD 20910-3714 
Phone: 301-628-3367 
Fax: 301-628-3302 
Email: CHouston@s-3.com  
 
Jennifer Tiu, BS, MPH 
ACTG Network Coordinating Center 
Social & Scientific Systems, Inc. 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD 20910-3714 
Phone: 301-628-3371 
Fax: 301-628-3302 
Email: JTiu@s-3.com  
 
Statisticians 
Laura Smeaton, MS 
Statistical and Data Analysis Center 
Harvard TH Chan School of Public Health 
FXB Building, Room 511 
651 Huntington Avenue 
Boston, MA 02115-6017 
Phone: 617-432-2525 
Fax: 617-432-3163 
Email: smeaton@sdac.harvard.edu  
 
Vincent Vu, MPH 
Statistical and Data Analysis Center 
Harvard TH Chan School of Public Health 
FXB Building, Room 508 
651 Huntington Avenue 
Boston, MA 02115-6017 
Phone: 617-432-1352 
Fax: 617-432-3163 
Email: vvu@sdac.harvard.edu


 
7 
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PROTOCOL TEAM ROSTER (Cont’d) 
01/10/18 
 
Data Managers 
Laura Weichmann, MPH 
Frontier Science & Technology Research 
Foundation, Inc. 
4033 Maple Road 
Amherst, NY 14226-1056 
Phone: 716-834-0900 Ext. 7281 
 
Fax: 716-834-8675 
Email: weichman@fstrf.org  
 
Christine Scello, MA 
Frontier Science & Technology Research 
Foundation, Inc. 
4033 Maple Road 
Amherst, NY 14226-1056 
Phone: 716-834-0900 Ext. 7233 
 
Fax: 716-834-8432 
Email: scello@fstrf.org 
 
DAIDS Pharmacist 
Oladapo Alli, PharmD 
Pharmaceutical Affairs Branch 
DAIDS, OSCO, NIAID, NIH 
5601 Fishers Lane 
Room 9E16 MSC #9830 
Rockville, MD 20892 
Phone: 240-627-3593 
Fax: 240-627-3112 
Email: oladapo.alli@nih.gov  
 
Immunologist  
Donald Anthony, MD, PhD 
Case CRS 
Department of Medicine 
Biomedical Research, Building 1028 
2109 Adelbert Road 
Cleveland, OH 44106 
Phone: 216-368-3540 
Fax: 216-368-2034 
Email: dda3@case.edu 
Virologist  
David Wyles, MD 
University of Colorado Hospital CRS 
P.O. Box 6511 
Aurora, CO 80045 
Phone: 303-602-5148 
Email: david.wyles@dhha.org  
 
Pharmacologists  
Gene Morse, PharmD 
University of Rochester Adult HIV 
Therapeutic Strategies Network CRS 
701 Ellicott Street 
Buffalo, NY 14203 
Phone: 716-881-7464 
Email: emorse@buffalo.edu 
 
Charles Venuto, PharmD 
University of Rochester Adult HIV 
Therapeutic Strategies Network CRS 
265 Crittenden Boulevard 
Rochester NY 14642 
Phone: 585-276-5622 
Email: charles.venuto@chet.rochester.edu  
 
Investigators 
Anchalee Avihingsanon, MD, PhD 
Thai Red Cross AIDS Research Center 
Treatment (TRC-ARC Treatment) CRS  
104 Rajdamri Road  
Patumwan, Bangkok 10330 
Thailand 
Phone: +66-8-68128889 
Email: anchaleea2009@gmail.com  
 
Benjamin P. Linas, MD, MPH 
Boston Medical Center ACTG CRS 
1 Boston Medical Center Place 
Crosstown Building Room 2007 
Boston, MA 02118 
Phone: 617-414-5238  
Email: Benjamin.Linas@bmc.org 


 
8 
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FINAL Version 1.0 
 
PROTOCOL TEAM ROSTER (Cont’d) 
01/10/18 
 
Investigators (Cont’d) 
Susanna Naggie, MD, MHS 
Duke University School of Medicine 
2400 Pratt St., Rm. 0311 Terrace Level 
Durham, NC 27705 
Phone: 919-684-2584 
Email: susanna.naggie@duke.edu 
 
Gregory Robbins, MD, MPH 
Massachusetts General Hospital CRS 
Infectious Disease Unit 
55 Fruit Street, Cox 5 
Boston, MA 02114 
Phone: 617-724-0076 
Fax: 617-742-4795 
Email: grobbins@partners.org  
 
Field Representative 
Dimas Kliemann, MD 
Hospital Nossa Senhora da Conceicao CRS  
Servico de Infectologia 
Av. Francisco Trein, 596 
Cristo Redentor 
Porto Alegre 91350-200 
Rio Grande do Sul, Brazil 
Phone: +55-51-33572126 
Email: dimaskliemann@gmail.com 
 
Laboratory Technologists 
Christopher Lane, AAS 
University of Rochester Adult HIV 
Therapeutic Strategies Network CRS 
Infectious Diseases Division 
Department of Medicine 
Box 689 
601 Elmwood Avenue 
Rochester NY 14642 
Phone: 585-276-5574  
Fax: 585-442-9328 
Email: 
christopher_lane@urmc.rochester.edu
Laboratory Technologists, cont’d 
Sasiwimol Ubolyam, MSc 
Thai Red Cross AIDS Research Center 
Treatment (TRC-ARC Treatment) CRS 
104 Rajdamri Road 
Patumwan Bangkok 10330 
Thailand 
Phone: +66-2-2564648 
Email: sasiwimol.u@hivnat.org  
 
Community Scientific Subcommittee (CSS) 
Representative 
Angel L. Hernandez, BA 
Puerto Rico AIDS Clinical Trials Unit CRS 
Barrio Saltos 
Road 566 Int Road 593, KM 0.2 
Orocovis, PR 00720 
Phone: 787-919-6145 
Email: angelhdz2863@gmail.com  
 
International Site Specialist 
Carolyn Davidson, BS 
ACTG Network Coordinating Center 
Social & Scientific Systems, Inc. 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD 20910-3714 
Phone: 301-628-3235 
Fax: 301-628-3302 
Email: CDavidson@s-3.com  
 
Industry Representatives 
Betty Chiang, MD 
Gilead Science, Inc. 
333 Lakeside Drive 
Foster City, CA 94404  
Phone: 646-483-5950 
Email: Betty.Chiang@gilead.com  
 
Joe Llewellyn, PharmD 
Associate Director, Hepatitis C  
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404   
Phone: 650-235-3725  
Email: Joe.Llewellyn@gilead.com


 
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Industry Representatives, Cont’d 
Annie Son, BA 
Sr. Medical Affairs Associate 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
Phone: 650-378-2175 
Email: Annie.Son@gilead.com 
 
Laboratory Data Manager 
Laura Hovind, MS 
Frontier Science & Technology Research 
Foundation, Inc. 
4033 Maple Road 
Amherst, NY 14226-1056 
Phone: 76-834-0900 Ext. 7468 
Fax: 716-33-0655 
Email: hovind@fstrf.org 


 
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STUDY MANAGEMENT 
 
All general questions concerning this protocol should be sent to actg.coreA5360@fstrf.org via 
email. The appropriate team member will respond with a "cc" to actg.coreA5360@fstrf.org. A 
response should generally be received within 24 hours (Monday-Friday). 
 
Protocol Email Group 
Sites should contact the User Support Group at the Data Management Center (DMC) as soon 
as possible to have the relevant personnel at the site added to the actg.protA5360 email group. 
Include the protocol number in the email subject line.  
• 
  Send an email message to actg.user.support@fstrf.org  
 
Clinical Management  
For questions concerning entry criteria, toxicity management, concomitant medications, and co-
enrollment, contact the protocol team. 
• 
Send an email message to actg.coreA5360@fstrf.org. Include the protocol number, patient 
identification number (PID), and a brief relevant history. 
 
Laboratory 
For questions specifically related to immunologic, virologic, or pharmacologic laboratory tests, 
contact the protocol immunologist, virologist, or pharmacologist.  
• 
Send an email message to actg.coreA5360@fstrf.org (ATTN: Donald Anthony- 
immunologist; David Wyles- virologist; Gene Morse, Charles Venuto- pharmacologists). 
 
Data Management 
• 
For nonclinical questions about transfers, inclusion/exclusion criteria, electronic case report 
forms (eCRFs), registration, and other data management issues, contact the data manager. 
Electronic CRFs (eCRFs) completion guidelines and participant completed CRFs can be 
downloaded from the FSTRF website at www.frontierscience.org. 
• 
For transfers, reference the Study Participant Transfer SOP 119, and contact Laura 
Weichmann, weichman@fstrf.org, and Christine Scello, scello@fstrf.org, directly.  
• 
For other questions, send an email message to actg.coreA5360@fstrf.org (ATTN: Laura 
Weichmann and Christine Scello).  
• 
Include the protocol number, PID, and a detailed question. 
 
Participant Registration 
For participant registration questions or problems and study identification number SID lists.  
• 
Send an email message to rando.support@fstrf.org or call the Statistical and Data Analysis 
Center (SDAC)/DMC Randomization Desk at 716-834-0900, extension 7301.  
 
DMC Portal and Medidata Rave Problems  
Contact DMC User Support: 
• 
Send an email message to actg.support@fstrf.org or call 716-834-0900 x7302. 
 


 
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Protocol Document Questions 
For questions concerning the protocol document, contact the Clinical Trials Specialists.  
• 
Send an email message to actg.coreA5360@fstrf.org (ATTN: Chanelle Houston, 
CHouston@s-3.com, and Jennifer Tiu, JTiu@s-3.com). 
 
Copies of the Protocol 
To request a hard copy of the protocol, send a message to ACTGNCC@s-3.com (ATTN: Diane 
Delgado). Electronic copies can be downloaded from the ACTG Website 
(https://www.actgnetwork.org). 
 
Product Package Inserts and/or Investigator Brochures 
To request copies of product package inserts or investigator brochures, contact the DAIDS 
Regulatory Support Center (RSC) at RIC@tech-res.com or call 301-897-1708. 
 
Protocol Registration 
For protocol registration questions, send an email message to Protocol@tech-res.com or call 
301-897-1707.  
 
Protocol Activation 
For questions related to protocol activation, contact the Clinical Trials Specialists (Chanelle 
Houston, CHouston@s-3.com, and Jennifer Tiu, JTiu@s-3.com) or ACTG Site Coordination 
group at actgsitecoordination@s-3.com.  
 
Study Product 
For questions or problems regarding study product, dose, supplies, records, and returns, email 
Oladapo Alli, protocol pharmacist, at oladapo.alli@nih.gov.  
 
Study Drug Orders 
Call the Clinical Research Products Management Center (CRPMC) at 301-294-0741. 
 
IND (Investigational New Drug) Number or Questions  
The IND number will be available on the PSWP within 30 days of the submission to the FDA. 
For any questions related to the IND submission, contact the DAIDS RSC at Regulatory@tech-
res.com or call 301-897-1706. 
 
Expedited Adverse Event (EAE) Reporting/Questions  
Contact DAIDS through the RSC Safety Office at DAIDSRSCSafetyOffice@tech-res.com or call 
1-800-537-9979 or 301-897-1709; or fax 1-800-275-7619 or 301-897-1710.  
 
Phone Calls 
Sites are responsible for documenting any phone calls made to A5360 team members. 
• 
Send an email to actg.coreA5360@fstrf.org. 
 
Protocol-Specific Web Page (PSWP) 
Additional information about management of the protocol can be found on the PSWP. 


 
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GLOSSARY OF PROTOCOL-SPECIFIC TERMS 
 
AASLD 
American Association for the Study of Liver Diseases  
APRI  
Aspartate Aminotransferase to Platelet Ratio Index 
ARVs  
Antiretrovirals 
ATV 
 
atazanavir 
BIDS  
Brazilian Infectious Diseases Society 
CI 
 
confidence Interval  
CTP Score 
Child-Turcotte-Pugh Score 
CT Scan 
computerized tomography scan 
DCV 
 
daclatasvir 
DAA 
 
directly acting antivirals 
EASL   
European Association for the Study of the Liver 
EOT 
 
end of treatment 
FDC 
 
fixed dose combination 
FIB-4  
Fibrosis-4 
GFR 
 
glomerular filtration rate 
GT 
 
genotype 
HbA1C 
hemoglobin A1C 
HBcAb  
hepatitis B Virus core antibody total  
HBsAb  
hepatitis B Virus surface antibody  
HBsAg  
hepatitis B Virus surface antigen  
ICH 
 
International Council for Harmonization 
IDSA  
Infection Diseases Society of America 
IgG 
 
immunoglobulin G 
INR    
international normalized ratio 
IU 
 
international units 
LDV 
 
ledipasvir 
LLOQ   
lower limit of quantification 
LMICs   
low- and middle-income countries 
LTFU  
lost to follow-up 
MedDRA  
Medical Dictionary of Regulatory Activities System Organ Class 
MELD  
Model for End-Stage Liver Disease 
MINMON 
Minimal monitoring  
MRI 
 
Magnetic Resonance Imaging 
NI 
 
non-inferiority  


 
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PEG-IFN 
pegylated interferon  
PCR 
 
polymerase chain reaction 
PPI 
 
proton pump inhibitor  
PR 
 
pegylated interferon/ribavirin 
PSWP  
Protocol-Specific Web Page 
PT   
 
post-treatment 
RAPs   
resistance-associated polymorphisms 
RASs   
resistance-associated substitutions  
RBV 
 
ribavirin   
SMV 
 
simeprevir 
SOC 
 
standard of care 
SOF 
 
sofosbuvir 
SOF/VEL 
sofosbuvir/velpatasvir fixed dose combination  
SVR 
sustained virologic response (defined as HCV RNA <LLOQ at least 12 weeks 
after the EOT) 
ULN 
upper limit of the normal range  
VEL 
 
velpatasvir 
VL 
 
viral load 
WHO  
World Health Organization 
 


 
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SCHEMA 
 
 
A5360 
 
A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy to 
Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations who are HCV 
Treatment Naïve with Evidence of Active HCV Infection: The MINMON Study 
 
DESIGN 
This is a phase IV open-label, multicenter, prospective study to assess 
the feasibility and efficacy of a minimal monitoring (MINMON) approach in 
active hepatitis C virus (HCV)-infected, treatment naïve participants, with 
and without HIV-1 co-infection, and with no cirrhosis or with compensated 
cirrhosis only. This study will enroll a cohort of participants with active 
HCV-infection to follow a minimal monitoring protocol, at US and non-US 
sites:  
 
 
No pre-treatment HCV genotyping;  
 
Entire treatment course (84 tablets) given to participants at entry; 
 
No scheduled on-treatment laboratory monitoring or clinic visits; 
 
Remote contact with participants at week 4 (adherence counseling 
and locator update) and week 22 (scheduling of SVR visit and locator 
update). 
 
Participants will receive the fixed-dose combination (FDC) of 
sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks.   
 
DURATION 
72 weeks (see schematic diagram below) 
 
SAMPLE SIZE 
400 participants  
 
 
 
POPULATION 
Men and women aged 18 years or older with active HCV-infection of any 
genotype, HCV treatment naïve, with or without HIV-1 co-infection. 
Persons with either compensated cirrhosis or without evidence of 
cirrhosis are eligible.  
 
STRATIFICATION 
The study will use stratification factors to limit enrollment by certain 
subgroups. These stratification factors include geographical location 
(limited to no more than 132 participants enrolled from sites in the US 
within the overall study sample), HIV-1 infection (limited to no more than 
200 participants being HIV-1 positive within the overall study sample), 
and cirrhosis status (limited to no more than 80 participants within the 
overall study sample having compensated cirrhosis). There are no 
additional restrictions regarding participants who are both HIV-co-infected 
and have compensated cirrhosis, and or/geographical distribution of 
those participants. 
 


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1.0 
HYPOTHESIS AND STUDY OBJECTIVES 
1.1 
Hypothesis 
 
1.1.1  A MINMON strategy to deliver interferon and ribavirin (RBV)-free pan-genotypic 
therapy to participants with active HCV infection who are HCV treatment-naïve, 
globally, will be efficacious and safe.  
 
1.2 
Primary Objectives 
 
1.2.1 To estimate SVR (defined as HCV RNA < lower limit of quantification [LLOQ] at 
least 10 weeks after the end of treatment [EOT] [which is at least 22 weeks from 
the study entry visit date]).  
 
1.2.2 To summarize the occurrence of serious adverse events (SAEs) within 24 weeks 
following study entry.  
 
1.3 
Secondary Objectives 
 
1.3.1 To estimate the proportion of participants with unplanned clinic visits prior to SVR 
evaluation. 
 
1.3.2 To summarize the occurrence of adverse events, other than SAEs, within 24 
weeks following study entry. 
 
1.3.3 To estimate the proportion of participants who prematurely discontinue HCV 
treatment. 
 
1.4 
Exploratory Objectives 
 
1.4.1 To estimate HCV re-infection among those who achieve SVR. 
 
1.4.2 To examine the regression of liver disease (measured via Fibrosis-4 [FIB-4]) 
between study entry and final study follow-up among participants who achieve 
SVR. 
 
1.4.3 To estimate the prevalence of HCV resistance-associated substitutions (RASs) 
among participants who do not achieve SVR.  
 
1.4.4 To evaluate the impact of HCV treatment on participant quality of life (QoL) and 
disability when employing a MINMON protocol. 
 
1.4.5 To evaluate the cost per person cured when employing a MINMON protocol 
among participants with active HCV-infection receiving an oral RBV-free-pan-
genotypic HCV therapy according to treatment setting. 
 


 
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1.4.6  To explore the stability of different modes of contact information with treatment 
outcomes. 
 
1.4.7 To describe the number and types of evaluations performed at unplanned visits. 
 
1.4.8 To explore the association of self-reported adherence to study treatment with 
study completion and SVR. 
 
2.0 
INTRODUCTION 
 
2.1 
Background 
 
Global HCV Epidemiology 
There are an estimated 71 million persons who are chronically infected with HCV 
globally [1]. Almost 90% of these persons reside in low-and-middle-income countries 
(LMICs). While the highest prevalence of HCV has been observed in central and East 
Asia, North Africa and the Middle East, the majority of the people chronically infected 
with HCV are believed to be residing in South and East Asia (>50 million in each; Figure 
2.1-1) [2]. India alone is estimated to be home to over 20 million HCV-1 infected 
persons.  
 
HCV has high genetic diversity with the most genetic diversity being seen in Africa. GT 1 
is most prevalent worldwide, whereas GT 3 is found more commonly in south and 
southwest Asia. GT 4 and GT 5 are almost exclusively found in north-central and 
southern Africa, respectively. Genotype 6 is found almost exclusively in southeast Asia 
[3].  
 
Figure 2.1-1: Global distribution of persons chronically infected with HCV 
Darker red colors indicate higher prevalence and the size of the circle reflects 
the absolute number of people living with HCV. 


 
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HCV treatment access has been limited in most LMICs despite the advent of directly 
acting antivirals (DAAs) since most therapy until recently demonstrated highest efficacy 
rates in GT1 infection. Unlike HIV therapy, HCV therapy has varying response rates and 
treatment duration by genotype [4]. For example, the fixed dose combination (FDC) of 
SOF and ledipasvir (SOF/LDV) that is associated with cure rates of 97% in real-world 
cohorts of GT1 patients is not recommended for use in GT3 patients [5]. Similarly, while 
12 weeks of SOF + RBV is recommended for GT1 infections, in persons infected with 
HCV GT3 the treatment duration recommended is 24 weeks [5, 6].    
 
World Health Organization (WHO)/American Association for the Study of Liver Diseases 
(AASLD)/ Infection Diseases Society of America (IDSA)/European Association for the 
Study of the Liver (EASL) HCV Treatment Guidelines 
 
AASLD/IDSA (www.hcvguidelines.org) and the EASL (www.easl.eu) guidance for 
monitoring of patients receiving HCV therapy are among the most commonly used in 
clinical practice (Table 2.1-1), given that treatment was not available outside of US and 
Europe until mid-2015. The 2014 WHO treatment guidelines, the first guidance on 
management of HCV disease released by the WHO, were based on AASLD and EASL 
recommendations and drug-registration literature available at that time. Preferable 
regimens according to the 2014 WHO guidelines are essentially interferon-based [7]. 
Since the WHO issued these first guidelines in 2014, several new medicines for the 
treatment of HCV infection have been introduced. Of these, daclatasvir (DCV), ledipasvir  
(LDV), and a combination of ombitasvir, paritaprevir and dasabuvir were added to the 
WHO Model List of Essential Medicines in 2015 [8]. Currently, the regimens 
recommended by WHO, and other country-specific treatment guidelines are guided by 
genotype and the future incorporation of these new drugs will probably need new 
guidance in terms of monitoring treatment.  
 
Table 2.1-1: Monitoring schedule recommended by the various guidelines 
 
Monitoring Evaluations 
AASLD/IDSA 
EASL 
WHO  
Baseline genotyping 
X 
X 
X 
Baseline HCV RNA 
X 
X 
X 
Baseline labs (for liver disease staging) 
X 
X 
X 
2-week HCV RNA 
 
X 
 
2-week safety labs 
 
X 
 
4-week HCV RNA 
X 
X 
 
4-week safety labs 
X 
X 
X 
6-week HCV RNA 
X1 
 
 
8-week safety labs 
X2 
X 
 
12-week HCV RNA2 (EOT) 
X2 
X 
 
12-week safety labs2 
X2 
X 
 


 
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Monitoring Evaluations 
AASLD/IDSA 
EASL 
WHO  
16-week HCV RNA (EOT + 4) 
 
 
 
24 week HCV RNA (SVR 12) 
X 
X 
X 
1Repeat HCV RNA at 6 week if 4 week HCV RNA is detectable 
2The following tests are recommended as clinically indicated 
3Phone contact is recommended during the treatment duration to ensure optimal 
adherence 
 
Because the 2014 WHO guidelines primarily include Interferon-based regimens, the 
proposed monitoring process is intensive [7]. More recent monitoring guidelines can be 
found in the February 2016 AASLD/IDSA guidelines [9], which recommend visits or 
telephone contact as clinically indicated during treatment to ensure medication 
adherence and to monitor for adverse events and potential drug-drug interactions with 
newly prescribed medications. Complete blood count (CBC), creatinine level, calculated 
glomerular filtration rate (GFR), and hepatic function panel are recommended after 4 
weeks of treatment and as clinically indicated. Quantitative HCV viral load testing is 
recommended after 4 weeks of therapy and at 12 weeks following completion of therapy. 
If HCV RNA is detectable at week 4 of treatment, repeat quantitative HCV RNA viral load 
testing is recommended after 2 additional weeks of treatment (i.e., week 6). If 
quantitative HCV viral load has increased by greater than 10-fold (>1 log10 international 
units [IU]/mL) on repeat testing at week 6 (or thereafter), then discontinuation of HCV 
treatment is recommended. The significance of a positive HCV RNA test result at week 4 
that remains positive but lower at week 6 or week 8 is unknown. No recommendation is 
provided regarding whether to stop therapy or extend therapy in this rare clinical 
situation [1].  
 
While the WHO in their 2016 guidelines recommend a simpler monitoring protocol when 
using interferon and RBV-free DAAs for the monitoring of HCV therapy [8], their 
recommendations have never been implemented in clinical care settings and are based 
on the assumption that simplification of monitoring will not adversely impact the safety 
and efficacy of treatment. To date, minimal monitoring has not been validated in any 
setting. Indeed, clinicians in LMICs have also, to date, largely followed the AASLD and 
EASL guidelines when delivering HCV therapy. As such, the impact of the reduced 
clinical contact and on-treatment monitoring remains unknown at this time.  
 
Monitoring of HCV Therapy in Brazil 
The current Brazilian guidelines for HCV and co-infections management were released 
on June 2015 [10]. In general, following diagnosis by the presence of HCV antibodies, 
HCV RNA quantification is performed to confirm the diagnosis and repeated before 
treatment initiation. The measurement of HCV RNA is recommended at week 4 of 
treatment as a futility rule if the regimen is pegylated interferon (PEG-
IFN)/RBV/daclatasvir (DCV). Also, HCV RNA at the end of the treatment (i.e., week 12) 
and 12 weeks after the end of treatment are indicated to define SVR. HCV genotyping is 
performed if the participant fulfills the criteria to start treatment in order to define the 
genotype-specific regimen. Liver biopsy, FibroScan or Aspartate Aminotransferase to 
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(DAA naïve, HCV monoinfected patients with Metavir F3 or F4, cirrhosis identified 
clinically or by ultrasound, cryoglobilinemia, among others). HIV co-infected patients are 
eligible for treatment regardless of the presence of fibrosis. The available DAAs currently 
distributed free of charge by the Ministry of Health are SOF, DCV and simeprevir (SMV). 
Distribution of DAA started in the beginning of 2016, so there has been very little 
experience with monitoring associated with these regimens. The Brazilian guidelines 
include recommendation for routine laboratory evaluation of chronic HCV, with and 
without cirrhosis, as well as for liver cancer screening but do not have specific 
recommendations in terms of treatment follow-up aside from HCV RNA. In clinical 
practice, standard monitoring of HCV therapy will depend on the modality of treatment 
and physician expertise. According to the Brazilian Infectious Diseases Society (BIDS) 
recommendation, treatment monitoring should include serum chemistries (i.e., AST, 
ALT, GGT, Alkaline phosphatase, bilirubin prothrombin and albumin), renal function (i.e., 
creatinine, blood urea nitrogen), CBC, glucose, sodium and potassium as minimum 
monitoring for safety at the end of the first month of treatment. Additional laboratory 
evaluations should be done according to specific patient needs, as well as repeated, if 
clinically necessary. In terms of viral response, the BIDS suggestion is to repeat HCV 
RNA PCR (polymerase chain reaction) at week 4 in order to evaluate adherence and at 
post-treatment weeks 12 and 24 to evaluate SVR [11].   
 
Table 2.1-2: Standard monitoring practices currently being followed in the study 
settings for SOF-based DAA regimens 
Standard Monitoring Evaluations 
Brazil 
India 
Thailand 
United States 
Baseline genotyping 
X 
X 
X 
X 
Baseline HCV RNA 
X 
X 
X 
X 
Baseline labs (for liver disease 
staging) 
X 
X 
X 
X 
4-week HCV RNA 
X 
 
X 
X 
4-week safety labs 
X 
X 
X 
X 
6-week HCV RNA1 
 
 
 
X 
8-week safety labs 
X 
X 
X 
X 
12-week HCV RNA (EOT) 
X 
X 
 
X 
12-week safety labs 
X 
X 
X 
X 
16-week HCV RNA (EOT + 4) 
 
 
 
X2 
24 week HCV RNA (SVR 12) 
X 
X 
X 
X 
1Six week HCV RNA recommended if HCV RNA is detectable at week 4. 
2In some US settings, SVR4 is performed. 
 
Monitoring of HCV Therapy in India 
Clinicians in India treating HCV-infected patients, primarily medical gastroenterologists, 
follow the Indian National Association for the Study of Liver guidelines [12]. There is no 
special training for infectious diseases such as a fellowship following residency in India 
and most infectious diseases are treated by internists. Until December 2015, SOF, 
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available in India. As of December 2015, DCV and LDV have also become available. 
The standard practice for initiation of HCV therapy are quantification of HCV RNA 
following diagnosis by the presence of HCV antibodies, and HCV genotyping if HCV 
RNA is detected. Given the majority of patients (>75%) are GT3, the most commonly 
used regimen in India currently is SOF+DCV for 12 weeks with addition of RBV in 
cirrhotics. Hemogram and liver function tests are at 4-week intervals – additionally, if 
SOF+PR is selected, additional tests recommended when using interferon (e.g., thyroid 
stimulating hormone, alfa fetoprotein) are performed prior to initiation of therapy. HCV 
RNA quantification is also routinely performed at end of treatment (EOT) and if 
undetectable at EOT, an additional HCV RNA quantification is performed 12 weeks later 
to ascertain SVR status. The generic version of SOF/VEL was approved for use in India 
in May 2017.   
 
Monitoring of HCV Therapy in Thailand 
As of January 05, 2017, PR remains the standard of care (SOC) in national free-HCV 
treatment program. SOF and DCV have been registered in Thailand since October 2015 
but have been inaccessible because of the price. Approximately 700,000 Thais are 
suffering from chronic HCV infection of which HCV GT 3 is the most prevalent genotype 
(40-50%), followed by GT 1 (30-40%), and GT 6 (15-20%). Previous studies showed that 
about 70% of Thai HCV-infected participants had significant liver fibrosis and 30% of 
them met the definition for cirrhosis, especially in HIV-1 co-infected individuals, but were 
unable to receive HCV treatment due to financial constraints.   
 
Currently, there is no national guideline for monitoring HCV therapy in Thailand. Thai 
hepatologists usually treat chronic HCV based on the AASLD/IDSA guidelines. In 
Thailand, SOF and DCV are still expensive; therefore, HCV treatment is prioritized for 
patients who have an urgent medical need for HCV treatment. Diagnosis by the 
presence of HCV antibodies is followed by a non-invasive assessment of liver disease 
(FibroScan or APRI), to clarify whether the patient has an urgent need for HCV 
treatment. If APRI>1 or FibroScan>7.5KPa, HCV RNA quantification and HCV 
genotyping are performed. For 12 weeks of SOF+PR, CBC and blood chemistries are 
performed at 4-week intervals. Furthermore, additional safety laboratory tests such as 
thyroid-stimulating hormone are performed prior to initiation of therapy. For female 
patients, pregnancy testing is performed every 4 weeks until 6 months after completing 
the therapy. For interferon-free regimens (SOF+DCV for GT3 or LDV/SOF for GT 1 and 
GT 6), CBC and blood chemistry are done prior to treatment and at 12 weeks post-
treatment. For all regimens, a HCV RNA is performed on-treatment at week 4 and post-
treatment at week12 (SVR). 
 
Monitoring of HCV Therapy in the US 
As discussed above, HCV treatment guidance is provided by the AASLD/IDSA Panel 
and updated frequently on www.HCVguidelines.org. The US Panel recommends 
evaluation of the patients prior to and during HCV treatment with oral DAA regimens.  
Specifically, the US Panel recommends visits or telephone contact as clinically indicated 
during treatment to ensure medication adherence and to monitor for adverse events 
(AEs) and potential drug-drug interactions with newly prescribed medications. After 4 
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GFR, and hepatic function panel are recommended with additional testing as clinically 
indicated. Quantitative HCV viral load testing is recommended after 4 weeks of therapy 
and at 12 weeks following completion of therapy.  If HCV RNA is detectable at week 4 of 
treatment, repeat quantitative HCV RNA viral load testing is recommended after 2 
additional weeks of treatment (i.e., week 6). If quantitative HCV viral-load has increased 
by greater than 10-fold (>1 log10 IU/mL) on repeat testing at week 6 (or thereafter), then 
discontinuation of HCV treatment is recommended. In the US, the standard clinical 
practice is to evaluate patients taking HCV DAA therapy every 4 weeks during a typical 
12-week treatment course with office visits and laboratory testing. In addition, HCV DAA 
therapy is dispensed by commercial pharmacy and patients are required to interact with 
their pharmacy every 4 weeks during treatment, and HCV RNA monitoring after 4 weeks 
of treatment is often required to meet criteria for ongoing treatment. 
 
Sofosbuvir/velpatasvir (SOF/VEL): A Novel Pan-genotypic FDC Regimen 
SOF is an oral, nucleotide analogue inhibitor of HCV NS5B polymerase with 
demonstrated, potent antiviral activity in vitro and in vivo against HCV GT 1, 2, 3, 4, 5, 
and 6 (pan-genotypic) [13, 14, 15]. SOF was approved by the US Food and Drug 
Administration (FDA) in October 2013 and is widely available across the world, including 
as a generic agent manufactured in India which has the license to distribute SOF in 102 
countries. Velpatasvir (VEL) is an oral, second generation inhibitor of HCV NS5A with 
demonstrated potent antiviral activity in vitro and in vivo against HCV GT 1, 2, 3, 4, 5, 
and 6 (pan-genotypic). VEL was evaluated with SOF as a FDC tablet (SOF 400 mg/VEL 
100mg) taken by mouth once daily for 12 weeks in four clinical trials (ASTRAL-1, 2, 3, 
and 5), which included participants with HCV GT 1, 2, 3, 4, 5, and 6 with HIV-1 co-
infection (ASTRAL-5) [16] and among HCV mono-infection (ASTRAL 1, 2, 3) [17, 18] 
with and without compensated cirrhosis. The regimen evaluated was interferon- and 
RBV-free. Of note, ASTRAL-4 tested SOF/VEL in participants with decompensated 
cirrhosis (Child-Turcotte-Pugh classification B, [CTP B]); patients with CTP B or C are 
excluded from the present study [19]. Overall, the efficacy of SOF/VEL was high with 
SVR observed in 95-99% of participants (Table 2.1-3). In ASTRAL 1, 2, and 3, no HCV 
relapse was observed between the post-treatment week 12 (SVR) and post-treatment 
week 24 (SVR24), which is consistent with HCV eradication or cure. In the ASTRAL-1 
(HCV GT 1, 2, 4, 5, 6) study, SOF/VEL was compared to placebo tablets (delayed 
treatment group) in a double-blind manner. Importantly, no difference in safety and 
tolerability was observed between SOF/VEL and placebo, with respect to the quantity 
and quality of reported AEs and observed laboratory abnormalities. In the ASTRAL-2 
(HCV GT 2) and ASTRAL-3 (HCV GT 3) studies, SOF/VEL was compared to SOF + 
RBV in randomized controlled trials. SOF/VEL was superior to SOF + RBV with respect 
to SVR (efficacy) as well as safety and tolerability. In ASTRAL-5, two patients were 
incarcerated and hence did not have access to study drug while in prison, which resulted 
in failure to achieve SVR. In pooled analyses of data of participants from ASTRAL 1, 2 
and 3, the overall efficacy was estimated to 98%. Epclusa (fixed dose single tablet 
regimen of SOF/VEL) was approved by the US FDA on June 28, 2016. A marketing 
application for SOF/VEL has also been approved by the European Medicines Agency 
(EMA) on July 06, 2016. 
 


 
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As part of the ASTRAL trials, participants were subject to an intense followup, wherein 
clinic visits with or without laboratory testing, and adherence counseling were performed 
at baseline, weeks 2, 4, 6, 8, 10 and 12. Such an intense followup schedule is difficult to 
implement in the real world. However, it is encouraging that the monitoring practices 
currently followed as listed in Table 2.1-2 (above) for the delivery of other agents such 
as SOF/LDV in real-world cohorts, such as the HCV TARGET  [20] and TRIO [21] 
cohort, have resulted in SVR rates that are comparable to what were observed in the 
ION clinical trials of SOF/LDV. Therefore, it is likely that real-world SVR rates of 
SOF/VEL, with standard monitoring practices currently being used, will reflect what was 
observed in the ASTRAL trials. 
 
Table 2.1-3: SVR data from ASTRAL Trials  
 
 
SVR (95% confidence interval) 
 
ASTRAL-1 
ASTRAL-2 
ASTRAL-3 
ASTRAL-5* 
N 
624 
266 
552 
106 
Overall 
99.0 (98.0, 
>99.0) 
99.0 (96.0, 100) 
95.0 (92.0, 98.0) 
95.0 
Genotype 
 
 
 
 
  1a 
98.1 (95.2, 100) 
 
 
95.0 
  1b   
98.5 (96.5, 99.5) 
 
 
92.0 
  2 
100 (96.5, 100) 
99.0 (96.0, 100) 
 
100  
  3 
 
 
 
92.0 
  3a 
 
 
95.5 (90.9, 100) 
 
  3b 
 
 
100 (15.8, 100) 
 
  3h 
 
 
 
 
  3k 
 
 
100 (2.5, 100) 
 
  3 (no subtype  
confirmed) 
 
 
88.9 (51.8, 99.7) 
 
  4 
100 (96.9, 100) 
 
 
100  
  5 
97.2 (85.1, 99.9) 
 
 
 
  6 
100 (91.4, 100) 
 
 
 
Disease 
 
 
 
 
  No cirrhosis 
99.0 (97.7, 99.7) 
 
97.0 (93.5, 98.9) 
94.0 
  Cirrhosis 
99.2 (95.5, 100) 
 
91.3 (82.8, 96.4) 
100 
Prior Treatment 
 
 
 
 
  Naive 
98.8 (97.3, 99.7) 
 
97.1 (93.8, 98.9) 
93.0 
  Experienced 
99.5 (97.3, 99.6) 
 
90.1 (80.7, 95.9) 
97.0 
*All participants were HIV-infected 
 
Reinfection, Relapse, Cure 
Optimism for the eradication of HCV has been largely driven by the ability to cure HCV 
infection in a relatively short duration of time using agents that are safe and well 
tolerated. HCV cure, in the DAA era, is defined as the absence of HCV RNA in a 
quantitative PCR assay 12 weeks after the completion of treatment. However, it is 
important to note that HCV treatment induced cure is not associated with immunity to 
new HCV infection following exposure in the future. There are two important caveats that 
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small proportion of patients remain free of HCV at the end of treatment but exhibit HCV 
viremia at a time point thereafter (SVR or later)—this scenario could be attributable 
either to relapse or re-infection. HCV sequencing is required to distinguish one from the 
other. If the sequence of the virus observed is genetically identical to the sequence that 
was observed at baseline, the person is considered to have relapsed. However, if the 
sequence observed post SVR is unrelated to the sequence observed at baseline, the 
individual is considered to have been re-infected. In the pooled ASTRAL studies data 
which comprised participants from ASTRAL 1, 2, and 3 (n=1035), there were 12 
relapses and 1 reinfection [16, 17, 18, 19; see summary here- 
http://www.gilead.com/news/press-releases/2015/9/gilead-announces-svr12-rates-from-
four-phase-3-studies-evaluating-a-oncedaily-fixeddose-combination-of-sofosbuvir-sof-
and-velpatasvir-vel-gs5816-for-the-treatment-of-all-six-hepatitis-c-genotypes. In recent 
data presented from Australia and New Zealand [22, 23], re-infection was observed in 5 
out of 54 participants (Incidence of re-infection: 8.88 per 100 p-y) who had undetectable 
HCV RNA at EOT—active injection drug use was the strongest predictor of re-infection. 
Data on relapse and re-infection from settings in LMICs such as the study sites included 
in this study trial are lacking.  
 
Access to and Use of Mobile Phones and Text Messaging Among Non-US Sites 
Mobile phones and associated social media and messaging services are widely 
available in the participating countries. For example, in Brazil, WhatsApp is commonly 
used to contact participants and remind them of clinic visits. In India, text messaging 
services are used to remind participants of clinic visits. 
 
2.2 
Rationale 
 
The MINMON strategy that is being proposed to evaluate in this study includes the 
following components: 
 
a) No pre-treatment genotyping  
b) Entire treatment course (84 tablets) given to participant at baseline 
c) No scheduled on-treatment clinic visits 
d) No scheduled on-treatment monitoring 
e) Remote contact with participants at week 4 (adherence counseling and locator 
update) and week 22 (scheduling of SVR visit and locator update) 
 
The rationale for each of these components are listed below: 
 
No pre-treatment genotyping: The availability of pan-genotypic HCV treatment regimens 
preclude the need for HCV genotyping. Prior to SOF/DAC and SOF/VEL, genotyping 
was used to select treatment regimen and/or treatment duration. However, SOF/VEL 
has demonstrated high levels of efficacy across genotypes 1-6 and is approved by the 
US FDA for management of HCV disease in GT 1, 2, 3, 4, 5 or 6. The generic version of 
the fixed dose single-tablet regimen of SOF/VEL was recently approved for production 
by Indian generic manufactures for use in India and in 102 additional countries. 
SOF/VEL is also being utilized as the primary treatment regimen in at least two countries 
with ongoing robust HCV elimination programs, Iceland and Georgia. 


 
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Entire treatment course (84 tablets) given to participant at baseline and no on-treatment 
planned clinic visits: Most HCV treatment programs require patients to come in for refills 
on a 4-weekly basis and in some cases, every 2 weeks (e.g., Chennai, India). These 
visits could take considerable amount of time when accounting for travel and waiting 
time at the facility resulting in loss of wages. In the US, ensuring insurance papers are in 
place poses an additional burden to the patient. During these visits, patients are 
essentially provided with the next 2- or 4-week supply, a physician consult and a lab 
draw for HCV RNA monitoring and/or safety labs. Given the safety and efficacy profile of 
SOF/VEL, it is possible that providing patients with the entire 12-week supply of HCV 
treatment at initiation and not requiring any in-person follow-up could result in similar 
SVR rates as observed in the ASTRAL trials or real-world HCV cohorts such as 
TARGET and TRIO. Many HIV clinics globally provide ART for 3-6 month periods and 
viral suppression rates appear to be comparable to programs requiring participants to 
come in more frequently. More importantly, reducing the number of on-treatment clinic 
visits could minimize lost wages and dramatically decrease costs even in countries such 
as the US where manpower (physician/nurse/pharmacist) costs are significantly higher 
than in other settings. Further, the reduction in the number of clinic visits could 
potentially allow the clinic to deliver care to more patients with the same manpower. The 
provision of the entire 12-week supply at initiation could also improve adherence and 
consequently, outcomes in populations who are at risk for HCV infection and travel 
frequently (e.g., truck drivers). 
 
No scheduled on-treatment monitoring: In the ASTRAL-1 trial the safety profile of 
SOF/VEL was comparable to that of the placebo arm—this raises the question of the 
necessity of on-treatment safety monitoring in a large majority of the patients. Further, 
given the relatively short treatment duration (12 weeks) and absence of stopping rules 
for futility, the role of on-treatment HCV RNA monitoring is also debatable. HCV RNA 
testing is currently recommended and usually ordered at on-treatment week 4 and EOT 
(in some settings) to assess adherence and to detect on-therapy virologic breakthrough. 
Virologic breakthrough is rare with SOF/VEL and has been generally linked to very poor 
adherence. In a pooled analysis of data from the ASTRAL trials on-treatment HCV RNA 
was not shown to be predictive of treatment response. Therefore, it is highly unlikely that 
the HCV treatment course would be modified by the results of on-treatment RNA 
quantification. This is an important issue in LMIC settings where access to HCV RNA 
quantification is limited (and expensive where available) and the reduction in the number 
of these tests from treatment protocols is expected to greatly improve access. Therefore, 
the study team proposes no planned on-treatment safety or HCV RNA monitoring. Of 
importance, participants with decompensated cirrhosis and chronic HBV infection 
(HBsAg positive) will be excluded from the study as these participants will not be eligible 
for a MINMON strategy; it is equally important to note that these groups probably 
account for <20% of persons chronically-infected with HCV globally.  
 
Remote contact with participants at week 4 (adherence counseling and locator update) 
and week 22 (scheduling of SVR visit and locator update): In the real world, programs 
are measured by their success in objectively quantifiable outcomes. For example, in 
HIV, viral suppression is the gold standard to assess program effectiveness. Similarly, 
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treatment programs. There are two critical components to achieving SVR: (1) Treatment 
persistence (taking an adequate duration of therapy) and adherence (taking daily 
SOF/VEL); and (2) confirmation of HCV eradication (SVR) at least 12 weeks after 
completing treatment. In the US, approximately 20% of patients who complete treatment 
do not return for SVR assessment in a timely manner. In global HCV programs, such as 
the free HCV program in Punjab, India, program staff are currently facing challenges 
bringing patients back in for the SVR assessment visit and are using different strategies 
to track patients.  
 
According to the AASLD/IDSA guidelines [5, 9], the recommended approach to 
encourage treatment persistence/adherence and confirmation of SVR is pharmacist 
and/or clinicians contact with participants every 4 weeks and in most non-US settings, 
HCV treatment programs and treating clinicians require patients to come in for refills or 
safety labs at least once every 4 weeks, if not more frequently. Therefore, this study will 
leverage existing technology to conduct remote contacts with participants at two time 
points during the course of treatment and assessment of SVR. The remote contact will 
also be associated with minimal costs, which we will capture and factor into the cost 
analysis. 
 
It is anticipated that these remote contacts will last less than 5 minutes and therefore, do 
not foresee this as burdensome on the staff as several programs already use similar 
approaches to track participants. The week 4 contact is not designed to be an intensive 
adherence intervention, rather a quick adherence check, clarification of the regimen, and 
re-enforcement of the importance of adherence early in the course of treatment. Despite 
detailed instructions at the time of clinical encounters, many participants may leave 
unsure of medical instructions. Therefore, the week 4 remote contact is in keeping with 
good clinical practice and will optimize outcomes in the subset of participants who may 
have misunderstood or have questions or concerns about the study medication. 
Responses will be standardized based on reasons for non-adherence: e.g., forgot, side 
effects, chose not to take, lost study medication, or decided to stop. Standardizing 
responses will ensure that participants receive the same type of support regardless of 
the mechanism used (i.e., phone, text, WhatsApp, etc.) This simple and inexpensive 
remote contact will also be helpful in assessing the success of the MINMON approach 
both in the trial and in the real world, as it may be possible for programs to estimate 
outcomes of participants who do not return for SVR assessment using week 4 
adherence data. Given the advances in technology and widespread adaptation of newer 
informatics, remote participant contact could be pre-programmed to provide support and 
collect information at specific intervals, and the study team believes that these newer 
forms of remote contact will be increasingly used in medicine. 
 
An additional incentive for attending the SVR visit will be included in this clinical trial. The 
rationale is to minimize lost-to-follow-up (LTFU) and measure SVR in as many 
participants as possible to validate the MINMON strategy. Any participant who does not 
return for the SVR visit will be considered a failure even if the true outcome was HCV 
cure with SOF/VEL. In light of the importance of determining the SVR outcome of the  


 
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MINMON study for the applicability of this strategy outside the trial setting, this additional 
measure, an incentive for attending the SVR assessment, is intended to minimize 
missed SVR visits. We will incorporate the value of this incentive into the cost-analysis.  
 
If the monitoring protocol that is being proposed is found to be efficacious and 
comparable to what is currently being observed in clinical settings globally, it would imply 
that the HCV-infected persons, for the large part, could be treated from settings with 
minimal infrastructure. In fact, HCV care could be rolled out of primary health care 
centers where routine blood work is available—at baseline, one would need to perform a 
complete blood panel, hepatic function panel and a renal panel to stage liver disease. 
Point-of-care HCV antibody tests are already available. If the individual is a 
decompensated cirrhotic, he/she could be referred to a tertiary care center. If not, 
treatment could be initiated following HCV RNA quantification. The availability of the 
GeneXpert cartridges for quantification of HCV RNA [24] has the potential to transform 
any center with electricity and an individual with high-school level of education to 
perform HCV RNA quantification. There are approximately four to five times the number 
of people living with HCV globally compared to HIV—to ensure that treatment reaches 
them all and to truly have a shot at eradication of HCV, it is critical to improve access 
while reducing cost and associated treatment complexities.    
 
However, what is being proposed is novel but high-risk and has never been piloted for 
the delivery of HCV care. It is possible that adherence and treatment completion rates, if 
the entire treatment supply is provided upfront with no health care contact thereafter for 
the remainder of the treatment duration, could be inferior to the SOC. This single-arm 
study, open to US and non-US sites, will enroll 400 participants, all of whom will be 
followed using the MINMON protocol only. The rationale for limiting enrollment of HIV-
coinfected participants to <50% is to ensure the findings of this trial are generalizable to 
all HCV infected persons. Given that this trial will be recruiting from ACTG sites that are 
primarily HIV clinics, it is highly possible that there may be an overrepresentation of HIV-
infected persons.  
 
The rationale for limiting enrollment of cirrhotics to <20% is also to ensure that the 
sample is representative of all HCV-infected persons globally. Since this study seeks to 
evaluate a low-cost treatment delivery strategy aimed at promoting the elimination 
agenda, the primary target population will be the >90% of the HCV-infected persons who 
are unaware of their status—it is likely the >80% of these individuals will be non-cirrhotic. 
Cirrhotic individuals are more likely to engage in care with more frequent clinic visits and 
consequently, more likely to be recruited into the study. 
 
Further, the findings from this study will inform the need for a future randomized clinical 
trial (RCT) that will compare the MINMON approach versus SOC. If the findings from this 
trial conclusively indicate that the MINMON approach achieves high SVR (>96%) that is 
comparable to what is observed in routine clinical settings, a RCT will not be needed as 
a high benchmark for SVR will be met. Conversely, if findings from this study 
conclusively indicate that the MINMON approach is inferior (evidence than SVR is 
<95%), an RCT will not be needed as a low benchmark for SVR will have been met and 
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neither a high nor low benchmarks is met (ie, observed SVR 93-97%), this study will 
inform the design and sample size of a potential future RCT comparing the MINMON 
approach to SOC. 
 
Plan for Enrollment of Subpopulations 
There are no exclusion criteria related to gender or race. The FDC of SOF/VEL was not 
associated with adverse developmental outcomes in animal studies. However, this 
combination has not been studied extensively in pregnant women [EPCLUSA package 
insert, 2016]. Therefore, we will exclude pregnant women and women of reproductive 
potential who are unwilling to use contraceptives while on study treatment.  
 
3.0 
STUDY DESIGN 
 
This study will enroll 400 participants who will be followed using a MINMON protocol for 
a duration of 24 weeks in order to obtain primary outcome information regarding SVR 
status, as well as additional information for secondary objectives over the longer 
duration of 72 weeks. The MINMON strategy is comprised of: 1) minimal pre-treatment 
assessment including confirmation of viremia by HCV RNA and liver disease staging 
using routine clinical exam and non-invasive parameters (ALT, AST, and platelet count 
[and bilirubin, albumin, and INR in persons with evidence of cirrhosis by FIB-4]) and no 
genotyping; 2) distribution of complete HCV treatment course at study initiation (i.e., 84 
days of SOF/VEL); 3) no planned on-treatment laboratory monitoring; 4) no planned 
clinic or pharmacy visits prior to SVR evaluation; and 5) remote contact at treatment 
week 4 and post-treatment at week 22 to update locator information and to facilitate 
attendance at the SVR evaluation visit (weeks 22 to 28). The week 4 remote contact will 
include adherence assessment and reinforcement which is also considered to be a part 
of the MINMON strategy.  
 
All participants will be treatment-naïve, with active HCV-infection, with or without HIV-1 
co-infection, and if cirrhotic, will be classified as compensated cirrhotics based on CTP 
score. All participants will receive study-provided treatment (FDC of SOF/VEL) for a 
duration of 12 weeks followed by evaluation 12 weeks later to ascertain SVR status. 
Upon SVR evaluation, all participants will enter Step 2 of the study and will be followed 
for an additional 48 weeks to examine liver disease regression post-SVR, measure the 
incidence of HCV re-infection, and other non-primary outcomes. Measures of disease 
regression after cure are important to understanding future disease burden and cost 
associated with liver disease. Reinfection rates are critically important for both public 
health planning and advocacy purposes when seeking to expand the availability of HCV 
treatments. In addition, cost-benefit analyses will be conducted using cost data and 
outcomes gathered from this study. 
 
At entry (Step 1), all participants will receive the entire study-provided treatment supply, 
following study entry procedures, with the first dose being observed by study staff. The 
next planned study visit is the key primary outcome evaluation for SVR, scheduled at 
week 24. There will be no planned interim in-person study visits with participants 
between entry and week 24. Detailed locator information will be collected at entry (see 
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the primary outcome evaluation at the week 24 visit, sites will contact participants at 
weeks 4 and 22, via a remote mechanism based upon the participant’s choice and 
availability, in order to assess adherence status at week 4 and to schedule the SVR 
evaluation visit at week 24, as well as update the locator information. At week 4, the 
participant will be asked if he/she is taking the study medication and about adherence, 
changes in contact information, and reminders for the study visit for SVR evaluation. If 
participants report sub-optimal adherence or that they are not taking their HCV 
medication, they will be read (if a phone contact) or message (if remote contact is via 
email/text message/WhatsApp) a standard script highlighting the benefits of HCV 
therapy and the importance of adherence. They will also be asked about reasons for 
their non-adherence and then receive standardized encouragement and clarification 
about the medication and importance of adherence. There will be no further site-initiated 
interaction with the participant until week 22, at which time participants will be queried 
about any changes to their contact information and will also be reminded of their 
upcoming SVR visit. These contacts are designed to help keep participants engaged 
with the study and keep their contact information up to date in order to minimize LTFU 
prior to the primary outcome- evaluation of SVR. Resource utilization, including staff time 
(both for remote contact as well as unplanned study visits) and any associated 
laboratory or other tests ordered during unplanned clinic visits (e.g., Magnetic 
Resonance Imaging [MRI], ultrasonogram, blood tests) will be documented, translated to 
costs using reimbursement rates from WHO CHOICE and the U.S. Center For Medicare 
and Medicaid Services, and incorporated into the cost analysis.   
 
Following the SVR evaluation visit, which is expected to be at week 24, all participants 
will enter Step 2 for two additional scheduled post-SVR evaluation study visits at weeks 
48 and 72. At each of these Step 2 study visits, a blood sample will be drawn and liver 
disease will be staged in all participants using FIB-4 (and calculated CTP if cirrhotic), 
and where available, liver elastography, in addition to the Model for End-Stage Liver 
Disease (MELD) score. Participants who have SVR evaluation after week 24 will enter 
Step 2 at the time of SVR evaluation and the schedule of an additional post-SVR 
evaluation visits will be dependent on the week of Step 2 entry. Step 2 will end at week 
72, from the time of study entry, independent of the time of Step 2 entry (for example, a 
participant who undergoes SVR evaluation at week 60 will have one remote contact visit 
at week 68 and a final visit at week 72). 
 
4.0 
SELECTION AND ENROLLMENT OF PARTICIPANTS 
 
4.1 
Inclusion Criteria (Step 1) 
 
4.1.1 Ability and willingness of participant to provide informed consent. 
 
4.1.2 Men and women age ≥18 years. 
 
4.1.3 Active HCV infection confirmed by a detectable HCV RNA by PCR (HCV RNA 
>1000 international units (IU)/ml) within 35 days prior to study entry. HCV RNA 
must be obtained by any FDA-approved test for quantifying HCV RNA at any 
local laboratory that has a CLIA certification, its equivalent, or at any network-


 
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approved non-US laboratory that operates in accordance with Good Clinical 
Laboratory Practices (GCLP) and participates in appropriate external quality 
assurance programs. 
     
NOTE: HCV RNA can be obtained at screening visit (refer to section 6.3.13).   
 
4.1.4 HCV treatment naïve defined as not having been previously treated for HCV 
infection with any medications approved for the treatment of HCV in any country.  
 
4.1.5 Liver disease stage defined as non-cirrhotic or compensated cirrhotic 
(metric/diagnostic criteria used for fibrosis staging) within 35 days prior to study 
entry as listed below: 
 
A. FIB-4 <3.25 corresponding to no cirrhosis  
 
OR 
 
B. FIB-4 ≥3.25 AND Child-Turcotte-Pugh (CTP) Score ≤6 indicating CTP Class 
A corresponding to compensated cirrhotic. 
 
NOTE: Please refer to the A5360 PSWP for the website link to calculate the 
FIB-4 and CTP scores.  
 
4.1.6 HIV-1 infection status documented as either absent or present, as defined below: 
 
Absence of HIV-1 infection, as documented by any licensed rapid HIV test or 
HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, within 60 
days prior to entry. 
 
OR 
 
HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test 
kit at any time prior to entry and confirmed by a licensed Western blot or a 
second antibody test by a method other than the initial rapid HIV and/or E/CIA, or 
by HIV-1 antigen or plasma HIV-1 RNA viral load.  
 
NOTE: The term "licensed" refers to a US FDA-approved kit, which is 
recommended. For sites that are unable to obtain an FDA-approved kit, a kit that 
has been certified or licensed by an oversight body within the country and 
validated internally is acceptable.  
 
WHO and CDC (US Centers for Disease Control and Prevention) guidelines 
mandate that confirmation of the initial test result must use a test that is different 
from the one used for the initial assessment. A reactive initial rapid test should be 
confirmed by either another type of rapid assay or an E/CIA that is based on a 
different antigen preparation and/or different test principle (e.g., indirect versus 
competitive), or a Western blot or a plasma HIV-1 RNA viral load. 


 
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4.1.7 For HIV co-infected participants, HIV-1 RNA obtained within 90 days prior to 
study entry by any US laboratory that has a CLIA certification or its equivalent, or 
at any network-approved non-US laboratory that operates in accordance with 
Good Clinical Laboratory Practices (GCLP) and participates in appropriate 
external quality assurance programs. 
 
4.1.8 For HIV co-infected participants, CD4+ cell count obtained within 90 days prior to 
study entry at any US laboratory that has a CLIA certification or its equivalent, or 
at any network-approved non-US laboratory that operates in accordance with 
Good Clinical Laboratory Practices (GCLP) and participates in appropriate 
external quality assurance programs. 
 
4.1.9 HIV co-infected participants must satisfy one of the two criteria listed below: 
 
A. If a participant is HIV-infected and is taking ART then, plasma HIV RNA <400 
copies/mL based on criteria listed in section 4.1.7 AND current ARV regimen 
does not include efavirenz (EFV) AND no exposure to EFV ≤14 days prior to 
study entry. Any absolute CD4+ count is acceptable if this HIV RNA criterion 
is met. 
 
NOTE: Any participant on an EFV containing ART regimen during the 
screening period must be switched off EFV and have another regimen, 
excluding EFV, started at least 14 days prior to study entry. 
 
OR  
 
B.  If a participant is HIV-infected AND not taking ART, absolute CD4+ count 
must be >350 cells/µl based on criteria listed in section 4.1.8. 
 
4.1.10 The following laboratory values obtained within 35 days prior to entry by any US 
laboratory that has a CLIA certification or its equivalent, or at any network-
approved non-US laboratory that operates in accordance with Good Clinical 
Laboratory Practices (GCLP) and participates in appropriate external quality 
assurance programs. 
• 
Albumin >3.0 g/L 
• 
Hemoglobin >8.0 g/dL for women; >9.0 g/dL for men 
• 
Platelet count >50,000/mm3 
• 
Calculated creatinine clearance (CrCl) using Cockcroft-Gault method  >30 
mL/min   
• 
Aspartate aminotransferase (AST/SGOT) <10 times the upper limit of the 
normal range (ULN) 
• 
Alanine aminotransferase (ALT/SGPT) <10 times the ULN 
• 
Total bilirubin <1.5 times the ULN for participants not on atazanavir (ATV) 
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• 
International normalized ratio (INR) <1.5 times the ULN  
 
NOTE: Please refer to the A5360 PSWP for the website link to calculate CrCl 
using the Cockcroft-Gault calculator. 
 
4.1.11 Female participants of reproductive potential (defined as women who have not 
been post-menopausal for at least 24 consecutive months, i.e., who have had 
menses within the preceding 24 months, or women who have not undergone 
surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or 
bilateral salpingectomy) must have a negative serum or urine pregnancy test 
within 48 hours prior to study entry by any laboratory or clinic that has a CLIA 
certificate or its equivalent, or is using a point-of-care (POC)/CLIA-waived test. 
The serum, urine or POC pregnancy test must have a sensitivity of at least 25 
mIU/mL. 
 
4.1.12 All participants of reproductive potential must agree not to participate in a 
conception process (e.g., active attempt to become pregnant or to impregnate, 
sperm donate, in vitro fertilization,) while on study treatment and for 6 weeks 
after stopping protocol-specified medication.  
 
4.1.13 When participating in sexual activity that could lead to pregnancy, all participants 
of reproductive potential must agree to use at least one reliable form of 
contraceptive while receiving protocol-specified medication, and for 6 weeks after 
stopping the medication. Such methods include: 
• 
Condoms (either self or require their partner to use one) with or without a 
spermicidal agent  
• 
Diaphragm or cervical cap with or without spermicidal agent 
• 
Intrauterine device (IUD) 
• 
Hormone-based contraceptive 
• 
Tubal ligation 
 
NOTE: Providers and participants should be advised that not all contraceptive 
choices listed above can prevent HIV transmission and that some may actually 
increase the risk of HIV acquisition. Study participants who are sexually active 
with HIV-1 negative or unknown HIV-1 serostatus partners should be advised 
that they need to consider effective strategies for reducing the risk of HIV 
transmission, as well as meeting the requirement for effective contraception 
during their participation in the study. Study participants should discuss 
contraceptive choices and HIV risk reduction methods with their health care 
provider. 
 
4.1.14  Participants who are not of reproductive potential (women who have been post-
menopausal for at least 24 consecutive months or have undergone hysterectomy 
and/or bilateral oophorectomy or salpingectomy or men who have documented 
azoospermia or undergone vasectomy) are eligible without requiring the use of 
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specified below. Male participants do not need to provide information on their 
female partner’s reproductive potential. 
 
Written or oral documentation communicated by clinician or clinician’s staff of 
one of the following: 
• 
Physician report/letter 
• 
Operative report or other source documentation in the patient record (a 
laboratory report of azoospermia is required to document successful 
vasectomy)  
• 
Discharge summary 
• 
Follicle stimulating hormone-release factor (FSH) measurement elevated into 
the menopausal range as established by the reporting laboratory. 
 
4.1.15 Life expectancy >12 months, in the opinion of the site investigator.   
 
4.1.16 Willingness and ability to be contacted remotely via telephone, text message, 
email, social media applications or any other modality. 
 
4.2 
Exclusion Criteria (Step 1) 
 
4.2.1 Positive for the presence of hepatitis B virus (HBV) surface antigen (HBsAg).  
 
4.2.2 For cirrhotic participants, CTP score >6 corresponding to Class B or C (Please 
refer to the A5360 PSWP for the website link to calculate the CTP score). 
 
4.2.3 Breastfeeding or pregnancy. 
 
4.2.4 Known allergy/sensitivity or any hypersensitivity to components of study drug(s) 
or their formulation. 
 
4.2.5 Active drug or alcohol use or dependence and other conditions that, in the 
opinion of the site investigator, would interfere with adherence to study 
requirements. 
 
4.2.6 Acute or serious illness requiring systemic treatment and/or hospitalization within 
35 days prior to study entry. 
 
4.2.7 In HIV positive participants, presence of active or acute AIDS-defining 
opportunistic infections within 35 days prior to study entry.  
 
NOTE: AIDS-defining opportunistic infections as defined by the CDC found in the 
following document: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm 
 
4.2.8 Any history of hepatic decompensation including ascites, spontaneous bacterial 
peritonitis, hepatic encephalopathy, hepatorenal syndrome, and/or bleeding 
esophageal varices prior to study entry. 


 
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4.2.9 Use of prohibited medications within the past 14 days prior to study entry (please 
refer to the A5360 PSWP for the list of prohibited medications). 
 
NOTE: ART regimens must not contain prohibited medications (please refer to 
the A5360 PSWP for the list of prohibited medications). 
 
4.3 
Inclusion Criteria (Step 2) 
 
4.3.1 Completion of SVR evaluation visit in Step 1. 
 
4.4 
Exclusion Criteria (Step 2) 
 
There are no exclusion criteria for Step 2. 
 
4.5 
Study Enrollment Procedures 
 
4.5.1 Prior to implementation of this protocol, and any subsequent full-version 
amendments, each site must have the protocol and the protocol consent form(s) 
approved, as appropriate, by their local institutional review board (IRB)/ethics 
committee (EC) and any other applicable regulatory entity (RE). Upon receiving 
final approval, sites will submit all required protocol registration documents to the 
DAIDS Protocol Registration Office (DAIDS PRO) at the Regulatory Support 
Center (RSC). The DAIDS PRO will review the submitted protocol registration 
packet to ensure that all of the required documents have been received.  
 
Site-specific informed consent forms (ICFs) WILL be reviewed and approved by 
the DAIDS PRO, and sites will receive an Initial Registration Notification from the 
DAIDS PRO that indicates successful completion of the protocol registration 
process. A copy of the Initial Registration Notification should be retained in the 
site’s regulatory files. 
 
Upon receiving final IRB/EC and any other applicable RE approval(s) for the 
amendment, sites should implement the amendment immediately. Sites are 
required to submit an amendment registration packet to the DAIDS PRO at the 
RSC. Site-specific ICF(s) WILL be reviewed and approved by the DAIDS PRO, 
and sites will receive an Amendment Registration Notification from the DAIDS 
PRO that approves the site-specific ICFs and indicates successful completion of 
the amendment protocol registration process. A copy of the final Amendment 
Registration Notification issued by the DAIDS PRO should be retained in the 
site’s regulatory files. 
 
For additional information on the protocol registration process and specific 
documents required for initial and amendment registrations, refer to the current 
version of the DAIDS Protocol Registration Manual.  
 


 
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Once a candidate for study entry has been identified, details will be carefully 
discussed with the participant. The participant will be asked to read and sign the 
approved protocol consent form.  
 
For participants from whom a signed informed consent has been obtained, an 
ACTG Screening Checklist must be entered through the Data Management 
Center (DMC) Participant Enrollment System.  
 
4.5.2 Protocol Activation 
 
Prior to enrollment, sites must complete the Protocol Activation Checklist found 
on the ACTG Member website. This checklist must be approved prior to any 
screening of participants for enrollment.  
 
4.5.3 Participant Registration 
 
For participants from whom informed consent has been obtained, but who are 
deemed ineligible or who do not enroll into the initial protocol step, an ACTG 
Screening Failure Results form must be keyed into the database.  
 
Participants who meet the enrollment criteria will be registered to the study 
according to standard ACTG DMC procedures.  
 
4.6 
Co-enrollment Guidelines  
 
US sites are encouraged to co-enroll participants in A5128, “Plan for Obtaining Informed 
Consent to Use Stored Human Biological Materials (HBM) for Currently Unspecified 
Analyses.” Co-enrollment in A5128 does not require permission from the A5360 protocol 
chairs.  
 
Non-US sites are encouraged to co-enroll participants in A5243, “Plan for Obtaining 
Human Biological Samples at Non-U.S. Clinical Research Sites for Currently 
Unspecified Genetic Analyses.” Co-enrollment in A5243 does not require permission 
from the A5360 protocol chairs.  
 
For specific questions and approval for co-enrollment in other studies, sites should first 
check the PSWP or contact the protocol team via email as described in the Study 
Management section. 
 
If there are concerns about exceeding volume limits for blood draws, please note that 
A5128 and A5243 allow participants to consent to the study without allowing a blood 
sample to be collected. In these cases, if a future study wants to evaluate a participant’s 
DNA sometime later, sites would be able to access a stored aliquot from the initial study 
(if there are any available). It is also possible for a participant to enroll into A5128 or 
A5243 and postpone the required blood draw until a later time. For more input, contact 
the A5128 or A5243 teams. 
 


 
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5.0 
STUDY TREATMENT  
 
Study treatment is defined as the once-daily oral FDC sofosbuvir/velpatasvir (SOF/VEL 
[Tradename: Epclusa]) containing 400 mg of SOF and 100mg of VEL. If a participant is 
co-infected with HIV, HIV medications will NOT be provided as part of this study.   
 
5.1 
Regimens, Administration, and Duration 
 
5.1.1 Regimens 
 
Participants will receive FDC SOF/VEL (400mg/100mg) orally once daily with or 
without food. 
 
5.1.2 Administration and Duration 
 
Participants will take SOF/VEL orally once daily with or without food and will 
receive treatment for a duration of 12 weeks. Study staff will observe the first 
dose being taken by the participant upon completion of all entry evaluations. 
Participants should be instructed to open and finish one bottle of study product at 
a time. When the participant takes the last pill of SOF/VEL from each bottle, 
he/she will be instructed to contact the site to report the completion of the bottle. 
Participants will, therefore, contact a site a maximum of three times to indicate 
completion of a bottle. See A5360 MOPS for additional information on reporting 
of treatment stop date. 
 
In the scenario of lost study medication, the participant will be asked to contact 
the study site as soon as possible. If the participant has been off study 
medication less than 2 weeks (≤14 days), he/she will be eligible for a one-time 
replacement of study medication to complete the 12 week course. Participants 
who report a subsequent loss of study medication will not be eligible for 
replacement and will enter the follow-up phase (week 24 visit). If the participant 
has not taken study medication for more than 2 weeks (≥15 days), study 
medication will not be replaced and the participant will enter the follow-up phase 
(week 24 visit). 
 
5.2 
Study Product Formulation and Preparation 
 
5.2.1 Sofosbuvir/Velpatasvir manufactured by Gilead Sciences, Inc., will be supplied 
as 400/100 mg film-coated tablets for oral administration. Store below 30°C 
(86ºF). Dispense only in original container. 
 


 
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5.3 
Pharmacy: Product Supply, Distribution, and Accountability 
 
5.3.1 Study Product Acquisition/Distribution 
 
The FDC of SOF/VEL will be provided by Gilead Sciences, Inc. and will be 
available through the NIAID Clinical Research Products Management Center 
(CRPMC). The site pharmacist should obtain the study product(s) for this 
protocol by following the instructions in the manual Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks.  
 
Any study product not provided by the study must comply with the NIAID 
(DAIDS) policy that outlines the process for authorizing the use of study products 
not marketed in the US in NIAID (DAIDS)-supported and/or – sponsored clinical 
trials. This policy is available on the NIAID (DAIDS) website at: 
https://www.niaid.nih.gov/sites/default/files/NonFDAapprovedProducts.pdf. 
 
5.3.2 Study Product Accountability 
 
The site pharmacist is required to maintain complete records of all study products 
received from the NIAID CRPMC and subsequently dispensed. At US CRSs, all 
unused study products must be returned to the NIAID CRPMC (or as otherwise 
directed by the sponsor) after the study is completed or terminated. The 
procedures to be followed are provided in the manual Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks. At non-US CRSs, the site 
pharmacist must follow the instructions in the Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks for the destruction of unused 
study products. 
 
5.4 
Concomitant Medications 
 
Whenever a concomitant medication or study agent is initiated or a dose changed, 
investigators must review the concomitant medication’s and study agent’s most recent 
package insert, Investigator’s Brochure, or updated information from DAIDS to obtain the 
most current information on drug interactions, contraindications, and precautions. 
 
Additional drug information may be found on the ACTG Precautionary and Prohibited 
Medications Database located at: http://tprc.pharm.buffalo.edu/home/di_search/. 
 
5.4.1 Prohibited Medications 
 
Please refer to the A5360 PSWP for the list of prohibited medications.  
 
5.4.2 Precautionary Medications 
 
Please refer to the A5360 PSWP for the list of precautionary medications.  
 


 
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6.0 
CLINICAL AND LABORATORY EVALUATIONS 
 
6.1 
Schedule of Evaluations 
 
6.1-1: Schedule of Evaluations: Step 1- Visits up Until SVR Evaluation 
 
Evaluation 
Screening 
Entry/Week 
0 
Weeks 
SVR Evaluation 
Visit (if week 24 
visit is missed; 
can occur up to 
week 72) 
Unplanned Study 
Visits (see 
section 6.2.6) 
4 
22 
24 
Window +7 days 
Window -14/+28 
days 
Documentation of Active HCV 
Infection 
X 
 
 
 
 
 
 
Documentation of HIV-1 Status 
X 
 
 
 
 
 
 
Calculated FIB-4 Score 
X 
 
 
 
X 
X 
As needed. 
MELD Score 
 
X 
 
 
 
 
 
Documentation of Cirrhosis Status 
X 
 
 
 
X 
X 
As needed. 
Calculated CTP Score  (if cirrhotic 
by FIB-4) 
X 
 
 
 
X 
X 
Liver Elastography (see section 
6.3.7) 
 
X 
 
 
X 
X 
 
Medical History 
X 
X 
 
 
 
 
 
Medication History 
X 
X 
 
 
 
 
 
Clinical Assessments  
X 
X 
 
 
X 
X 
As needed. 
Hematology 
X 
X 
 
 
X 
X 
Liver Function Tests 
X 
X 
 
 
X 
X 
Blood Chemistries  
X 
X 
 
 
X 
X 
As needed. 


 
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Evaluation 
Screening 
Entry/Week 
0 
Weeks 
SVR Evaluation 
Visit (if week 24 
visit is missed; 
can occur up to 
week 72) 
Unplanned Study 
Visits (see 
section 6.2.6) 
4 
22 
24 
Window +7 days 
Window -14/+28 
days 
Calculated Creatinine Clearance 
X 
 
 
 
 
 
 
INR 
X 
 
 
 
X 
X 
As needed. 
Pregnancy Testing 
X 
X 
 
 
If pregnancy is suspected. 
HBV Panel 
X 
 
 
 
 
 
 
CD4+ (if HIV+) 
X 
 
 
 
X 
X 
 
Plasma HIV-1 RNA (if HIV+) 
X 
 
 
 
X 
X 
 
 
Plasma HCV RNA 
X 
 
 
 
X 
X 
 
Stored Plasma/PBMC/Serum 
 
X 
 
 
X 
X 
As needed. 
(Plasma sample 
will be stored if 
blood sample 
obtained.) 
Adherence Assessment 
 
 
X (via 
remote 
contact) 
 
X 
X 
 
Health Outcomes Questionnaire 
 
X 
 
 
X 
X 
X 
Health Care Utilization 
Questionnaire 
 
X 
 
 
X 
X 
X 
Substance Use Questionnaire 
 
X 
 
 
X 
X 
 


 
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Evaluation 
Screening 
Entry/Week 
0 
Weeks 
SVR Evaluation 
Visit (if week 24 
visit is missed; 
can occur up to 
week 72) 
Unplanned Study 
Visits (see 
section 6.2.6) 
4 
22 
24 
Window +7 days 
Window -14/+28 
days 
HCV Therapy Dispensed/First Dose 
Observed 
 
X 
 
 
 
 
 
Adherence Education and 
Counseling 
 
X 
 
 
 
 
 
Pregnancy Prevention Counseling 
X 
X 
 
 
 
 
 
Cirrhosis Counseling 
 
X 
 
 
X 
X 
 
HCV Risk-reduction Counseling 
 
X 
 
 
X 
X 
 
Locator Information 
 
X 
Update information, if 
needed. 
 
 
 
Remote Contact with Participants 
Outside of Planned Clinic Visits  
 
 
X 
X (see note 
in section 
6.2.4) 
 
 
 
 
 
 


 
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6.1-2: Schedule of Evaluations: Step 2- Visits Post SVR Evaluation  
 
Evaluation 
Weeks 
42 
48 
68 
72 
Window +28 days 
Calculated FIB-4 Score 
 
X 
 
X 
MELD Score 
 
X 
 
X 
Calculated CTP Score  (if cirrhotic by FIB-4) 
 
X 
 
X 
Liver Elastography (see section 6.3.7) 
 
X 
 
X 
Clinical Assessments  
 
X 
 
X 
Hematology 
 
X 
 
X 
Liver Function Tests 
 
X 
 
X 
Blood Chemistries  
 
X 
 
X 
Calculated Creatinine Clearance 
 
X 
 
X 
INR 
 
X 
 
X 
Plasma HCV RNA (if SVR responder) 
 
X 
 
X 
Stored Plasma/PBMC/Serum 
 
X 
 
X 
Health Outcomes Questionnaire 
 
X 
 
X 
Health Care Utilization Questionnaire 
 
X 
 
X 
Substance Use Questionnaire 
 
X 
 
X 
Cirrhosis Counseling 
 
X 
 
X 
HCV Risk-reduction Counseling 
 
X 
 
X 
Remote Contact with Participants Outside of Planned Clinic 
Visits 
X 
 
X 
 
 


 
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6.2 
Timing of Evaluations 
 
6.2.1 Screening Evaluations  
 
Screening evaluations must occur prior to the participant starting any study 
medications, treatments, or interventions. 
 
Screening evaluations to determine eligibility must be completed within 35 days 
prior to study entry unless otherwise specified in section 4.0. 
 
In addition to data being collected on participants who enroll into the study, 
demographic, clinical, and laboratory data on persons who do not enroll will be 
captured in an eCRF and entered into the ACTG database.  
 
6.2.2 Step 1 Entry Evaluations 
 
Step 1 entry evaluations must occur at least 24 hours after screening 
evaluations, unless otherwise specified.  
 
Participants are expected to begin treatment with SOF/VEL within 24 hours after 
registration and upon completion of entry evaluations. The first dose of SOF/VEL 
will be provided to the participant and observed by study staff.  
 
6.2.3 Step 2 Registration Evaluations 
 
Participants who meet criteria in section 4.3 will register to Step 2 on the same 
day of the last visit on Step 1 and be followed per the SOE.  
 
6.2.4 Post-Entry Evaluations 
 
Given the design of the MINMON strategy, there will be no on-treatment or EOT 
evaluations. See section 6.3.22 for post-entry site contact with participants via 
remote mechanism.  
 
Post-Treatment Evaluations  
Step 1: Following treatment completion at week 12, participants will undergo 
evaluations as outlined in the SOE 6.1-1. 
 
NOTE: If the participant comes in for the week 24 visit during the -14 days 
window (i.e., week 22), then the week 22 remote call is not needed.  
 
Week 24/SVR Evaluation Visit 
The week 24 visit (visit window: week 22-28) is ideally the visit where SVR 
should be assessed for all participants, and subsequently they will be registered 
to Step 2. However, if a participant misses the visit window (>week 28), the week 
24 visit will be considered a missed visit and he/she will need to be scheduled for 
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take place at any time point after week 28 and up to week 72 and is mandatory 
for the participant to be registered to Step 2.  
 
NOTE: Participants will be reminded of the week 24/SVR visit during the remote 
contact (at weeks 4 and 22), and participants only need to complete either the 
week 24 OR the SVR evaluation visit; they will not be required to complete both. 
If a participant completes week 24, his/her next visit will be at week 48 on Step 2. 
If a participant misses the week 24 visit and returns to the clinic for the SVR visit 
either at week 48 or 72, then only the SVR evaluations will be performed at that 
visit time point. Evaluations for weeks 48 or 72 will be performed at the next 
scheduled study visit. However, if a participant completes their SVR visit at week 
72, this visit will be the participants’ last study visit and they will not enter Step 2. 
 
Step 2 Registration  
Following completion of the SVR evaluation on Step 1 (Week 24 OR SVR visit), 
participants will be registered to Step 2 on that same day. Participants will 
undergo evaluations as outlined in the SOE 6.1-2, within the +28-days visit 
window, as appropriate for the visit.  
 
NOTE: Participants who register into Step 2 within the week 48 visit window will 
complete the week 48 and 72 visits. If a participant registers into Step 2 after the 
week 48 visit window, site staff should have the participant return to the clinic to 
complete week 72 (final study visit).  
 
6.2.5 Study Completion Evaluations 
 
For Step 2, week 72 ±28-days will be the final study visit for all participants, 
independent of the entry week for Step 2. 
 
For participants who do not enter Step 2, the final study visit will be the last visit 
they had on Step 1, regardless of when that occurred. 
 
6.2.6 Event-Driven Evaluations 
 
Step 1: Unplanned Study Visits 
Unplanned study visits should not occur after week 22 on Step 1. 
 
The purpose of unplanned visits, should they occur, is to address common 
toxicities. Participants will be provided with a telephone number that they can call 
if they are having any problems (e.g., headache, fever, nausea, etc.) during the 
study treatment period (day 0 through week 12). Participants will be connected to 
the study staff who will talk to them and try to resolve the issue over the phone, 
whenever possible. Only if the study staff feels further investigations are required 
to resolve the complaint, an unplanned study visit should be scheduled within 5 
days with the participant so that additional investigations, as deemed appropriate 
by the study staff, may be performed. It is possible no tests are ordered or tests 
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require any testing to be performed at these unplanned visits, if any laboratory 
test is ordered (e.g., safety labs), a plasma specimen should be stored. 
  
NOTE: If any laboratory, radiology, or other tests are ordered, they should be 
justified by medical need. Labs drawn for safety purposes are permitted. Any 
tests ordered are not meant to serve as an early indicator of a participant’s HCV 
treatment response. The performance of HCV RNA testing at unplanned study 
visits is strongly discouraged and should be discussed with the core team. The 
purpose of these unplanned visits, should they occur, is to deal with common 
toxicities.   
 
If a participant provides information about study treatment disposition, use (or 
change in use) of reportable concomitant medications, or gives information about 
reportable adverse events (e.g., AEs leading to change in study treatment 
regardless of severity grade) at this unplanned study visit, then this information 
should be captured on the appropriate eCRFs.   
 
Participants who become pregnant while on study medications or up to week 22 
should contact the site to schedule an unplanned study visit (see section 8.3 for 
details). 
 
6.2.7 Discontinuation  
 
Evaluations for Participants Who Do Not Start Study Treatment 
All eCRFs must be keyed for the period up to and including the entry visit. 
 
Premature Treatment Discontinuation  
Participants who plan or who have discontinued their study medication prior to 
completing the full 84-day course will have been instructed to contact the site to 
alert them of premature discontinuation. The site staff will not be aware of any 
treatment discontinuations unless the participants inform the site. These 
participants will be encouraged, like all other participants, to return for their SVR 
evaluation visit at week 24 and remain on the study through study completion. No 
adjustments to the timing of the SVR evaluation will be made for premature 
treatment discontinuation. Participants will be provided a number to call or send a 
text message informing the site of the stop date. 
 
6.3 
Instructions for Evaluations 
 
All clinical and laboratory information required by this protocol is to be present in the 
source documents. Sites must refer to the Source Document Guidelines on the DAIDS 
website for information about what must be included in the source document: 
https://www.niaid.nih.gov/sites/default/files/documents/sourcedocappndx.pdf. 
 
All stated evaluations are to be recorded on the eCRF unless otherwise specified. Refer 
to section 7.0 for information on the DAIDS AE Grading Table and AE reporting of AE 
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6.3.1 Documentation of Active HCV Infection 
 
Positive for HCV RNA >1000 IU/mL prior to study entry.  
Section 4.1.3 specifies assay requirements for HCV documentation. HCV 
documentation is not recorded on the eCRF. 
 
6.3.2 Documentation of HIV-1 Status 
 
Section 4.1.6 specifies assay requirements for HIV-1 documentation. HIV-1 
documentation is not recorded on the eCRF. 
 
6.3.3 Calculated FIBROSIS-4 (FIB-4) Score 
 
Calculated FIB-4 score is needed to determine cirrhosis status for all participants, 
as per the SOE, in order to evaluate other outcomes such as regression of liver 
disease.  
 
This calculation requires the following data: Participant age (years), serum 
alanine and aspartate aminotransferase level (U/L), and platelet count (109/L). 
 
Please refer to the A5360 PSWP for the website link to calculate the FIB-4 score. 
 
6.3.4 Model for End-Stage Liver Disease (MELD) Score 
 
The MELD score measures the mortality risk in participants with end-stage liver 
disease. It is used as a disease severity index to help prioritize allocation of 
organs for transplant. In order to calculate the MELD score, total bilirubin (mg/dl), 
sodium (mEg/L), INR, and serum creatinine (mg/dl) values are needed. 
 
Please refer to the A5360 PSWP for the website link to calculate the MELD 
score.  
 
6.3.5 Documentation of Cirrhosis Status  
 
Participants with calculated FIB-4 score of <3.25 are considered to be non-
cirrhotic. 
 
Participants with calculated FIB-4 score ≥3.25 are considered to have cirrhosis 
and must have a calculated CTP score of ≤6 (CTP A) to be considered a 
compensated cirrhotic. See section 6.3.6.   
 
6.3.6 Calculated Child-Turcotte-Pugh (CTP) Score 
 
Calculated CTP score is needed only for participants who are considered 
cirrhotics as determined by the FIB-4 score (≥3.25) as per the SOE. CTP score 
must be ≤6 corresponding to Class A to be included in the study.  


 
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This calculation requires the following data: total bilirubin (mg/dl), albumin (g/dl), 
INR, evaluation for ascites (absent, slight, or moderate), evaluation for hepatic 
encephalopathy as per West Haven criteria (none, mild to moderate [Grade1-2], 
severe [Grade 3-4]). 
 
Please refer to the A5360 PSWP for the website link to calculate the CTP score. 
 
6.3.7 Liver Elastography 
 
If available, liver elastography measurement will be captured at entry visit. Liver 
elastography data/values from the previous 3 years will be accepted. This will not 
be required for study entry. Where available, liver elastography will be repeated 
per the SOE. See A5360 MOPS for a list of liver elastography methods.  
 
6.3.8 Medical History 
 
The medical history must include all signs and symptoms regardless of grade 
and all diagnoses identified by the ACTG criteria for clinical events and other 
diagnoses regardless of grade within 30 days prior to entry. In addition, the 
following diagnoses should be reported regardless of when the diagnosis was 
made: 
• 
AIDS-defining conditions (only for HIV-1 co-infected participants) 
• 
Bone fractures (verbal history accepted) 
• 
Coronary heart disease 
• 
Cancer (exclusive of basal/squamous cell skin cancer) 
• 
Diabetes 
• 
Tuberculosis 
• 
Chronic HCV (If available, appropriate documentation from medical records 
of chronic HCV-infection, defined as having a documented HCV-positive 
antibody serology for greater than 6 months.) 
• 
Chronic HBV 
• 
Substance use (injection, non-injection drugs, and alcohol) captured via the 
WHO ASSIST instrument 
 
Any allergies to any medications and their formulations must also be 
documented.  
 
6.3.9 Medication History 
 
A medication history must be present, including start and stop dates.  
 
Table 6.3.9-1 Required Medication History  
 


 
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Medication Category 
Complete History or 
Timeframe 
Antiretroviral therapy 
Within 90 days before 
study entry 
Prescription drugs for treatment 
of opportunistic infections 
Within 35 days before 
study entry 
Prescription drugs for 
prophylaxis of opportunistic 
infections 
Within 35 days before 
study entry 
Prescription drugs (other) 
Within 35 days before 
study entry 
Non-prescription drugs 
Within 35 days before 
study entry 
Acid suppressing medications 
such as proton pump inhibitors 
(PPIs) and/or H2 inhibitors 
Within 35 days before 
study entry 
Vaccinations 
Within 35 days before 
study entry 
Sex-hormone medications or 
sex-hormone analogues or 
antagonists* 
Last 12 months except as 
noted below 
*Includes: hormone-releasing IUDs (e.g., Mirena inserted in the last 5 years); 
oral, injectable, implanted, or patch contraceptives; vaginal ring, creams, or 
inserts; estrogen, progesterone, or testosterone therapy; leuprolide or other 
synthetic gonadotropin-releasing hormone; tamoxifen, raloxifene, aromatase 
inhibitors or any other androgen, estrogen, or progesterone analogue or 
antagonist therapy.  
 
6.3.10 Clinical Assessments 
 
Complete Physical Exam 
A complete physical examination must be performed at screening and is to 
include at a minimum an examination of the skin, head, mouth, and neck; 
auscultation of the chest; cardiac exam; abdominal exam; and examination of the 
lower extremities for edema. The complete physical exam will also include signs 
and symptoms, diagnoses, and vital signs (height, weight, temperature, pulse, 
respiration rate, and blood pressure). 
 
Targeted Physical Exam 
A targeted physical examination should be performed at entry, week 24/SVR 
evaluation visit and weeks 48 and 72, and should include vital signs (weight, 
temperature, pulse, respiration rate, and blood pressure), and is to be driven by 
any previously identified or new AE/targeted condition (as described in below 
bullets), that the participant has experienced within 14 days prior to study 
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Post entry, record the following targeted events regardless of grade: 
• 
Uterine pregnancy 
• 
AIDS-defining conditions (refer to the CDC HIV Classification and the WHO 
Staging System for HIV Infection and Disease) 
• 
Tuberculosis 
• 
Chronic HBV 
• 
Ascites 
• 
Hepatic Encephalopathy 
  
Refer to section 7.2 for AE collection requirements.   
 
Height  
Height (in cm) will be collected once at study screening. 
 
Weight 
Weight (in kg) will be collected at study screening, entry, week 24/SVR 
evaluation visit, and weeks 48 and 72. 
 
Concomitant Medications 
At entry and at the week 24/SVR evaluation visit, new and discontinued 
concomitant medications should be recorded on the eCRFs. See section 5.4 for 
concomitant medications. 
 
Study Treatment (Intervention) Modifications 
When the participant takes the last tablet of each bottle of SOF/VEL, they will be 
instructed to contact the site to report the treatment stop date. This information 
self-reported by the participant should be captured on the eCRF when reported 
outside of and during the week 24/SVR evaluation visit. See A5360 MOPS for 
additional details.  
 
At the week 24/SVR evaluation visit, record all study drug modifications, 
including participant-initiated modifications, inadvertent and deliberate 
interruptions of more than 7 days. Record permanent discontinuation of study 
treatment (see section 6.2.7). 
 
6.3.11 Laboratory Evaluations 
 
At screening and entry, all laboratory values must be recorded on the eCRF. For 
post-entry assessments, all laboratory values for hemoglobin, AST, ALT, blood 
urea nitrogen (BUN), serum creatinine, total bilirubin, sodium, INR, albumin, and 
platelets regardless of grade must be recorded on an eCRF. Additional reporting 
of abnormal laboratory findings should be performed as per requirements in 
section 7.2. 
Hematology 
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platelets. 
 
Liver Function Tests 
AST (SGOT), ALT (SGPT), total bilirubin and albumin. 
 
Blood Chemistries 
Serum creatinine, sodium, BUN 
 
Creatinine Clearance (CrCl) 
CrCl will be calculated throughout the study using Cockcroft-Gault method. Refer 
to the Cockcroft-Gault calculator located on the FSTRF web site. (Please refer to 
the A5360 PSWP for the website link to calculate CrCl using the Cockcroft-Gault 
calculator.) 
 
International Normalized Ratio (INR) 
This will be performed at a local laboratory. 
 
Pregnancy Test 
For women with reproductive potential: Serum or urine β-HCG. (Urine test must 
have a sensitivity of <25 mIU/mL.) Record pregnancy and pregnancy outcome 
per section 8.0.   
 
HBV Panel 
A HBV panel that includes hepatitis B surface antibody (HBsAb), hepatitis B core 
antibody total or IgG (HBcAb), and HBsAg will be performed during screening. 
HBV infection status must be confirmed prior to study entry. The panel must be 
performed at a laboratory that possesses Clinical Laboratory Improvement 
Amendments (CLIA) certification or its equivalent or at a DAIDS approved 
laboratory.   
 
Results must be recorded on an eCRF.  
 
NOTE: Active HBV infection is defined by the presence of hepatitis B surface 
antigen in serum (HBsAg+) at screening.  
 
Table 6.3.11-1 Enrollment Eligibility Based on HBV Panel Results  
HBsAg 
HBsAb 
HBcAb total or IgG 
Status 
Positive 
Negative 
Positive 
Active HBV infection; NOT 
ELIGIBLE  
Negative 
Positive 
Positive 
Prior HBV infection with 
immunity;  ELIGIBLE 
Negative 
Positive 
Negative 
Prior vaccination with immunity;  
ELIGIBLE 
Negative 
Negative 
Positive 
Isolated Hepatitis B core 
antibody.  Prior HBV infection 
without immunity;  ELIGIBLE 


 
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6.3.12 Immunologic Studies (For HIV co-infected participants) 
 
CD4+ 
Obtain absolute CD4+ count within 90 days prior to entry from a laboratory that 
possesses a CLIA certification or equivalent.  
 
6.3.13 Virologic Studies 
 
Plasma HIV-1 RNA (For HIV Co-infected Participants) 
Screening HIV-1 RNA must be performed within 90 days prior to study entry by a 
laboratory that possesses a CLIA certification or equivalent.  
 
HCV RNA 
Screening HCV RNA by PCR must be obtained by any FDA-approved test for 
quantifying HCV RNA at any local laboratory that has a CLIA certification or its 
equivalent. If no historical documentation is available, the screening HCV RNA 
must be obtained within 35 days prior to study entry. 
 
All other samples will be collected per SOE. Only samples from participants who 
have achieved SVR will be collected at weeks 48 and 72 and tested for the 
presence of HCV RNA.  
 
HCV RNA samples on study will be processed and shipped to the designated 
A5360 VSL for real-time quantitative HCV RNA analysis. 
 
6.3.14 Stored Plasma/PBMCs/Serum 
 
Stored plasma, PBMCs, and serum will be collected at the indicated visits for 
future HCV/HIV studies and shipped according to the A5360 Laboratory  
Processing Chart (LPC). Stored specimens will be used after study completion 
for HCV genotyping/sequencing to assess re-infection versus relapse and 
estimate SVR by genotype. 
 
Further, the NS5A and NS5B regions of HCV will be sequenced for the earliest 
sample where HCV RNA is detected post-SVR and the corresponding entry 
sample will also be sequenced. Sequence data will assist in discriminating 
between reinfection (entry and post-SVR sequences are not related) versus 
relapse (entry and post-SVR sequences are identical). Incidence of reinfection 
will be calculated following the completion of sequencing.   
 
Those who do not achieve SVR (SVR non-responders) will have both baseline 
and SVR specimens tested for HCV RASs by sequencing the NS5A and NS5B 
regions.  
 
Any specimens collected during unplanned visits will be stored. See section 
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6.3.15 Questionnaires 
 
Adherence Assessment 
Adherence will be captured at the week 4 remote contact (see section 6.3.22) 
and week 24/SVR evaluation visit (i.e., week 22 or beyond). At both 
assessments, participants will be asked to estimate their adherence using Likert-
type questions (all, most, half, some, or none). At the SVR visit, participants will 
also be asked to indicate the percentage of study medication that they actually 
took on a visual analog scale. At the week 4 remote contact assessment and 
week 24/SVR evaluation visit, participants who report less than perfect 
adherence will be asked about barriers to adherence. 
 
Health Outcomes Questionnaire (EQ-5D) 
The EQ-5D is a validated instrument used to collect data about quality of life 
(http://www.euroqol.org). The instrument asks questions and each has three 
possible responses (EQ5D-3L version). The instrument asks respondents to 
comment on their degree of mobility, self-care, usual activities, pain/discomfort, 
and anxiety/depression, and then ask participants to record their current health-
related quality of life state using a vertical visual analogue scale (0-100 range). 
The instrument has been translated into a variety of languages and is available 
as a paper form, a computer-based form, a tablet/cell phone form, or as an 
interview.  
 
Responses must be recorded on an eCRF from the entry visit and week 24/SVR 
evaluation, and weeks 48 and 72 visits. In addition, responses must be recorded 
in the event of an unplanned study visit. 
 
Health Care Utilization Questionnaire 
The health care utilization questionnaire solicits participant-reported health care 
utilization in the past 4 weeks including: 1) nights spent in a hospital bed, 2) visits 
to an emergency department, and 3) visits to a doctor’s office. This questionnaire 
will be administered during visits at entry, week 24/SVR evaluation, and weeks 
48, 72, and any unplanned visits. Responses must be recorded on an eCRF. 
 
Substance Use Questionnaire 
The substance use questionnaire will be administered at entry, week 24/SVR 
evaluation and weeks 48 and 72 visits. The Alcohol, Smoking and Substance 
Involvement Screening Test (ASSIST) survey that was developed for the WHO 
by an international group of researchers and clinicians as a technical tool to 
assist with early identification of substance use-related health risks and 
substance use disorders will be used. This tool has been validated globally and 
captures information on alcohol, smoking, and injection and non-injection drug 
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6.3.16 HCV Therapy Dispensed/First Dose Observed 
 
The entire quantity of study-provided drug (84 tablets) will be dispensed at the 
entry visit (week 0). Study staff will observe the first dose taken by the participant 
before he/she leaves the site and record this observation on an eCRF. Refer to 
section 5.0 for details on study product dispensation.  
 
6.3.17 Adherence Education and Counseling 
 
Adherence education and counseling will be conducted for all participants prior to 
entry. Adherence education and counseling is not recorded on the eCRF.   
 
See the A5360 MOPS for further details. 
 
6.3.18 Pregnancy Prevention Counseling 
 
Pregnancy prevention counseling will be conducted for all participants at 
screening and entry. Pregnancy prevention counseling is not recorded on the 
eCRF.  
 
6.3.19 Cirrhosis Counseling 
 
All compensated cirrhotics will be counseled on secondary prevention and long-
term surveillance of liver disease according to the SOE. Cirrhosis counseling is 
not recorded on the eCRF.  
 
See the A5360 MOPS for further details.    
 
6.3.20 HCV Risk-reduction Counseling  
 
HCV risk-reduction counseling will be administered to all participants, per the 
SOE. See the A5360 MOPS for further details.    
 
6.3.21 Locator Information 
 
At study entry, all participants will be asked to list their primary mode of contact 
(e.g., telephone, email, text, or social media) and their secondary mode of 
contact. The site will capture these options for mode of contact (but will not 
record any participant locator this information on any eCRF), and use them to 
contact study participants without requiring them to come in to the clinic. Sites 
will also capture information on another person that the site can contact if the 
participant cannot be reached (e.g., spouse, friend, neighbor, etc.); information 
on the secondary contact will not be recorded on any eCRF. 
 


 
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6.3.22 Remote Contact with Participants Outside of Planned Clinic Visits 
 
When contacting participants remotely, sites will have the flexibility to make 
adjustments to the mode of contact utilized at their discretion and at the 
participant’s convenience – the only mode that will not be allowed is to schedule 
clinic visits in place of the remote contact. Sites will also be able to use different 
modes to contact different participants. Additionally, how the participant was 
contacted (i.e., mode of contact) will be collected on the eCRF.  
 
Data that will be captured from the participant during the week 4 remote contact 
is whether the participant is taking study medication (i.e., adherence), in the prior 
4 weeks. All participants will receive an individually tailored message, based on 
their adherence, which will be read or written to them in order to promote and/or 
encourage adherence through the end of treatment. The message will highlight 
the benefit of treatment for HCV and the importance of adherence and will be 
tailored to each participant’s response as to how well he/she is adhering to the 
HCV treatment regimen. Additionally, at both weeks 4 and 22, locator information 
will be updated (if anything has changed) and participants will be reminded to 
return for their SVR evaluation visit. Sites will be allowed to contact and collect 
participant’s responses on adherence and to update his/her locator information 
using any of the options listed above, namely phone call, text message, email, or 
social media (e.g., WhatsApp, Facebook Messenger, Twitter, etc.; for a complete 
list, please refer to the MOPS). If the participant comes in for the week 24 visit 
prior to the completion of the week 22 remote call, or if the participant has 
completed the discontinuation visit, then the week 22 remote call is not needed.  
 
The remote contact is not designed to assess concomitant medications or AEs. 
At the end of each remote contact, participants will be reminded that the 
information that they shared will not be communicated to the study team and that 
if they have concerns about symptoms or study questions they should contact 
the site via the telephone number provided by the site. This information should 
be reported in a medical record then reviewed and entered into an eCRF at the 
week 24/SVR evaluation visit. 
 
Since it is common for participants to lose mobile phones or change service 
providers in a 6-month period, it is critical to ensure that locator information is 
kept up-to-date to ascertain SVR status. Locator information will be maintained 
securely by sites and specific locator information will not be recorded onto an 
eCRF. However, the parts of the locator information that were updated and the 
mode of contact used to update this information will be recorded on an eCRF. 
 
Participants will be provided with a telephone number to contact the study staff if 
they are experiencing any side effects or have any safety concerns. If the study 
staff contacted determines that the issue cannot be resolved over the phone, an 
unplanned study visit will be scheduled, as described in section 6.2.6. If 
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to the call should be reported in the participant medical record and reviewed at 
week 24/SVR evaluation visit and entered into the eCRF.  
 
See the A5360 MOPS for further details, including a script to be used by site staff 
when contacting participants. 
 
7.0 
ADVERSE EVENTS AND STUDY MONITORING 
 
7.1 
Definition of Adverse Events 
 
An AE is any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or diagnosis that occurs in a study participant during the conduct of 
the study REGARDLESS of the attribution (i.e., relationship of event to medical 
treatment/study product/device or procedure/intervention). This includes any occurrence 
that is new in onset or aggravated in severity or frequency from the baseline condition.  
 
7.2 
Adverse Event Collection Requirements for This Protocol 
 
Post-entry, all AEs must be recorded on the eCRFs if any of the following criteria have 
been met. 
• 
All grade ≥ 3 AEs 
• 
All AEs that led to a change in study treatment/intervention regardless of grade 
• 
All AEs meeting SAE definition or EAE reporting requirement 
 
NOTE: SAEs or events meeting EAE reporting requirements should also be entered into 
the DAIDS Adverse Experience Reporting System (DAERS), an internet-based reporting 
system. 
 
NOTE: At week 24/SVR evaluation visit, information on any AEs participants may have 
experienced during the prior 24 weeks (particularly while on study medication) will be 
collected unless this information was already obtained during an unplanned study visit. 
 
All AEs that are reported must have their severity graded. To grade AEs, sites must refer 
to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017, which can be 
found on the DAIDS RSC website at http://rsc.tech-res.com/clinical-research-
sites/safety-reporting/daids-grading-tables. 
 
Serious Adverse Events (SAEs) 
A SAE is defined as any untoward medical occurrence 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 
• 
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result in death or hospitalization but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above). 
 
7.3 
Expedited Adverse Event (EAE) Reporting to DAIDS 
 
7.3.1 Expedited Reporting of Adverse Events to DAIDS 
 
Requirements, definitions and methods for expedited reporting of Adverse 
Events (AEs) are outlined in Version 2.0 of the DAIDS EAE Manual, which is 
available on the RSC website at http://rsc.tech-res.com/clinical-research-
sites/safety-reporting/manual. 
 
DAERS must be used for EAE reporting to DAIDS. In the event of system 
outages or technical difficulties, EAEs may be submitted using the DAIDS EAE 
Form. This form is available on the DAIDS RSC website at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting/daids/paper-eae-reporting. 
 
For questions about DAERS, please contact NIAID CRMS Support at 
CRMSSupport@niaid.nih.gov. Please note that site queries may also be sent 
from within the DAERS application itself. 
 
For questions about expedited reporting, please contact the DAIDS RSC Safety 
Office at (DAIDSRSCSafetyOffice@tech-res.com). 
 
7.3.2 Reporting Requirements for this Study 
 
• 
The SAE Reporting Category, as defined in Version 2.0 of the DAIDS EAE 
Manual, will be used for this study.  
• 
The study agents for which expedited reporting are required are: 
Sofosbuvir/Velpatasvir (SOF/VEL) FDC 
• 
In addition to the EAE Reporting Category identified above, other AEs that 
must be reported in an expedited manner are: all cancers, myopericarditis 
events, hepatic failures, and autoimmune diseases. 
  
7.3.3 Grading Severity of Events 
 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017, 
must be used and is available on the DAIDS RSC Web site at http://rsc.tech-
res.com/clinical-research-sites/safety-reporting/daids-grading-tables. 
 
7.3.4 Expedited AE Reporting Period 
 
• 
The expedited AE reporting period for this study is week 0 to week 24/SVR 
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• 
After the protocol-defined AE reporting period, unless otherwise noted, only 
suspected, unexpected serious adverse reactions (SUSARs), as defined in 
Version 2.0 of the EAE Manual, will be reported to DAIDS if the study staff 
become aware of the events on a passive basis (from publicly available 
information). 
 
7.4 
Study Monitoring 
 
The Protocol Core Team will monitor the conduct and safety of the study via regular 
summaries of screening, accrual, data delinquency, study and study treatment 
discontinuation, data and sample completeness with attention to evaluation and time of 
SVR evaluation, and SAEs.  
 
The DAIDS clinical representative will review and assess EAE reports for potential 
impact on the study participant safety and protocol conduct as per DAIDS policies, 
guidance documents, and SOPs as applicable. Additionally, the DAIDS clinical 
representative will receive aggregated SAE summaries prepared quarterly by the SDAC, 
as part of the core team monitoring referenced above. 
 
The study will undergo interim review at least annually by an ACTG-appointed Study 
Monitoring Committee (SMC). The first interim review will occur no more than one year 
after the enrollment of the first study participant or 6 months after 25% of the study 
sample (100 participants) have completed 12 weeks on study, whichever occurs earlier. 
An interim review may also be convened if a concern is identified by the DAIDS clinical 
representative, the study chairs, or study statistician in consultation with the team. See 
Section 10 for statistical and other considerations related to interim monitoring. 
Detailed plans for study monitoring will be outlined in a Study Monitoring Plan developed 
by the Statistical and Data Management Center (SDMC) prior to enrollment of the first 
participant. 
 
Items for SMC interim review include the following: screening and accrual, baseline 
characteristics of study sample, data (and specimen) completeness, premature study 
treatment and study discontinuation, unplanned study visits, safety (serious and other 
adverse events), evaluability for primary efficacy outcome, and for interim reviews 
including efficacy outcome: SVR outcome estimation. 
 
8.0 
CLINICAL MANAGEMENT ISSUES 
 
8.1 
Toxicity  
 
Criteria for participant management, dose interruptions, dose adjustments and 
discontinuation, or changes in treatment will be described only for toxicities attributable 
to study drugs (SOF/VEL). The grading system for drug toxicities is located in the DAIDS 
AE Grading Table (see section 7.2).   
 
NOTE: The team must be notified via e-mail within 72 hours regarding toxicities that 
result in a change in study regimen (actg.corea5360@fstrf.org). 


 
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It is possible that some participants will experience transient or prolonged AEs during the 
study. However, it is important to note that, in this trial, there are no scheduled on-
treatment visits and hence, participants must call the site and schedule unplanned study 
visits in order for AEs to be identified. AE-related unplanned study visits will be handled 
as listed below. However, at week 24, information on any AEs participants may have 
experienced during the prior 24 weeks, particularly while on study medication, will be 
collected. 
 
8.2 
Management of Side Effects of SOF/VEL  
 
There are no signature abnormalities associated with SOF/VEL. If an SAE occurs, the 
site investigator has the option to discontinue study treatment. However, prior to the 
discontinuation of study drugs, the study core team should be contacted by email 
(actg.corea5360@fstrf.org).  
 
Participants who meet any of the following laboratory criteria should stop treatment with 
SOF/VEL: 
• 
Confirmed elevation of ALT and/or AST >5 x entry values measured while on study 
treatment measured at unplanned study visits. 
• 
Confirmed direct bilirubin 3 x ULN and >2.0 mg/dL 
• 
Any Grade 3 or greater rash associated with constitutional symptoms assessed as 
related to treatment with SOF/VEL. 
• 
Any Grade 4 event assessed as related to treatment with SOF/VEL 
 
Dose modification of SOF/VEL will not be allowed in the study. If SOF/VEL is 
discontinued for toxicity reasons, it should not be restarted.  
 
NOTE: Grades 1 and 2 AEs associated with SOF/VEL require no change in study 
treatment. 
 
8.3 
Pregnancy  
 
Pregnancy will result in immediate discontinuation of the study medication and initiation 
of counseling regarding the lack of information on safety of SOF/VEL in pregnancy. 
Participants who become pregnant while on study should contact the site to schedule an 
unplanned study visit (only up to week 22) and will be followed on study/off-treatment 
until study completion. A visit following the end of pregnancy will be conducted for 
evidence of AEs in the participant, and an outcome eCRF will be completed. Male 
participants whose partners become pregnant will continue treatment as outlined in the 
SOE. 
 
If a female participant has completed the study or chooses to discontinue from the study 
before the end of the pregnancy, site staff should request permission to contact her 
regarding pregnancy outcomes at the end of pregnancy. If the information is obtained, 
pregnancy outcomes will be submitted on an eCRF at the end of the pregnancy. 
 


 
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Pregnancy and pregnancy outcome will be recorded on the eCRFs Pregnancies that 
occur on study should be reported prospectively to The Antiretroviral Pregnancy 
Registry. More information is available at www.apregistry.com. Phone: 800-258-4263; 
Fax: 800-800-1052. (For studies conducted at sites outside the United States: Report to 
The Antiretroviral Pregnancy Registry - Telephone: 910-679-1598; Fax: 44-1628-789-
666 or 910-256-0637.) 
 
9.0 
CRITERIA FOR DISCONTINUATION 
 
9.1 
Permanent and Premature Treatment Discontinuation 
 
• 
Drug-related toxicity (see section 8.1 Toxicity). 
• 
Requirement for prohibited concomitant medications (see section 5.4). 
• 
Pregnancy in a female participant. 
• 
Breastfeeding. 
• 
Completion of treatment as defined in the protocol. 
• 
Participant request to discontinue for any reason. 
 
NOTE: It is important to determine whether the treatment discontinuation is 
primarily due to an AE, lack of efficacy, or other reason. 
• 
Clinical reasons believed life threatening by the physician, even if not addressed in 
the toxicity section of the protocol. 
 
9.2 
Premature Study Discontinuation 
 
• 
Request by the participant to withdraw. 
• 
Request of the primary care provider if s/he thinks the study is no longer in the best 
interest of the participant. 
• 
Participant judged by the investigator to be at significant risk of failing to comply with 
the provisions of the protocol so as to cause harm to self or seriously interfere with 
the validity of the study results. 
• 
At the discretion of the IRB/Ethics Committee, Food and Drug Administration (FDA), 
NIAID, Office for Human Research Protections (OHRP), other government agencies 
as part of their duties, investigator, or industry supporter.  
 
10.0 
STATISTICAL CONSIDERATIONS  
 
10.1 
General Design Issues 
 
This is a single-arm study of 400 participants, to evaluate the feasibility, safety, and 
efficacy of a MINMON strategy of delivering interferon and RBV-free, pan-genotypic 
DAA therapy to qualifying persons with active HCV. The outcomes of this study may be 
used to inform the feasibility and utility of a future randomized controlled trial including a 
study arm with the MINMON strategy. Because this study includes only one arm, there is 
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The primary completion date (PCD) for each participant will be timed to be the date 
when the SVR evaluation takes place. As defined below, SVR evaluation will take place 
at least 22 weeks following study entry, but may take place any time up to 76 weeks 
following study entry (i.e., the final study visit evaluation). 
Following SVR evaluation, participants will enter Step 2 for post-SVR evaluation follow-
up for secondary and exploratory objectives.  
 
10.2 
Outcome Measures  
 
10.2.1 Primary Outcome Measures 
 
10.2.1.1 Efficacy: Sustained virologic response defined as <LLOQ of HCV RNA 
in plasma from the earliest sample drawn at least 22 weeks following 
study entry. Missing results will be treated as SVR non-responders. 
 
10.2.1.2 Safety: SAEs as defined by International Council for Harmonization 
(ICH) guidelines occurring from study entry until 24 weeks following 
study entry. 
 
10.2.2 Secondary Outcome Measures  
 
10.2.2.1 Participant with at least one unplanned clinic visit prior to SVR 
evaluation 
 
10.2.2.2  Reportable AEs (as per section 7.2 of the protocol) not qualifying as 
SAEs (see primary safety outcome above), occurring from study entry 
until 24 weeks following study entry. 
 
10.2.2.3  Premature discontinuation of study treatment, as defined by self-report 
by study participants 
 
10.2.3 Other Outcome Measures 
 
10.2.3.1  HCV reinfection defined as detectable HCV RNA and HCV sequence 
from subsequent to evaluation of SVR response, distinct from the 
baseline sequence and defined only among SVR responders 
 
10.2.3.2  Change in FIB-4 between study entry and final study evaluation, 
defined only among SVR responders 
 
10.2.3.3 Treatment emergent RASs among SVR non-responders 
 
10.2.3.4 Quality of life (health related utility) before and after HCV cure 
 
10.2.3.5 Cost per SVR attained- both globally and stratified by country - 
calculated using country-specific costs and expressed in US$ 2017. 
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10.2.3.7 Number and timing of unplanned visits, number of types of evaluations 
at unplanned visits  
 
10.2.3.8 Adherence to study treatment as self-reported by participants 
 
10.3 
Registration and Stratification 
 
There is no randomization to this single-arm study. Eligible participants will enroll to Step 
1 and then have the following required evaluations as described in section 6. The study 
will use stratification factors to limit enrollment to Step 1 by certain subgroups. These 
stratification factors include geographic location (limited to no more than 132 participants 
being enrolled from US-based clinic sites), HIV-1 infection (limited to no more than 200 
participants being HIV-1 positive within the overall study sample) and cirrhosis status 
(limited to no more than 80 participants within the overall study sample having 
compensated cirrhosis). There are no additional restrictions regarding participants who 
are both HIV-co infected and have compensated cirrhosis and/or geographic distribution 
of those participants. Step 2 enrollment occurs following SVR evaluation and is for post 
SVR evaluation follow-up for selected secondary and exploratory objectives. 
 
10.4 
Sample Size and Accrual  
 
The sample size for this single-arm study is 400 participants.  
 
This sample size was chosen for benchmark properties listed below regarding the use of 
efficacy data from this study to informing the utility and feasibility of future studies of the 
MINMON approach, and the precision (based on CI width) about SVR efficacy outcome 
estimates. 
 
Table 10.4-1 below describes SVR benchmarks and their properties. 
 
The high benchmark is defined as when the lower confidence limit of the 2-sided 95% CI 
about the SVR estimate is strictly greater than 96%. Observing 392 or more SVR 
responders out of 400 participants (i.e., ≥98% SVR responders) would meet this 
benchmark. Under a true SVR rate of 97%, there is only a small probability (0.15) of 
observing this benchmark with the study sample size of 400. However, as the true SVR 
rate becomes higher, the probability of observing this benchmark also increases (while 
holding the sample size at 400 participants). For instance, if the true SVR rate were 
98.5%, then there is 0.85 probability of observing this high benchmark in the proposed 
study sample size of 400.  If a high benchmark were observed, then a future RCT may 
not be needed, as the high benchmark implies that the SVR for the MINMON strategy 
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The low benchmark is defined as when the upper confidence limit of the 2-sided 95% CI 
about the SVR estimate is strictly less than 95%. Observing 371 or fewer SVR 
responders out of 400 participants (i.e., ≤92.8% SVR responders) would meet this 
benchmark. Properties of possible scenarios are given in Table 10.4-1. 
 
If neither the high nor low benchmark is met, a future RCT of the MINMON approach 
versus SOC may be desired, and efficacy estimates from this study could be used to 
inform the design and sample size of that study. 
The low and high SVR benchmarks described above and in Table 10.4-1 below were 
chosen to represent what is currently thought to be reasonable SVR rates based on 
studies presented and published, including clinical trials, as well as studies reporting use 
of this DAA regimen outside the context of a clinical trial. 
 
Properties of this study’s sample size regarding probability of not observing either 
benchmark 
Table 10.4-2 below summarizes the various probabilities that neither of the benchmarks 
(HIGH or LOW, as described above), are observed under a range of various true rates of 
SVR. 
 
Table 10.4-1. SVR benchmarks and their properties 
Benchmark 
Benchmark 
Definition 
(note: CI = 
confidence 
interval) 
Observed 
conditions for 
meeting 
benchmarks 
given proposed 
sample size of 
400 participants 
Hypothesiz
ed true 
SVR rates  
Probability of 
observing 
benchmark 
given 
hypothesize
d true SVR 
rate and 
proposed 
sample size 
How observing 
different 
benchmarks 
could inform 
design of a 
future study 
HIGH 
Lower 
confidence limit 
of 2-sided 95% 
CI about SVR 
estimate is 
strictly greater 
than 96% 
Number of 
participants with 
SVR >392 out of 
400 
(or conversely, 8 
or fewer SVR 
non-responders) 
96.5% 
.06 
A future RCT 
may not be 
needed as this 
benchmark 
implies  
MINMON SVR 
to be greater 
than 96% 
97% 
.15 
98% 
.59 
98.5% 
.85 
LOW 
Upper 
confidence limit 
of 2-sided 95% 
CI about the 
SVR estimate is 
strictly lower 
than 95% 
Observed 
number of 
participants with 
SVR <371 out of 
400 (or 
conversely, 29 
or more SVR 
non-responders) 
94% 
.17 
A future RCT 
may not be 
desired as this 
benchmark 
implies 
MINMON SVR 
to be lower than 
95%. 
93% 
.45 
92% 
.74 
 


 
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Table 10.4-2. Probabilities of not observing either HIGH or LOW benchmark under sample size 
of 400 and various true SVR rates 
Hypothesized True 
SVR rates  
Probability of not observing either benchmark 
as defined above (i.e., observed number of 
SVR responders is between 372 – 391, 
inclusive, out of 400 participants) 
90% 
.023 
91% 
.092 
92% 
.264 
93% 
.550 
94% 
.829 
95% 
.968 
96% 
.978 
97% 
.849 
98% 
.407 
99% 
.021 
 
Table 10.4-3 below summarizes the precision about the primary efficacy outcome of 
SVR (as measured by the width of the 95% CI about the SVR estimate), and location of 
95% CI limits, based on various observed SVR rates and 400 individuals. The 95% 
confidence intervals were calculated with the binomial distribution according to the 
method of Wilson (Score based intervals). 
 
Table 10.4-3. Summary of a range of observed SVR rates and their impact on the precision of 
the 95% CI about the observed/estimated SVR rate 
Observed SVR rate 
among n=400 
SVR 95% CI lower 
confidence limit 
SVR 95% CI upper 
confidence limit 
Precision of SVR 
estimate (95% CI 
width in percentages 
points) 
90% 
86.7% 
92.6% 
5.9 
91% 
87.8% 
93.4% 
5.6 
92% 
88.9% 
94.3% 
5.4 
93% 
90.1% 
95.1% 
5.0 
94% 
91.2% 
95.9% 
4.7 
95% 
92.4% 
96.7% 
4.3 
96% 
93.6% 
97.5% 
3.9 
97% 
94.8% 
98.3% 
3.4 
98% 
96.1% 
99.0% 
2.9 
99% 
97.5% 
99.6% 
2.2 
 
The sample size calculation has not been adjusted for losses to study follow-up as the 
definition of the primary efficacy outcome includes imputing missing evaluations as SVR 
non-responders. The impact of missingness contributing to the (lowering of the) SVR 
response rate will be addressed by both enumerating what led to non-SVR responder 
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RNA values observed >the assay LLOQ, early stopping of study treatment (e.g., for 
intolerability, etc.). 
 
Assuming uniform accrual of 25 participants per month, total accrual to the study would 
be completed in 16 months. If initial accrual is assumed to be slower, at rates of 10 
participants per month for the first 6 months, 15 participants per month for the next 6 
months, and 20 participants per month for the remaining time, the total accrual time 
would be about 24 months. 
 
10.5 
Data and Safety Monitoring 
 
10.5.1 Interim Monitoring Guidelines 
 
This study will be formally monitored at least annually by an ACTG-appointed 
SMC (via the standing committee for the Hepatitis TSG). The first interim review 
will occur no more than one year after the enrollment of the first study participant 
or 6 months after 25% of the study sample (100 participants) have completed 12 
weeks on study, whichever occurs earlier. 
 
A planned interim review for efficacy will be performed when SVR outcomes are 
available for approximately 100 participants, but could occur earlier (under case 
of a faster than anticipated accrual rate). The team wishes that an interim look at 
efficacy occur while the study is still accruing, so that if SVR rate is unacceptably 
low (i.e., futility), that there is still an opportunity to intervene before accrual to the 
study is completed.   
 
For instance, assuming uniform accrual of 25 participants per month and SVR 
evaluation happening 24 weeks following study entry, the planned interim review 
for efficacy would occur around month 12 since study accrual commenced, with 
approximately 300 participants accrued, 100 participants with SVR outcome 
available, and 100 participants remaining to be accrued. Assuming the slower but 
increasing accrual rate over time and same timing of SVR evaluation, the 
planned interim review for efficacy would occur approximately 17 months 
following study opening, with approximately 265 participants accrued, 105 
participants with SVR outcome, and 135 participants remaining to be accrued. 
 
Consideration would be given to closer monitoring or stopping the study if there 
is early and strong evidence to exclude the SVR rate from being 95% or higher 
(i.e., upper confidence bound on a 1-sided 99.9% CI is lower than 95%). With 
100 participants, this boundary would be met if the observed SVR rate were 86% 
or lower (which corresponds to 14 or more SVR non-responders out of 100). For 
additional information, SVR estimates will be provided separately for subgroups 
defined by geographical location stratification factor (ie, US versus non-US). 
 
However, if the SMC sees early benefit of the MINMON intervention, the team 
intends the study to proceed with full accrual and follow-up in order to confirm 
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outcomes. At interim reviews, SVR will be calculated only among those with 
potential to contribute to SVR (by having at least 22 weeks elapsed since study 
entry). Imputation of missing SVR evaluation as non-SVR response will only 
occur for participants for whom more than 76 weeks since study enrollment has 
elapsed. In other words, early study discontinuations prior to week 22 will not be 
counted in SVR estimation at interim review, as these could bias the estimation 
of SVR towards futility. Instead, these early study discontinuations prior to week 
22 (before available for SVR evaluation), and others missing SVR evaluation, will 
contribute to the interim monitoring trigger below. 
 
If the analysis sample for the initial planned review for efficacy as outlined above 
includes fewer than 40% participants from non-US clinical research sites, then a 
second planned review of efficacy will be triggered when SVR outcomes are 
available on approximately 230 participants (with the upper limit of US 
participants of 132, this estimates at least 40% non-US representation in the 
second efficacy look interim analysis sample). The same analysis plan and 
monitoring bounds as defined in the first look above would be applied to this 
second look at SVR.  
 
An unplanned interim review will be triggered if, at any time, more than 20 
persons are not evaluable for the SVR outcome before study discontinuation or 
76 weeks following study enrollment. Another trigger for an unplanned interim 
review is if, at any time, the number of participants experiencing an SAE exceeds 
5% of the interim analysis dataset, and the absolute number of participants with 
SAEs at least 10 (as 5% was the observed upper bound of the 95% CI on 
number of participants with any SAE from the ASTRAL-5 trial).   
 
Any/all SMC reviews will include administrative/trial conduct data as well as 
safety data according to the safety-related outcomes enumerated above. 
 
The following routine monitoring reports are distributed to core team and are 
detailed in the study monitoring plan (SMP): screening, accrual, data 
delinquency, study status, data and sample completeness, with attention to 
evaluation and timing of SVR outcome. The routine safety monitoring report is 
distributed to the DAIDS Clinical Representative and a subset of the core team 
(to include the study chairs) every 3 months. 
 
Further details about monitoring of this study are available in the SMP. 
 
10.6 
Analyses 
 
Due to US federally mandated reporting of outcomes to clinicaltrials.gov, the timing of initiating 
analyses for those outcomes, are likely to occur prior to study follow-up being completed. 
Therefore, there will be separate primary and secondary statistical analyses reports to cover all 
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10.6.1 Primary Efficacy Analysis 
 
The primary efficacy outcome (SVR) will be estimated with a point-wise estimate 
as well as a 95%, two-sided CI. The confidence bound will be calculated with 
binomial distribution according to the method of Wilson (Score based interval). 
The impact of missingness contributing to the (lowering of the) SVR response 
rate will be addressed by providing the various reasons for non-SVR (e.g., 
discontinued treatment early due to various reasons including intolerability, HCV 
RNA > LLOQ, missing evaluation for SVR (and reasons as known), and the 
number of participants meeting each reason for non-SVR. 
 
10.6.2 Primary Safety Analysis 
 
The primary safety outcome of SAEs will be enumerated, summarized and 
described for all qualifying outcomes. The number and relative frequency of 
participants experiencing one or more SAEs will also be summarized, and a CI 
about the probability of experiencing a SAE will be calculated (using CI methods 
as described above).   
 
10.6.3 Secondary Outcomes Analysis 
 
Premature discontinuation of study treatment will be defined from participant self-
report either via remote contact prior to SVR evaluation, or at an unplanned visit 
or by retrospective recall at the week 24 or SVR evaluation visit (whichever 
occurs first). Those participants missing information from all these mechanisms 
will be assumed to have prematurely discontinued. The proportion of premature 
study treatment discontinuation will be estimated and a CI calculated to 
summarize the range of plausible values using methods parallel to other 
dichotomous outcomes described above. 
 
Non-serious AEs will be summarized by the Medical Dictionary of Regulatory 
Affairs (MeDDRA) System Organ Class by the reporting types described in 
section 7.2. 
 
Those who do not achieve SVR with an observed HCV RNA >LLOQ will have 
both baseline and SVR specimens tested for HCV RASs. Participants in this sub-
set with HCV RASs present in their SVR specimen that were not present in their 
baseline specimen will be enumerated along with the relative frequencies of new 
RASs. A description of the observed RASs will also be provided.   
 
Among SVR responders, HCV RNA post SVR follow-up (i.e., Step 2) will be used 
to evaluate for the HCV reinfection outcome. Detectable HCV RNA, with and 
HCV sequence distinct from the baseline sequence will qualify for the outcome of 
HCV reinfection. The absolute number (and relative frequency) of participants 
meeting this outcome will be summarized along with a 95% CI using methods as 
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Among SVR responders, HCV disease regression will be defined by the absolute 
change between baseline FIB-4 value and the final study FIB-4 value. The 
distribution of these absolute changes will also be described using key 
percentiles. 
 
Further details are outlined in the study’s Statistical Analysis Plan (SAP). 
 
11.0 
PHARMACOLOGY PLAN 
 
Not applicable.  
 
12.0  COST-BENEFIT ANALYSIS PLAN 
 
The cost-benefit analysis will employ the resource utilization data collected at 
planned/unplanned study visits until the SVR is assessed (week 24/SVR evaluation visit) 
as well as SVR data and utilization data to develop an estimate of cost/SVR attained. 
 
12.1  Objective 
 
12.1.1  To determine the cost/SVR attained using the MINMON protocol  
 
12.2 
Primary Outcome 
 
12.2.1 Cost/SVR attained - both globally and stratified by country - calculated using 
country-specific costs and expressed in US$ 2017. 
 
12.3 
General Approach to Costing 
 
The cost/SVR attained will be assessed from two perspectives. 
 
12.3.1 
The perspective of the clinic/program/site treating the participant (program 
perspective). These costs include the cost of staff, laboratory monitoring, and 
medications involved in delivering HCV treatment to a participant. These costs 
begin at week 0 and continue through the week 24/SVR evaluation. The 
program cost perspective is helpful to those who administer a clinic or treatment 
program who want to understand how MINMON would impact their program 
budget. 
 
There are two cost components from the program perspective: 
 
1. Cost of HCV medications 
2. Cost of planned and unplanned study visit evaluations between week 0 and 
the week 24/SVR evaluation visit 
 
12.3.2 
The healthcare sector perspective—the health sector perspective is broader 
than the program perspective. It includes the costs of staff, laboratory 
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utilization outside of the study site between weeks 0 and 24, and any changes 
in utilization that may occur in the future as the result of the participant attaining 
SVR.  
 
There are four cost components from the healthcare sector perspective: 
 
1. Cost of HCV medications 
2. Cost of planned and unplanned study visit evaluations between week 0 and 
the week 24/SVR evaluation visit 
3. Cost of healthcare utilization outside of study sites between week 0 and the 
week 24/SVR evaluation visit 
4. Cost saving (or additional cost) that may accrue because a person attains 
SVR and subsequently uses fewer (or more) healthcare resources. This 
cost saving (cost) is defined as the DIFFERENCE in healthcare utilization 
per month measured at the week 48 visit comparted to the week 0 visit. The 
healthcare utilization questionnaire measures utilization over a 4-week 
recall period. This is defined as healthcare utilization per month. The 
difference in healthcare utilization per month between the week 48 
assessment and the week 0 assessment is the monthly savings (or cost) 
attributable to attaining SVR. It will be assumed that the monthly savings 
(cost) applies to every month between week 24 and week 72. 
 
In addition, because this estimate of cost savings is uncertain, sensitivity 
analyses will be used to explore different estimates of saving attained including: 
1) difference in utilization measured at the week 72 visit and the week 0 visit, 2) 
difference in utilization measured at week 72 and week 48 visits. In both of 
these sensitivity analyses, it will be assumed that the monthly savings (or cost) 
we estimate applies to every month between weeks 24 and 72. 
 
Measures of utilization will be translated to cost (expressed in currency rather 
than units of resources consumed) using WHO CHOICE country-specific unit 
costs (http://www.who.int/choice/cost-effectiveness/inputs/health_service/en/). 
 
It will be assumed that all resource utilization between weeks 0 and 24 is 
related to HCV medications. As a result, the cost estimate will tend to be biased 
toward a higher cost/SVR attained. 
 
The primary analysis will be conducted in an intention to treat framework, 
whereby participants who are LTFU and do not return for the week 24/SVR 
evaluation visit are assumed to be treatment failures and not counted as “SVR” 
in the cost/SVR attained calculation. This approach will also tend to bias results 
to a higher cost/SVR attained. A sensitivity analysis will explore cost/SVR when 
it is assumed that the rate of SVR among those lost to follow-up at week 24 is 
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12.4  Resource Utilization Data Collection 
 
12.4.1 
Cost of HCV Medications  
 
We will price HCV therapy by country based on the negotiated price with 
ministries of health. In the U.S., there is no single cost of HCV therapy. For U.S. 
sites, we will price SOF/VEL using the federal supply schedule. Because the 
cost of therapy is dynamic and changes by setting and time, we will use 
sensitivity analyses to explore the impact of drug prices on the cost-benefit of 
treatment.  
 
12.4.2 
Cost of Planned and Unplanned Study Visits  
 
We will consider two components of the cost of a study visit: a) cost of provider 
time, and b) cost of labs and assessments. Cost of the healthcare visits 
(Doctor/physician and staff time)—we will use WHO CHOICE estimates of 
outpatient care delivery costs by country. We will include the week 0 visit (not 
the screening visit as it is a study procedure with no real-world analogue) and 
the visit for week 24/SVR evaluation. In addition, we will include any unplanned 
visits between week 0 and the week 24/SVR evaluation. 
 
We will cost laboratory tests using the national fee schedule for public sector 
healthcare payers in each country. For example, we will use the Center for 
Medicare and Medicaid Services (CMS) reimbursement schedule for laboratory 
test costs in the U.S. and the National Health Laboratory Service schedule for 
sites in South Africa.  
 
12.4.3 
Cost of Healthcare Utilization  
 
To collect healthcare utilization data a questionnaire similar to the ACTG 
Instrument named “ACTG A5265 Resource Utilization Interview” will be used 
following minor adaptation for A5360. 
 
Staff will administer this instrument at the entry visit, the week 24/SVR 
evaluation visit, at the weeks 48 and 72 planned study visits, and at any 
unplanned study visit.  
 
To translate utilization to cost, we will use WHO CHOICE estimates of the cost 
of health care delivery (clinic visits, hospital nights, casualty ward visits) by 
country. 
 
12.5 
Assessing SVR Status 
 
See section 10.2.1 for primary outcome measures. Sensitivity analyses will explore 
cases where non-SVR inferred due to LTFU. 
 


 
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12.6  Estimation of Cost/SVR Outcome 
 
12.6.1 
Program perspective. We will estimate the mean cost per participant including: 
• 
Cost of medications 
• 
Cost of all planned and unplanned study visits between weeks 0 and 
24/SVR evaluation including staff time and laboratory tests 
 
12.6.2 
Healthcare sector perspective 
• 
Cost of medications 
• 
Cost of all planned and unplanned study visits between weeks 0 and 
24/SVR evaluation including staff time and laboratory tests 
• 
Cost of healthcare utilization between weeks 0 and 24/SVR evaluation 
• 
The DIFFERENCE in healthcare utilization as measured at weeks 0 and 48 
 
Cost/SVR attained in each country will be calculated, as well as for the entire study 
population. Cost/SVR both in local currency and in international dollars will be stated. 
The cost/participant who does NOT attain SVR will also be estimated. Sensitivity 
analyses will demonstrate the impact of HCV therapy costs on the cost-benefit of 
MINMON. 
 
In addition, although there is no control arm to which we can compare the cost/SVR 
attained in MINMON, we will estimate the cost/SVR attained for the standard of care 
treatment protocol based on the cost of laboratory tests and medications and the 
planned schedule of events for a standard of care treatment course.  
 
13.0 
DATA COLLECTION AND MONITORING  
 
13.1 
Records to Be Kept 
 
eCRFs will be made available to sites for data entry. Participants must not be identified 
by name on any data submitted to the DMC. Participants will be identified by the patient 
identification number (PID) and study identification number (SID) provided by the ACTG 
DMC upon registration. 
 
13.2 
Role of Data Management 
 
13.2.1 
Instructions concerning entering study data on eCRFs will be provided by the 
ACTG DMC. Each CRS is responsible for keying the data in a timely fashion. 
 
13.2.2 
It is the responsibility of the ACTG DMC to assure the quality of computerized 
data for each ACTG study. This role extends from protocol development to 
generation of the final study databases. 
 


 
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13.3 
Clinical Site Monitoring and Record Availability 
 
13.3.1 
Site monitors under contract to the NIAID will visit participating clinical research 
sites to review the individual participant records, including consent forms, 
eCRFs, supporting data, laboratory specimen records, and medical records 
(physicians’ progress notes, nurses’ notes, individuals’ hospital charts), to 
ensure protection of study participants, compliance with the protocol, and the 
accuracy and completeness of records. The monitors also will inspect sites’ 
regulatory files to ensure that regulatory requirements are being followed and 
sites’ pharmacies to review product storage and management. 
 
13.3.2 
The site investigator will make study documents (e.g., consent forms, drug 
distribution forms, eCRFs) and pertinent hospital or clinic records readily 
available for inspection by the local IRB, the site monitors, the FDA, the NIAID, 
the OHRP, the industry supporter and local, US, and international regulatory 
entities for confirmation of the study data.  
 
14.0 
PARTICIPANTS 
 
14.1 
Institutional Review Board (IRB) Review and Informed Consent 
 
This protocol and the informed consent document (Appendix I) and any subsequent 
modifications will be reviewed and approved by the IRB or ethics committee responsible 
for oversight of the study. A signed consent form will be obtained from the participant (or 
legal guardian, 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 participant, or legal guardian and this fact will be documented in the 
participant’s record. 
 
14.2 
Participant Confidentiality 
 
All laboratory specimens, evaluation forms, reports, and other records that leave the site 
will be identified by coded number only to maintain participant confidentiality. All records 
will be kept locked. All computer entry and networking programs will be done with coded 
numbers only. Clinical information will not be released without written permission of the 
participant, except as necessary for monitoring by the ACTG, IRB/EC, FDA, NIAID, 
OHRP, other local, US, and international regulatory entities as part of their duties, or the 
industry supporter(s) or designee.  
 
14.3 
Study Discontinuation 
 
The study may be discontinued at any time by the ACTG, IRB/EC, FDA, NIAID, OHRP, 
other country-specific government agencies as part of their duties to ensure that 
research participants are protected, or the industry supporter. 
 


 
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15.0 
PUBLICATION OF RESEARCH FINDINGS 
 
Publication of the results of this trial will be governed by ACTG policies. Any 
presentation, abstract, or manuscript will be made available for review by the industry 
supporter prior to submission.  
 
16.0 
BIOHAZARD CONTAINMENT 
 
As the transmission of HIV and other blood-borne pathogens can occur through contact 
with contaminated needles, blood, and blood products, appropriate blood and secretion 
precautions will be employed by all personnel in the drawing of blood, and shipping and 
handling of all specimens for this study, as currently recommended by the Centers for 
Disease Control and Prevention and the National Institutes of Health. 
 
All dangerous goods and materials, including diagnostic specimens and infectious 
substances, must be transported using packaging mandated by CFR 42 Part 72. Please 
refer to instructions detailed in the International Air Transport Association (IATA) 
Dangerous Goods Regulations.  


 
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17.0 
REFERENCES 
 
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2. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of 
hepatitis C virus infection: new estimates of age-specific antibody to HCV 
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3. Ray SC, Bailey JR, Thomas DL. Hepatitis C virus. In: Knipe DM, Howley PM, editors. 
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5. AASLD-IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA 
recommendations for testing, managing, and treating adults infected with hepatitis C 
virus. Hepatology 2015;62(3):932-54. 
6. European Association for the Study of the Liver. Guidelines. EASL Recommendations 
on Treatment of Hepatitis C 2016. J Hepatol 2017;66:153-94. PMID: 27667367. 
7. World Health Organization. Guidelines for the screening, care and treatment of persons 
with hepatitis C infection. April 2014. Available from: 
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8. World Health Organization. New recommendations in the updated WHO guidelines for 
the screening, care and treatment of persons with chronic hepatitis C infection. Policy 
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13. Foster GR, Pianko S, Brown A, et al. Efficacy of sofosbuvir plus ribavirin with or without 
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from the Trio network. Presented at: 66th Annual Meeting of the American Association 
for the Study of Liver Diseases; November 13-17, 2015; San Francisco, CA. 
22. Pol S, Bourliere M, Lucier S, et al. Safety and efficacy of the combination daclatasvir-
sofosbuvir in HCV genotype 1-mono-infected patients from the French observational 
cohort ANRS co22 hepather. [Abstract 44]. Presented at the 50th Annual Meeting of the 
European Association for the Study of the Liver; 22-26 April 2015; Vienna, Austria. 
23. Martinello M, Petoumenos K, Grebely J, et al. Incidence of HCV reinfection among 
treated individuals with recently acquired infection. J Hepatol 2016;64(Suppl):S620-
S621.   
24. McHugh M, Wu A, Pawlotsky J-M, Chevaliez S, Hallin M, Templeton K. Evaluation of the 
Cepheid Xpert® HCV Viral Load Assay. J Clin Virol 2015;70(Suppl 1):S84. 
 
 
 


 
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APPENDIX I: SAMPLE INFORMED CONSENT 
 
 
DIVISION OF AIDS  
 
AIDS CLINICAL TRIALS GROUP (ACTG) 
 
For protocol: A5360 
 
FINAL Version 1.0, 01/10/18: A Single-arm Study to Evaluate the Feasibility and Efficacy of a 
Minimal Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV 
Infected Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The 
MINMON Study 
 
SHORT TITLE FOR THE STUDY: A5360 FINAL Version 1.0, 01/10/18, Monitoring SOF/VEL in 
Treatment Naïve, HCV Participants with Active Infection 
 
INTRODUCTION 
 
 
You are being asked to take part in this research study because you have been infected with 
hepatitis C virus (HCV, a virus that affects the liver), and have not been treated before for HCV. 
You may also be infected with human immunodeficiency virus (HIV, the virus that causes AIDS). 
You may have compensated liver cirrhosis, which means that the liver is damaged, but is still 
working. This study is sponsored by the National Institutes of Health. The doctor in charge of 
this study at this site is: (insert name of Principal Investigator). Before you decide if you want to 
be a part of this study, we want you to know about the study.  
 
This is a consent form. It gives you information about this study. The study staff will talk with you 
about this information. You are free to ask questions about this study at any time. If you agree to 
take part in this study, you will be asked to sign this consent form. You will get a copy to keep. 
 
 
WHY IS THIS STUDY BEING DONE? 
 
Currently, people who are infected with HCV are often closely monitored by medical staff. This 
requires patients to come to the clinic at least five times for visits, medication refills, and blood 
tests over a 12-week course of treatment. These guidelines are based on older HCV 
medications that had more side effects and were less successful at curing HCV than the 
medications used in this study. New HCV medications can cure 95 out of 100 infected persons 
who receive treatment. The medication that is provided in this study is approved by the US FDA 
for use in persons infected with HCV and coinfected with HCV/HIV. In large clinical trials, the 
side effects reported by study participants were comparable to a placebo (no medicine).   
  
This study is being done to see if a minimal monitoring approach is effective and safe when 
providing HCV treatment. The minimal monitoring approach will require fewer study visits and 
lab tests with no medication refills. This study is trying to see whether taking an HCV treatment 
with fewer clinic visits and laboratory tests can cure just as many people as the standard 
approach that uses more visits and laboratory tests. We will compare the results of this study 
with what we have observed in other studies using a standard approach. 
 


 
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People are considered cured of HCV if the HCV virus cannot be detected in the blood 12 weeks 
after they have completed HCV treatment. This is called a sustained virologic response (SVR).  
 
This study will measure the amount of HCV virus in your blood at entry, week 24, week 48, and 
week 72. The study staff will share these results with you. If the HCV virus is detectable in your 
blood at week 24 or after, the study staff will let you know, and help you find a health care 
provider who can discuss your future treatment options. You can become re-infected with HCV 
after you are cured. The study staff will discuss with you how to remain HCV free after your 
treatment is completed.  
 
The study will also examine the convenience to you and the cost to cure a person of HCV using 
this minimal approach. 
 
 
HOW MANY PEOPLE WILL BE IN THIS STUDY? 
 
About 400 people (men and women age 18 years and older) will take part in this study. 
 
 
WHERE IS THIS STUDY BEING DONE? 
 
This study will take place across the world and will include participants from the US and non-US 
sites. 
 
 
HOW LONG WILL I BE IN THIS STUDY? 
 
You will be in this study for up to 72 weeks.  
 
 
WHAT DO I HAVE TO DO IF I AM IN THIS STUDY? 
 
If you decide to join this study and meet the study requirements after the screening visit, you will 
be enrolled into the study, unless enrollment has been closed to the subgroup(s) as described 
below.   
 
Individuals with HIV infection and/or have compensated cirrhosis (liver is damaged but it is still 
working) are also eligible for the study. Enrollment, however, of HIV-infected individuals or those 
with compensated cirrhosis will be limited in the study (i.e., only a certain number of persons will 
be included in the HIV-infected subgroup and compensated cirrhosis subgroup). The study staff 
will let you know if this limit has been reached for either subgroup, and what this means for you.  
 
At the entry visit, you will be given your study medication for all 3 months to take home. You will 
need to store the medication in a safe place at room temperature (below 30°C [86ºF]) and take 
one tablet a day for the 3-month period.  
 


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*After a person has successfully completed treatment for HCV, there is a period when HCV viral 
load in the blood is so low that even the most sensitive test cannot detect the virus. If this period 
of “undetectability” lasts for 12 weeks in a row after the end of treatment, it is called SVR 
(sustained virologic response). 
 
Everyone who enters the study will take a fixed-dose combination of sofosbuvir/velpatasvir 
(SOF/VEL), which will be provided by the study. Anti-HIV drugs will not be provided by the 
study.  
 
While you are in this study, you will need to be seen in the clinic about 5 times. The longest visit, 
which will be your enrollment visit, could take up to 2 hours. Study staff will tell you about how 
long each visit will be. You may need to come to the clinic more often if you have side effects. 
More information about the study tests is given below. During the study, you will get the results 
from any routine tests that are done during the study and relevant to your care when they are 
available.  
 
If you do not enroll into the study 
If you decide not to take part in this study or if you do not qualify to take part in this study, we 
will still use some of your information. As part of the screening visit, some demographic (for 
example, age, sex, gender, race), clinical (for example, disease condition, diagnosis), and 
laboratory (for example, CD4+ T-cell count, HCV and HIV viral load) information is being 
collected from you so that ACTG researchers may see if there are patterns or common reasons 
why people do not join a study. 
 
Required Blood Tests 
Your blood will be drawn from a vein in your arm and used to measure your HCV viral load (the 
amount of HCV virus in your blood), to measure levels of certain hormones (chemical 
messengers in your blood), to see if the hepatitis B virus (HBV; another virus that affects your 
liver) is in your body, and for routine safety tests and metabolic tests (to test how your body 
uses the food that you eat). If you are a woman able to become pregnant, you will have a 
pregnancy test at the screening and entry visits and at later study visits if you think you might be 
pregnant. If you are infected with HIV, you will have blood drawn to measure your HIV viral load 
(the amount of HIV virus in your blood) and your CD4+ cell counts (these are cells in your blood 
that fight infection). You will be told the results of these tests when they become available.  
 
Some of your blood will also be stored (with no information that will identify you) and used for 
HCV genotyping (a test to see the genetic makeup of the HCV virus) and sequencing (a test to 
check for the pattern/code of the genetic makeup of the HCV virus) for this study. HCV 
genotyping and sequencing are used to see which genotype of HCV you are infected with. 
Since these stored samples will be tested in the future, the results will not be available to you. 
 
Blood will also be collected and stored for future testing at the end of the study. Some of your 
blood samples may be shipped and/or stored outside of the country from which they are 
collected. 
 


 
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Genetic (the message in your DNA) testing 
If you agree, your blood will be drawn and used to examine different genes (pieces of your 
DNA). Results of testing done on these samples may not be given to you because they will be 
done in the future. If you do not agree to have genetic testing done, then the amount of blood 
drawn for future testing will be less (up to 20 mL less).  
 
Please initial below if you agree to have any of your blood used for ACTG-approved future 
unspecified genetic testing. You may change your mind at any time and your samples will be 
destroyed.  
________ YES                     ________ NO 
 
Optional Tests 
If you agree, any blood left over after all required study testing is done may be stored (with no 
information that will identify you) and used for future ACTG-approved research. These blood 
samples may be stored for an unknown period of time. Results of testing done on these 
samples may not be given to you because they will be done in the future. 
 
Please initial below if you agree to have any of your leftover blood used for future ACTG-
approved research. You may change your mind at any time and reasonable efforts will be made 
to destroy your samples, though this may not always be possible.  
 
________ YES                     ________ NO 
 
A5360 Study Visits 
 
The study staff can answer any questions you have about individual study visits, the evaluations 
that will occur, or how long each visit will be. The table below can be used as a quick reference 
for you, along with the explanations that follow. 
 
I. Appendix Table 1: Study Schedule 
 
Evaluation or 
test 
Scre
enin
g 
Entry 
Post-Entry Visits 
Unplanned 
Visits 
(Entry-
Week 24) 
Week 
4 
Week 
22 
Week 
24/SVR 
Evaluati
on 
Week 
42 
Week 
48 
Week 
68 
Week 
72 
Consent & 
Contact 
Information 
Collected 
 
 
 
 
 
 
 
 
 
 
Documentation 
of HCV, HIV, & 
Cirrhosis Status  
 
 
 
 
 
 
 
 
 
 
Liver 
Elastography (if 
available) 
 
 
 
 
 
 
 
 
 
 


 
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Evaluation or 
test 
Scre
enin
g 
Entry 
Post-Entry Visits 
Unplanned 
Visits 
(Entry-
Week 24) 
Week 
4 
Week 
22 
Week 
24/SVR 
Evaluati
on 
Week 
42 
Week 
48 
Week 
68 
Week 
72 
Physical Exam 
 
 
 
 
 
 
 
 
 
(if 
indicated) 
Medical & 
Medication 
History 
 
 
 
 
 
 
 
 
 
 
Blood Samples 
Collected (for 
laboratory 
testing) 
 
 
 
 
 
 
 
 
 
(if 
indicated) 
Blood Samples 
Stored (for later 
testing) 
 
 
 
 
 
 
 
 
 
(if 
indicated) 
Pregnancy Test  
 
 
 
 
(if 
suspecte
d) 
 
 
 
 
(if 
suspected) 
Pregnancy 
Prevention 
Counseling 
 
 
 
 
 
 
 
 
 
 
Cirrhosis 
Counseling 
 
 
 
 
 
 
 
 
 
 
HCV Risk-
reduction 
Counseling 
 
 
 
 
 
 
 
 
 
 
Adherence 
Counseling 
 
 
 
 
 
 
 
 
 
 
Questionnaires 
 
 
(via 
remote 
contact
) 
 
 
 
 
 
 
 
Study Drugs 
Distribution  
 
 
 
 
 
 
 
 
 
 
Locator 
Information 
 
 
 
 
 
 
 
 
 
 
Remote 
Contact With 
Participants 
Outside of 
Study Visits 
 
 
 
 
 
 
 
 
 
 
 


 
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II.  
Description of Study Visits 
 
Screening 
After you have read and signed the consent form, you will be asked questions about 
your health, medical history, and medication history. You will have a complete physical 
exam to check your vitals (temperature, pulse, respiration rate, and blood pressure) and 
several tests, including blood tests, to make sure that you qualify to join the study. You 
will have your height and weight recorded. 
 
Up to 42 mL of blood will be drawn during this visit. You will have blood drawn for HCV 
RNA testing. Some of the blood taken will be shipped to a testing lab and some of the 
blood will be stored for future testing. Your HCV infection and how long you have been 
infected will be confirmed. Your HIV infection and cirrhosis status will also be evaluated. 
 
If you are a woman able to become pregnant, you will have a blood draw or urine 
collected for pregnancy testing. You may not continue with the screening process if your 
pregnancy test is positive. If you are able to become pregnant or to impregnate a 
partner, you will receive pregnancy prevention counseling.  
 
Entry 
If all of the results from your screening tests show that you are eligible, you will be 
enrolled in the study. You will be asked about your health and the medications you are 
taking. You will also have a brief physical exam to check your vitals (temperature, pulse, 
respiration rate, and blood pressure). You will have your weight recorded.  
 
Up to 51 mL of blood will be drawn during this visit. You will also have additional 
samples collected and stored for later testing. If you are a woman able to become 
pregnant, you will be asked to provide a blood or urine sample for pregnancy testing. 
You may not enroll in the study if your pregnancy test result is positive.  
 
If available at the site, liver elastography (scan of your liver) will be performed. This is 
described below in more detail. If you had a liver elastography done as part of standard 
care, this measurement will be recorded but it is not required for enrollment into the 
study.   
 
You will be asked for your primary preferred contact information as well as a second 
contact (spouse, friend, neighbor, etc.) in order for the study staff to reach you 
throughout the study. This is known as locator information. If you are not able to be 
reached through the primary contact information, then the study staff will try to reach you 
through the second contact you provide.  
 
At this visit, you will be given your study drugs. The study staff will give you enough 
study drugs to last 12 weeks (3 months). Study staff will watch you take your first dose 
before leaving the site. You can take the study medication (SOF/VEL) with or without 
food. You will receive adherence education and counseling on the study drug, as 
described below. You will be given instructions on how to take the study medication and 
what to do if you forget to take it. You will also receive a flier with information on two 


 
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types of other medications (proton pump inhibitors and H2 inhibitors [e.g., heartburn 
medication]) that you should not take while taking study medication. [Sites: Please 
include local names of PPIs and H2 inhibitors on a flyer to give to participants at entry. 
Pictures should also be included on the flyer.] 
 
You will be asked to complete questionnaires that asks how you are doing and feeling, if 
you went to the hospital within the past 4 weeks, and if you use any substances such as 
alcohol, cigarettes, and other drugs. If you have compensated cirrhosis, you will also 
receive counseling for your cirrhosis, as described below. If you are able to become 
pregnant or to impregnate a partner, you will receive pregnancy prevention counseling. 
You will also receive HCV risk-reduction counseling and adherence counseling, as 
described below.  
 
Post-entry visits 
Since you will be given enough study drugs to last you for 12 weeks of the treatment 
period, you will not need to come back to the clinic until week 24 (3 months later). Study 
staff will contact you by the preferred contact at weeks 4 and 22 to update your contact 
(locator) information and at week 4, to collect information about whether you are taking 
your study medication. If study staff are unable to reach you after two tries, they will try 
to reach you via your second contact. While you are taking the study drug, if you are not 
feeling well or have any questions about the study medication, you should contact the 
study site directly at (Site to insert site contact information: Name- Number-). 
 
All participants will be seen post-treatment at week 24. If you miss the week 24 visit, you 
may come back to the site to have your SVR status checked any time after week 24, up 
until week 72. Following your SVR status check, you will be followed through week 72. 
You will need to make two more visits to the site -- one at week 48 and one at week 72, 
which is Part 2 of the study. These visits will last about 1-1½ hours each. 
 
At the week 4 remote contact, you will be asked how you are doing with taking your 
study medication. At the week 24/SVR evaluation visit, you will be asked how you did 
with taking your study medication.  
 
At weeks 24, 48, and 72, you will have blood samples collected for routine safety tests 
and for a few required blood tests (HCV RNA). Up to 76 mL of blood will be drawn during 
each of these visits. You will also have additional samples collected and stored for later 
testing. You will be asked about your health and any changes in your medicines since 
your last visit. You will have your weight recorded. You will be asked to complete 
questionnaires that asks how you are doing and feeling, if you went to the hospital within 
the past 4 weeks, and if you use any substances such as alcohol, cigarettes, and other 
drugs. 
 
Based on other tests done, the study staff will calculate different scores that will measure 
liver and kidney function and cirrhosis status. If you have compensated cirrhosis, you will 
also receive counseling for your cirrhosis, as described below. 
 


 
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If available at the study site where you were enrolled, you will have a liver elastography 
done at weeks 24, 48, and 72.  
 
You will receive HCV risk-reduction counseling, as described below. If you have 
compensated cirrhosis, you will also receive counseling for your cirrhosis, as described 
below.   
 
Unplanned visits 
If you have any side effects during the treatment period, you must contact the study site. 
The study staff may require you to come in to the study site for an in-person evaluation. 
It is possible samples are collected for routine safety laboratory tests, or stored for future 
testing. If suspected, pregnancy testing and counseling will be done up to week 22. Up 
to 52 mL of blood could be drawn during this visit. 
 
If you come to the study site for an unplanned visit, you will be asked to complete 
questionnaires that asks how you are doing and feeling, and if you went to the hospital 
within the past 4 weeks. 
 
 
Early discontinuation 
There are two types of discontinuation (stopping study treatment or leaving the study 
early). If at any point in the study, you want to discontinue study treatment or discontinue 
the study, you must contact the site immediately.  
 
1. Stop study treatment early 
 
You or your doctor may decide to stop the study medication that you began at entry. 
 
If you must stop taking the study medication early, the study doctor may ask you to 
stay in the study and come in for the scheduled visits and tests. 
 
2. Leave study early 
 
You or your doctor decides that you will no longer stay in the study or you are 
notified the study is stopped early.  
 
III. 
Description of Study Evaluations 
 
Consent and contact information collected 
After you read the consent form and have had a chance to ask questions about the 
study, you will sign the consent form if you want to continue the screening process. 
 
Documentation of HCV, HIV, and cirrhosis status 
Study staff will check your medical records for the availability of test results for HCV, 
HIV, and cirrhosis. If these results are not available, then you will have these tests done 
as part of the screening visit.    
 


 
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Liver Elastography 
At entry, a liver elastography measurement (if available) will be recorded. A liver 
elastography is an easy, simple, and safe ultrasound procedure that measures the 
stiffness of the liver by placing a small probe over the area of the liver while you lie on 
your back.  
 
Clinical Assessments 
You will have the following clinical evaluations in this study: 
 
Physical examination 
You will have a physical exam. At screening, the study staff will check the different areas 
of your body such as head, neck, eyes, ears, nose, throat, mouth and tongue, chest 
(excluding breasts), heart, abdomen, skin, hair, nails, and muscles and joints. The study 
staff will also check your vital signs such as temperature, pulse, blood pressure, and 
respiratory rate. Your height and weight will be recorded. After screening, the physical 
exam will be more limited and based on symptoms or problems that you are 
experiencing. Your weight will be recorded. 
 
Medical and medication history 
You will be asked questions about your health and about any medicines you have taken 
or are taking now. At week 24/SVR evaluation visit, you will be asked about any signs or 
symptoms that you are experiencing and any changes in other medications that you 
have had since your last visit.  
 
Sample collections and laboratory testing 
You will have the following samples collected and tested in this study: 
 
Blood collected 
Blood will be taken from a vein in your arm for various tests during the study.   
 
Stored blood 
Additional blood will also be collected from you and stored for testing at the end of the 
study. 
 
Pregnancy test 
If you are a woman who is able to become pregnant, you will have blood or urine taken 
for pregnancy testing at screening and entry. After you enter the study, you will have 
blood drawn or urine collected for pregnancy testing, if pregnancy is suspected up to 
week 22. 
 
Pregnancy prevention counseling 
All participants in the sexually reproductive age group will be counseled on family 
planning options for the duration of treatment (12 weeks). There is limited data on the 
safety of this medication during pregnancy and risk to the baby. Female participants who 
become pregnant during the course of treatment will be required to contact the site 
immediately and come in for a study visit as soon as possible. 
 


 
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Cirrhosis Counseling 
If you have compensated cirrhosis, you will be counseled by study staff on managing 
your cirrhosis. Even though you may be cured of HCV, you will still have cirrhosis.  
 
HCV Risk-reduction Counseling 
You will be counseled by study staff on how HCV can be passed onto others and how to 
reduce your risk for HCV reinfection. HCV risk-reduction counseling will be done at 
entry, and weeks 24/SVR evaluation, 48, and 72. Study staff will talk with you about how 
you could become reinfected with HCV after being cured and ways to decrease risk of 
re-infection. 
 
Adherence Counseling 
You will get some adherence counseling from the study staff. The study staff will explain 
to you in detail how to take your study medication and help you find ways to take the 
medication correctly. 
 
Questionnaires 
You will be asked to complete a questionnaire that will ask how you are feeling and how 
you are doing with your daily activities. If you had stayed at a hospital or been to an 
emergency room, you will be asked to complete a questionnaire when you come in for 
your visits at entry, weeks 24/SVR evaluation, 48, 72, and unplanned visits (if any). You 
will also be asked about substance use such as alcohol, cigarettes, and other drugs at 
your entry and weeks 24/SVR evaluation, 48, and 72 visits.  
 
See remote contact section below for information on what questions will be asked during 
the week 4 and 22 remote contacts. 
 
Study drugs distribution and storage 
You will be given a 12-week supply of study medication at entry. Study staff will watch 
you take your first dose, before you leave the site. You will be asked to store the study 
medication as instructed on the medicine bottle label.  
 
If you lose your study medication, you will be able to return to the site and receive 
replacement medication (one-time replacement only). 
 
Locator Information 
Study staff will ask you about the best way to reach you when they need to contact you 
remotely at weeks 4, 22, 42, and 68. They will also ask you for a second way to contact 
you (for example, through a spouse or friend) if they are unable to reach you.  
 
Remote contact with participants outside of study visits 
Study staff will contact you using your preferred method at week 4 to ask questions 
about adherence information (if you are taking your study drug), to update your contact 
information, and to remind you to return to the site to have your SVR status checked at 
week 24. 
 


 
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During Part 1 of the study while you are taking the study (HCV) medication, you will be 
asked at week 4 if you are currently taking your study medication.  
 
At week 22, study staff will contact you to schedule your week 24 visit to have your SVR 
status checked and to update your contact information.  
 
During Part 2 of the study, after the week 24 visit, you will be contacted using your 
preferred remote method at weeks 42 and 68 to update contact information, if needed, 
and remind you of your upcoming study visits at weeks 48 and 72.  
 
 
WHY WOULD THE DOCTOR TAKE ME OFF THIS STUDY EARLY? 
 
The study doctor may need to take you off the study early without your permission if: 
 
• 
The study is cancelled. 
• 
Your doctor thinks the study is no longer in your best interest. 
• 
The site investigator thinks that you are at significant risk of failing to comply with the 
requirements of the protocol.  
 
The study doctor may also need to take you off the study drugs without your permission if: 
 
• 
You become pregnant. 
• 
You are breastfeeding. 
• 
Continuing the study drugs may be harmful to you. 
• 
You need a treatment that you may not take while on the study. 
 
If I have to permanently stop taking study drugs through the study, or once I leave the study, 
how can I get study drugs? 
 
If you must permanently stop taking SOF/VEL before the study is over, the study staff will talk 
with you about other options. 
 
After you have finished the study, you will not be able to get SOF/VEL through the study. 
 
 
WHAT ARE THE RISKS OF THE STUDY? 
 
Risks of Social Harm 
Although the study site will make every effort to protect your privacy and confidentiality, it is 
possible that others could find out that you are participating in this study and that social harm 
may result (because you could become labeled as being infected with HCV and/or HIV). For 
example, you could be treated unfairly or discriminated against by family members, friends, 
and/or the community. 
 


 
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Risks of Drawing Blood 
Drawing blood may cause some discomfort, lightheadedness, bleeding, swelling, or bruising 
where the needle enters the body, and in rare cases, fainting, or infection. 
 
Risks of Study Drug 
The study drug (SOF/VEL) is relatively safe and in controlled clinical trials it was found to have a 
safety profile similar to a placebo (no medicine). The most common side effects you may 
experience are headache, nausea, vomiting, fatigue and diarrhea.  
 
SOF/VEL has limited drug interactions with HIV medications with the exception of three HIV 
medications- efavirenz, tenofovir, and tipranavir/ritonavir. If you are taking any of these 
medications, your doctor will talk to you about these interactions in detail and what symptoms to 
look out for. Your doctor may modify your HIV medications after discussing it with you so that 
you can be included in this study.  
 
SOF/VEL also has some interactions with other types of medications. There is risk of slow 
heartbeat if you also take amiodarone (a medication to help control heart rate). While you are on 
the study, you will be instructed not to take any of the prohibited medications (for example, 
heartburn medication mentioned earlier). The study staff will explain the prohibited and 
precautionary medications and discuss alternative options if you must take any of these 
concomitant medications.   
 
There is a risk of serious and/or life-threatening side effects when non-study medications are 
taken with the study drugs. For your safety, you must tell the study doctor or nurse about all 
medications you are taking before you start the study and also before starting any new 
medications while on the study. Also, you must tell the study doctor or nurse before enrolling in 
any other clinical trials while on this study. 
 
Other Risks 
There is a risk that your stored samples may be misused. There are laws against this kind of 
misuse, but they may not fully protect you. The chance that this will happen is considered small 
because of the security taken with your samples.  
 
Your genetic information is unique to you. There is a risk in genetic research that someone 
using your samples may identify you. However, this risk is very small, but may increase with the 
progress of science. Researchers will inform you of any newly identified risks. 
 
If you are cured of your HCV, you could still become infected again with HCV. You can get HCV 
from coming in contact with blood and/or sexual fluid that is infected with HCV. 
 
 
ARE THERE RISKS RELATED TO DELAYING HIV THERAPY? 
 
You are not required to be on HIV medications to enter this study. If you are not on HIV 
medications at the time of your HCV infection and you and your doctor do not think you need to 
start HIV medications, we will not exclude you from the study. We also do not recommend 
delaying HIV medications for entry into the study if your doctor feels they are medically 


 
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necessary. Although the dosing period of the HCV medication is short (84 days), a delay in 
necessary HIV medications could allow for progression of HIV disease, which can increase your 
risk of opportunistic infections and long-term after effects of HIV infection. If you have any 
concerns about these risks, we suggest that you discuss them with your medical provider. 
 
 
ARE THERE RISKS RELATED TO PREGNANCY? 
 
The drugs or drug combinations in this study have not been studied extensively in pregnancy. If 
you are having sex that could lead to pregnancy, you must agree not to become pregnant or to 
impregnate your partner while you are taking the study medication and for 6 weeks after 
stopping study medication. Note that if you become pregnant, study drug will be stopped and 
you will be asked to remain on the study. If you think you may be pregnant at any time during 
the study, tell your study staff right away. Pregnancies occurring on study will be reported to the 
Antiretroviral Pregnancy Registry, and study staff will request permission from you to obtain 
additional information after the baby is born. 
 
Because of the risk involved, you must use at least one method of birth control that you discuss 
with the study staff. You must continue to use at least one method as long as you are taking 
study medication and for 6 weeks after stopping study medication. You must agree to one or 
more of the birth control methods listed below: 
• 
A condom (male or female) with or without a spermicide 
• 
Diaphragm or cervical cap with or without spermicide 
• 
An intrauterine device (IUD) 
• 
Tubal ligation 
• 
Hormone-based contraceptives  
 
Male and female participants not of reproductive potential are not required to use 
contraceptives. 
 
Some of the methods listed above may not prevent the spread of HIV to other people. If you are 
also infected with HIV, you should discuss your contraceptive choices with your health care 
provider to choose the best way for you to both prevent pregnancy as required by this study and 
to prevent the spread of HIV to your partner.  
 
Male participants should not donate sperm while on study treatment and for six weeks after 
stopping study medication. 
 
 
ARE THERE BENEFITS TO TAKING PART IN THIS STUDY? 
 
If you take part in this study, there may be a direct benefit to you. The study is designed to treat 
your HCV infection with an approved study medication and you may be cured of your HCV. It is 
also possible that you may receive no benefit from being in this study. Information learned from 
this study may help others who have HCV and/or HIV. 
 


 
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WHAT OTHER CHOICES DO I HAVE BESIDES THIS STUDY? 
 
Instead of being in this study, you have the choice of: 
• 
treatment with prescription drugs currently available to you 
• 
treatment with other experimental drugs, if you qualify  
• 
no treatment 
 
Please talk to your doctor about these and other treatment choices available to you and the 
risks and benefits of these choices. 
 
 
WHAT ABOUT CONFIDENTIALITY? 
 
For Sites in the US 
 
We will do everything we can to protect your privacy. In addition to the efforts of the study staff 
to help keep your personal information private, we have gotten a Certificate of Confidentiality 
from the US Federal Government. This certificate means that researchers cannot be forced to 
tell people who are not connected with this study, such as the court system, about your 
participation. Also, any publication of this study will not use your name or identify you 
personally.   
 
Your records may be reviewed by the US Food and Drug Administration (FDA), the ACTG, the 
US Office for Human Research Protections (OHRP), or other local, US, and international 
regulatory entities as part of their duties (insert name of site) institutional review board (IRB) (a 
committee that protects the rights and safety of participants in research), National Institutes of 
Health (NIH), study staff, study monitors, drug companies supporting this study, and their 
designees. Having a Certificate of Confidentiality does not prevent you from releasing 
information about yourself and your participation in the study. 
 
Even with the Certificate of Confidentiality, if the study staff learns of possible child abuse and/or 
neglect or a risk of harm to yourself or others, we will be required to tell the proper authorities. 
 
A description of this clinical trial will be available on ClinicalTrials.gov, as required by U.S. law. 
This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time.  
 
For Sites outside the US 
 
Efforts will be made to keep your personal information confidential. We cannot guarantee 
absolute confidentiality. Your personal information may be disclosed if required by law. Any 
publication of this study will not use your name or identify you personally. 
 
Your records may be reviewed by the US FDA, the ACTG, the US Office for Human Research 
Protections (OHRP), or other local, US, and international regulatory entities as part of their 
duties, (insert name of site) institutional review board (IRB) or Ethics Committee (a committee 


 
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that protects the rights and safety of participants in research), National Institutes of Health 
(NIH), study staff, study monitors, drug companies supporting this study, and their designees.  
 
A description of this clinical trial will be available on ClinicalTrials.gov, as required by US law. 
This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time.  
 
WHAT ARE THE COSTS TO ME? 
 
There will be no cost to you for the study drugs, the study visits, physical examinations, 
laboratory tests or other tests required by the study. You or your insurance company, or your 
health care system will be responsible for the costs of your regular medical care as well as for 
the costs of drugs not given by the study.  
 
 
WILL I RECEIVE ANY PAYMENT? 
 
[Sites: Please indicate whether you will provide payment to participants. If so, please describe 
the amount to be paid or reimbursed, the payment schedule, and any prorated schedule should 
the participant decide to withdraw or is withdrawn early by the investigator. Please also include 
a value to be used as an incentive (as justified by your IRB) for attending the SVR visit, as 
determined appropriate according to site location.] 
 
 
WHAT HAPPENS IF I AM INJURED? 
 
If you are injured as a result of taking part in this study, you will be given treatment right away 
for your injuries and be referred for further treatment, if necessary. However, you or your 
insurance company may have to pay for this care. There is no program for compensation, either 
through this institution or the NIH. You will not be giving up any of your legal rights by signing 
this consent form. 
 
 
WHAT ARE MY RIGHTS AS A RESEARCH PARTICIPANT? 
 
Taking part in this study is completely voluntary. You may choose not to take part in this study 
or leave this study at any time. The care that you would normally receive will not be affected if 
you decide not to take part. Your decision will not affect other studies done by NIH in which you 
may be taking part, and will not lead to any penalty or loss of benefits that you have the right to 
expect.   
 
We will tell you about new information from this or other studies that may affect your health, 
welfare, or decision to stay in this study. If you want the results of the study, let the study staff 
know. 
 
 
WHAT DO I DO IF I HAVE QUESTIONS OR PROBLEMS? 


 
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For questions about this study or a research-related injury, contact: 
 
• 
name of the investigator or other study staff 
• 
telephone number of above  
 
For questions about your rights as a research participant, contact: 
 
• 
name or title of person on the Institutional Review Board (IRB) or other organization 
appropriate for the site 
• 
telephone number of above 


 
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SIGNATURE PAGE ACTG Study A5360 
 
If you have read this consent form (or had it explained to you), all your questions have been 
answered and you agree to take part in this study, please sign your name below. 
 
 
 
____________________________ 
 
_________________________________________ 
Participant’s Name (print) 
 
Participant’s Signature and Date 
 
 
____________________________ 
________________________________________ 
Participant’s Legal Representative’s 
Legal Representative’s Signature and Date 
Name (print) (As appropriate) 
 
 
____________________________ 
 
_________________________________________ 
Study Staff Conducting 
 
Study Staff’s Signature and Date 
Consent Discussion (print)  
 
 
____________________________ 
 
_________________________________________ 
Witness’s Name (print) 
 
Witness’s Signature and Date 
(As appropriate)