The No One Waits Study: Acceptability and Feasibility of Community-based Point-of-diagnosis HCV Treatment Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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The No One Waits Study: Acceptability and Feasibility of Community-based Point-of-diagnosis HCV Treatment Study

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Epclusa (SOF/VEL)
* Drug: Standard of care
* Device: Fibroscan® 430 Mini Plus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age anti-HCV and HCV RNA positive, interested in starting HCV treatment at the time of diagnosis Women of childbearing potential engaged in sexual activity that could lead to pregnancy must consent to use contraception and agree to pregnancy testing during treatment If currently not enrolled in insurance, agree to assistance to enroll in insurance Exclusion Criteria: HBsAg positive from pre-screening visit and no medically controlled hepatitis B virus (HBV) condition History of hepatic decompensation (ascites, hepatic encephalopathy, or variceal hemorrhage). Current use of medications that is not compatible with SOF/VEL use, according to current prescribing guidelines, including amiodarone or a proton pump inhibitor exceeding 20 mg of omeprazole equivalent. Prior treatment with an NS5a based HCV treatment regimen with subsequent viral rebound. Participants who have clear HCV reinfection as defined by an HCV GT that is different from the original genotype may enroll. If genotype results are not available from the initial and subsequent HCV infection, the individual will not be enrolled unless participant can provide SVR-12 record confirming HCV cure. Pregnancy or breastfeeding. Life expectancy of < 12 months as assessed by study clinical health provider. Late exclusion criteria: Participants with the following lab values at week 0 will be evaluated on a case by case basis for continuation of SOF/VEL at the week 2 visit Albumin < 3.0 Hemoglobin < 8.0 (women) and < 9.0 g/dl ( men) Platelet count < 50,000 creatinine (Cr) clearance (estimated by Cockcroft-Gault) < 30 ml/min aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) > 10 x ULN Total bilirubin > 1.5x ULN (for participants on atazanavir, > 3 x ULN), international normalized ratio (INR) > 1. 5 x ULN

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: at Point-of-Diagnosis HCV treatment<br>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. | Drug: Epclusa (SOF/VEL)<br>* 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.<br>Device: Fibroscan® 430 Mini Plus<br>* 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.<br>* Other names: Fibroscan;|
| Active Comparator: Passive observation<br>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). | Drug: Standard of care<br>* Standard of HCV care provided by medical care provider<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR-12 | The number and proportion attaining SVR12 after POD HCV treatment, overall,using a modified intention to treat analysis (participants taking one or more doses of SOF/VEL). | 24 weeks from the start of treatment | 
| SVR-12, by project site | The number and proportion attaining SVR12 after POD HCV treatment, by site, using a modified intention to treat analysis (participants taking one or more doses of SOF/VEL). | 24 weeks from the start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from HCV testing to treatment initiation | Time from HCV testing visit to treatment initiation | 24 weeks | 
| Time from HCV testing to treatment completion | Time from HCV testing visit to treatment completion | 24 weeks | 
| Time from HCV testing to SVR-12. | Time from HCV testing visit to SVR-12 | 24 weeks | 
| Treatment adherence | Adherence as estimated by pill count at 4-week intervals, week 4 HCV viral load, and self-disclosure treatment adherence. | 12 weeks | 
| Treatment adherence at 4 weeks | Adherence as estimated by pill count estimated as the average using self-report pill count taken divided by 28 pills. | 4 weeks from treatment initiation | 
| Treatment adherence at 8 weeks | Adherence as estimated by pill count estimated as the average using self-report pill count taken divided by 56 pills. | 8 weeks from treatment initiation | 
| Treatment adherence at 12 weeks | Adherence as estimated by pill count estimated as the average using self-report pill count taken divided by 84 pills. | 12 weeks from treatment initiation | 
| Treatment adherence | Adherence as estimated by HCV viral load test (PCR) at 4 weeks | 4 weeks from treatment initiation | 
| Treatment adherence | Adherence as estimated by HCV viral load test (PCR) at 12 weeks | 12 weeks from treatment initiation | 
| Acceptability: Number of persons who decline POD treatment | Number of persons who decline POD treatment | 1 day | 
| Acceptability: median age by declined | Comparison of median age by declined POD treatment group vs POD treatment initiate group. | 1 day | 
| Acceptability: percent female by declined | Comparison of percent female by declined POD treatment group vs POD treatment initiate group. | 1 day | 
| Acceptability: percent non-white race/ethnicity by | Comparison of percent non-white race/ethnicity by declined POD treatment group vs POD treatment initiate group. | 1 day | 
| Acceptability: percent homeless in past 30 days | Comparison of percent homeless in past 30 days by declined POD treatment group vs POD treatment initiate group. | 1 day | 
| Acceptability: percent injected drugs in past 30 days | Comparison of percent injected drugs in past 30 days by declined POD treatment group vs POD treatment initiate group. | 1 day | 
| Acceptability: percent jail/prison stay in past 30 days | Comparison of percent jail/prison stay in past 30 days by declined POD treatment group vs POD treatment initiate group. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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People who inject drugs, Homeless, Community-based testing and treatment