Clinical trial NCT03987503
Conditions: Hepatitis C, Chronic
Keywords: People who inject drugs Homeless Community-based testing and treatment
Sponsor: University of California, San Francisco
Start date: 2020-07-01; Completion date: 2022-12-29
Enrollment: 87 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) offers a cure to those with chronic HCV infection. For marginalized communities, linkage to care services often aren't enough to overcome barriers to accessing the medical system. For difficult to link populations, offering treatment at the same non-clinical community space may improve uptake and reduce loss-to-follow-up. The purpose of this 2 year study is to assess the feasibility, acceptability and effectiveness of accelerated initiation of commercially available DAA therapy targeting socially marginalized communities (e.g., medically underserved, homeless, people actively injecting drugs). The study will be carried out at two community sites that perform HCV testing: (a) fixed community site and (b) community mobile site via clinical research van. Participants (n=150) who test anti-HCV positive and HCV RNA positive (chronic infection) are invited to enroll into the no one waits (NOW) Study and begin HCV treatment at point of diagnosis. All evaluation, medication dissemination, and follow-up care will take place at the project site. The investigators will estimate the effect of on-site point-of-diagnosis (POD) treatment on (1) time from HCV testing to treatment initiation, (2) completing treatment, and (3) attaining (sustained virologic response) SVR-12; overall and by study site. A secondary product will be a lesson learned guide of recommendations for implementing a POD on-site test and treat program for dissemination beyond San Francisco.

Detailed description:
This study is a non-randomized interventional study.

NOW is an open-label study evaluating the feasibility, acceptability, and effectiveness of an accelerated community-based treatment program of SOF/VEL x 12 weeks started at time of chronic HCV diagnosis (intervention).

The purpose of the proposed study is to assess the feasibility, acceptability and effectiveness of accelerated initiation of commercially available direct-acting antiviral (DAA) therapy targeting socially marginalized communities (e.g., medically underserved, homeless, people actively injecting drugs). The proposed study will be carried out at two community sites that perform HCV testing: (a) fixed community site and (b) community mobile site. The fixed site is located in the Tenderloin Neighborhood of San Francisco: The Quaker Meeting House (QMH). The QMH is the current location for an established drop-in center for young adult (\< 30 years old) people who inject drugs, a group at highest risk for acquiring new HCV infection but representing a group with the lowest engagement in HCV treatment. The QMH site is complete with two phlebotomy stations, centrifuge, clinical exam station, interview rooms, and office space. The QMH research site will prioritize study enrollment for young adult people who inject drugs (PWID). The community mobile site (DeLIVER Van) is situated in a mobile van; a 145 sqft space equipped with a phlebotomy station, clinical exam table, centrifuge, and portable Fibroscan® 430 Mini Plus. The DeLIVER Van will serve two neighborhoods in San Francisco with high HCV burden but few community-based medical service organizations: the Bayview neighborhood and Outer Mission neighborhood.

The investigators will (1) implement new tools, notably FIBROSCANS, to measure fibrosis in an at-risk group (HCV positive patients); (2) implement a new standard of care, treatment on-demand in an at-risk group (HCV positive active drug users); (3) assess the feasibility and acceptability of expanding standard of care into non-clinical settings.

At study entry, participants will undergo a combined eligibility screening/entry visit, which includes HCV testing (antibody and RNA), rapid anti-HIV test, and HBsAG (hepatitis B virus surface antigen) testing and consent for medical record linkage. If HCV RNA reactive, participants are offered enrollment into the treatment cohort and provided 2 week supply of SOF/VEL (provided by Gilead as part of the NOW Study) upon completion of a clinical evaluation, baseline survey, and venipuncture for baseline labs. If the participant is actively insured, the study investigators will obtain insurance-authorized SOF/VEL to complete the remainder of the 12 week treatment course. If the participant is not actively insured, the study team will assist with insurance acquisition and subsequently obtain insurance-authorized SOF/VEL to complete the remainder of the 12 week treatment course. For any participants, if insurance-authorized SOF/VEL is delayed beyond the initial 2 week study-provided SOF/VEL, additional supplies of SOF/VEL as needed to ensure an uninterrupted 12 week treatment course. Participants will return every 2 weeks during treatment (12 week course) for medication dispensation and study visit activities. And for two post-treatment visits for clinical monitoring (e.g., HCV RNA testing) and research activities.

Study participants in the intervention study (cohort): Chronic HCV (anti-HCV positive and HCV RNA positive) men and women ages ≥18 years newly diagnosed or re-engaged in care at a fixed or mobile community-based site. Participants should be HBsAg negative, have no known history of decompensated cirrhosis or end stage renal disease, not be pregnant or breastfeeding, and not be taking medications that are contraindicated with SOF/VEL.

Arms: arm 1: At the point of HCV infection diagnosis, (HCV RNA positive and anti-HCV positive) individuals who meet eligibility criteria and elect to start HCV treatment at the same visit and monitored at two-week intervals at the community-site. arm 2: Participants who test positive for HCV chronic infection (HCV RNA positive, and anti-HCV positive) but elect to not enroll in the intervention arm. Electronic medical record data will be reviewed for up to 2 years for HCV related care information (e.g., HCV treatment start date, end date, SVR-12).
Interventions: intervention 1: Epclusa (SOF/VEL) intervention 2: Standard of care intervention 3: Fibroscan® 430 Mini Plus
Intervention descriptions: intervention 1: a trained physician will provide research participants with two-week supply of SOF/VEL. Treatment is: 1 tablet SOF/VEL (400 mg sofosbuvir/100 mg velpatasvir) daily x 12 weeks. The initial 2-week supply is provided by Gilead Sciences and will be dispensed to participants upon enrollment. Prescriptions and insurance prior authorizations for SOF/VEL will be submitted by the study pharmacist though the UCSF Specialty Pharmacy. The study team will be notified once insurance-authorized drug is available and will bring participants' medication in 2 supplies to the study site prior to study visits. intervention 2: Standard of HCV care provided by medical care provider intervention 3: Trained research staff will measure participants liver stiffness using liver ultrasonographic elastography. Research staff place ultrasound gel directly on participant's skin on the area of the torso. Research staff will position the participant's body on the exam table to assure the liver can be located, placing the small probe on the body's surface (skin with gel) and begin recording images of the participant's liver.

The procedure will take 15-30 minutes, depending on the ease with which the research staff is able to accurately locate the participant's liver.

Results from the FibroScan will be discussed with a trained provider.

Protocol documents:
Prot_SAP_000.pdf: 
ID: IN-US-342-5516 
The No One Waits Study: acceptability and feasibility of community-based point-of-diagnosis 
HCV treatment 
 
Document date: September 17, 2023 
 
 


Study design 
The NOW study is a nonrandomized, single-arm, open-label, phase 4 study evaluating the 
feasibility, acceptability, and safety of a point-of-diagnosis HCV treatment model at a non-
medical community site in San Francisco (NCT03987503).  
 
From July 2020 to October 2021, the study team screened participants for HCV infection using 
the OraQuick® HCV Rapid Antibody (Ab) test and for HIV infection using the Alere Determine™ 
HIV-1/2 Ag/Ab Combo with a fingerstick blood sample. Those who tested HIV positive without a 
prior diagnosis were referred to clinical care. For participants with a reactive HCV Ab result, on-
site venipuncture was performed for HCV RNA quantification and reflex genotype testing as well 
as hepatitis B surface antigen (HBsAg) testing. Participants returned in one week for in-person 
HCV RNA results and were offered same-day initiation of HCV treatment if their HCV RNA was 
detectable and they met eligibility criteria. Participants self-selected, rather than randomized, to 
receiving the intervention (starting HCV treatment at the HCV diagnosis visit). The study team 
provided medication through an investigator-initiated grant from Gilead Sciences and dispensed 
it to participants. Consented participants were given a 14-day starter pack of sofosbuvir 400 mg 
and velpatasvir 100 mg (SOF/VEL) and took their first dose on day of enrollment. (Figure 1).  
 
Participants  
Participants were identified through: (1) flyers and study cards posted in neighborhoods and 
venues frequented by PWID; (2) referrals from service organizations; (3) street-outreach to 
PWID and people experiencing homelessness; and (4) lists of participants in the investigators’ 
previous research studies who gave contact permission for future research.  
 
Eligibility was assessed and consent obtained at two time-points: (1) HCV screening and (2) HCV 
treatment (Figure 2). For HCV screening, eligible participants were 18 years or older and 
reported either injecting drugs in their lifetime or having a blood transfusion in or before 1992.  
Second, participants with confirmed HCV viremia were assessed for eligibility at their HCV RNA 
results disclosure. Clinical exclusion criteria included: positive HBsAg, untreated HIV, history of 
hepatic decompensation, prior treatment with an NS5A-inclusive DAA regimen for more than 2 
weeks (unless there was evidence of prior SVR12 with HCV reinfection), pregnancy or 
breastfeeding, current medication use incompatible with SOF/VEL or sofosbuvir-velpatasvir-
voxilaprevir (SOF/VEL/VOX), or a life expectancy of < 12 months as assessed by the study 
clinician.  
 
Late study exclusion criteria were considered based on pre-treatment labs (drawn at study 
entry): albumin <3.0 g/dL, hemoglobin <8.0 g/dL (women) or <9.0g/dL (men), platelets <50,000, 
creatinine clearance (estimated by Cockcroft-Gault) <30 ml/min, aspartate aminotransferase or 
alanine aminotransferase > 10 x upper limit of normal (ULN), total bilirubin >1.5 times ULN, or 
INR >1.5 times ULN. For participants with genotype 3 and suspected cirrhosis based on FIB-4 
>3.25, NS5A resistance associated substitution testing was performed using a pre-treatment 
sample to assess for the presence of the Y93H mutation; if detected, patients were switched to 
SOF/VEL/VOX. 
 


Persons not meeting eligibility criteria or who declined enrollment received harm reduction 
counseling and referrals to community-based medical clinics for HCV and medical care needs.  
 
Study enrollment and follow-up procedures. After written informed consent, participants 
completed a research questionnaire, a blood draw for pre-treatment labs (complete blood 
count [CBC], comprehensive metabolic panel [CMP] and prothrombin time; hepatitis B surface 
antibody and hepatitis B core antibody if no prior clinical documentation), received clinical 
assessment via staff-assisted telemedicine, received a 14-day SOF/VEL starter pack, and were 
observed taking the first SOF/VEL dose by the staff. The study pharmacy team submitted 
documentation to authorize participants’ transition to insurance provided SOF/VEL treatment. If 
insurance-provided medication was delayed or not authorized, participants received study-
issued SOF/VEL until insurance provided SOF/VEL was attained or for the duration of treatment.  
 
The study team scheduled follow-up visits every two weeks during the 12 weeks of treatment 
and at 4- and 12-weeks post-treatment. At each follow-up study visit, participants picked up 
medication and completed research questionnaires. For patients who missed follow-up study 
visits, medication pickup or delivery was arranged. Clinical assessments conducted via staff-
assisted telemedicine at the end of treatment. Additionally, participants were offered clinical 
consults with a clinician at treatment weeks four and eight and 12-weeks post treatment. For all 
telemedicine visits, staff set up the telemedicine technology on a computer provided by the 
study and introduced the clinician. The telemedicine visit was led by a physician or clinical nurse 
practitioner. 
 
Enrollment and follow-up questionnaires collected demographics, physical and emotional 
health, current living context, healthcare access, sexual and drug use behaviors, and medication 
adherence. Study blood draws were obtained at treatment mid-point and completion and at 
≥least 12-weeks post-treatment. We approach research participation as a form of specialized 
work and consulted our community advisory board to determine suitable compensation1,2. 
Participants received reimbursement ranging from $20 to $60 per visit, with a total potential 
compensation of up to $325 USD over the course of the 10 study visits.  
Research site 
The study was conducted at: (1) a fixed community space located in a neighborhood close to 
public transit and social service organizations, in an area where PWID were known to 
congregate; and (2) a mobile medical van parked in the neighborhood with the highest 
percentage of African American and Black people in San Francisco and few city-supported social 
or medical service organizations. In 2018 and 2019, Black/African-American San Franciscans 
made up approximately a quarter of HCV cases reported despite being only about 5% of the 
overall population.3 Study procedures at the mobile site were discontinued in January 2021 due 
to COVID-19 and participants were rolled over to the fixed site. Both sites had private spaces for 
interviews and clinical research activities. Wrap-around services, including food, harm reduction 
supplies, COVID information and vaccination, were also available. Site staff were trained in HIV 
and HCV testing and disclosure counseling, harm reduction, ethical human research practices 
and de-escalation methods.  
 


Study materials were refined in partnership with local advocacy organizations and members of 
the target population. The study protocol was approved by the University of California, San 
Francisco Institutional Review Board (protocol number 19-27751). 
 
Endpoint measures 
Acceptability, feasibility, and safety of HCV treatment were assessed for all participants who 
received the intervention, starting HCV treatment (defined as receiving at least one dose of 
study drug) at the HCV status disclosure visit. The primary treatment feasibility outcome 
measure was treatment response defined as undetectable HCV RNA at least 12 weeks post-
treatment (SVR12). SVR12 was calculated by intention-to-treat (ITT group), defined as those 
who initiated treatment, and per-protocol (PP group) defined as those who completed a 12-
week course of DAA therapy. Participants with undetected HCV RNA after treatment completion 
who subsequently developed HCV viremia with an HCV genotype different from their pre-
treatment genotype within 12 weeks of DAA completion were considered to have post-
treatment reinfection within 12 weeks and were classified as not achieving SVR12. Secondary 
treatment feasibility endpoints were undetectable HCV RNA at treatment completion. Primary 
acceptability endpoints included treatment initiation at time of HCV RNA result disclosure and 
treatment completion. Safety endpoints were treatment discontinuation because of late 
exclusion criterion or adverse event.  
 
Statistical analyses 
All acceptability and safety results and secondary outcomes were summarized with descriptive 
statistics. Treatment initiation was evaluated among all participants with current HCV infection 
meeting eligibility who returned for their HCV RNA results disclosure visit. Treatment response 
was evaluated among those who initiated treatment (ITT group, N=87) and those who 
completed DAA therapy (PP group, N=69. Point estimates and two-sided 95% confidence 
intervals were also calculated for primary endpoints. Significance assessments were conducted 
using appropriate statistical tests, with p-values calculated using either the Wilcoxon rank-sum 
test for continuous or ordinal data, or chi-squared tests and Fisher's exact test for categorical 
data, based on the nature of the variables and data distribution. All analyses were performed 
using STATA software version 15.4 
 
References  
1. 
Davidson P, Page K. Research participation as work: comparing the perspectives of 
researchers and economically marginalized populations. Am J Public Health. Jul 
2012;102(7):1254-9. doi:10.2105/ajph.2011.300418 
2. 
Abadie R, Brown B, Fisher CB. "Money Helps": People who inject drugs and their 
perceptions of financial compensation and its ethical implications. Ethics & behavior. 
2019;29(8):607-620. doi:10.1080/10508422.2018.1535976 
3. 
San Francisco Department of Public Health (SFDPH). Hepatitis C Infection Surveillance 
Report 2018-2019. 2021. Accessed December 2022. https://endhepcsf.org/wp-
content/uploads/2021/07/SFDPH-Hepatitis-C-Infection-Surveillance-Report-2018-2019.pdf 
4. 
Stata Statistical Software: Release 15. StataCorp LLC; 2017.