Simplifying HCV Treatment in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)

Study Overview
=================
Brief Summary
-----------------
The main purpose of the study is to determine the antiviral efficacy and evaluate the safety and tolerability of sofosbuvir/ velpatasvir (SOF/VEL) and sofosbuvir/ velpatasvir/ voxilaprevir (SOF/VEL/VOX) used to treat individuals with chronic hepatitis C virus infection in Rwanda adults.

Detailed Description
-----------------
This is an open-label single-arm study that will examine the antiviral efficacy, safety and tolerability of 12 weeks daily therapy with fixed dose combination (FDC) of SOF/VEL and SOF/VEL/VOX administered respectively in HCV-infected treatment-naïve adult participants and in HCV-infected individuals with a history of virologic failure to SOF/LDV or other DAA-containing regimen. A total of 100 participants will be enrolled in this portion of the SHARED study, labelled the SHARED 3 study: 60 treatment-naïve participants and 40 individuals with history of virologic failure to SOF/LDV or other DAA-containing regimen

Official Title
-----------------
Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)

Conditions
-----------------
Hepatitis C, Chronic

Intervention / Treatment
-----------------
* Drug: sofosbubir/velpatasvir
* Drug: sofosbubir/velpatasvir/voxilaprevir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing and able to provide written informed consent Age ≥ 18 years HCV RNA >1000 IU/mL at Screening For SOF/VEL arm, HCV treatment-naïve or interferon/ribavirin-experienced For SOF/VEL/VOX arm, history of virologic failure to SOF/LDV or other DAA-containing regimen as defined by a quantifiable HCV viral load any time at or after the end of HCV therapy Screening ultrasound excluding hepatocellular carcinoma (HCC) Acceptable laboratory values including: Hemoglobin ≥8.0 g/dL Platelet count ≥40,000/mm3 AST, ALT, and alkaline phosphatase ≤10 × ULN Calculated creatinine clearance (CrCl) ≥30 mL/min General good health Ability to comply with the dosing instructions for study drug administration and to complete the study schedule of assessments If HIV-infected: The participant must have completed at least 6 months of any approved HIV antiretroviral therapy (ART) before starting enrollment The participant at time of screening and for at least 2 weeks prior to screening must be on ART compatible with SOF/VEL and SOF/VEL/VOX Screening HIV RNA < 200 copies/mL Screening CD4 T-cell count of ≥100 cells/µL Women of reproductive potential must have a negative urine pregnancy test at Screening and a negative urine pregnancy test at Entry prior to enrollment. Exclusion Criteria: Current or history of clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage) Active tuberculosis Other clinically-significant illness (except HCV and/or HIV) or any other major medical disorder that, in the opinion of the site investigator, may interfere with participant treatment, assessment or compliance with the protocol; participants currently under evaluation for a potentially clinically-significant illness (other than HCV/HIV) are also excluded. Active Hepatitis B infection Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy Pregnant or nursing female Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study procedures and treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be assigned to one of the following two groups in parallel for the duration of the study, based on treatment indication to be put on SOF/VEL or SOF/VEL/VOX: sofosbubir/velpatasvir (SOF/VEL) FDC once daily for 12 weeks will be administered to HCV-infected individuals naïve to DAA therapy regimen (in this group we consider also HCV-infected individuals who have failed interferon-based therapy) who meet other eligibility criteria; sofosbubir/velpatasvir /voxilaprevir (SOF/VEL/VOX) FDC once daily for 12 weeks will be administered to HCV treatment-experienced participants (i.e. HCV-infected individuals with a history of virologic failure to SOF/LDV or other DAA-containing regimen) who meet other eligibility criteria.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HCV treatment-naïve participants<br>HCV-infected individuals naïve to DAA therapy regimen; in this group we consider also HCV-infected individuals who have failed interferon-based therapy. Sofosbubir/velpatasvir (SOF/VEL) will be administered once daily for 12 weeks to eligible HCV treatment-naïve participants. | Drug: sofosbubir/velpatasvir<br>* SOF/VEL (400 mg/100 mg) FDC once daily<br>* Other names: Epclusa;|
| Experimental: HCV treatment-experienced participants<br>HCV treatment-experienced participants, i.e.HCV-infected individuals with a history of virologic failure to SOF/LDV or other DAA-containing regimen. Sofosbubir/velpatasvir /voxilaprevir (SOF/VEL/VOX) will be administered once daily for 12 weeks to eligible HCV treatment-experienced participants | Drug: sofosbubir/velpatasvir/voxilaprevir<br>* SOF/VEL/VOX (400 mg/100 mg/100 mg) FDC once daily<br>* Other names: Vosevi;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12) | Antiviral efficacy of SOF/VEL FDC and SOF/VEL/VOX FDC as measured by the proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12) in Rwanda | After study completion (week 24) | 
| Proportion of patients treated with SOF/VEL FDC and SOF/VEL/VOX FDC with a new grade 3 or 4 adverse event as defined by the DAIDS Scales or with premature study drug discontinuation due to an adverse event | Proportion of patients treated with SOF/VEL FDC and SOF/VEL/VOX FDC with a new grade 3 or 4 adverse event as defined by the DAIDS Scales or with premature study drug discontinuation due to an adverse event | After study completion (week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants by HCV genotype subtypes with SVR12 after completing treatment with SOF/VEL FDC and SOF/VEL/VOX FDC | Proportion of participants by HCV genotype 4 subtype with SVR12 after completing the study treatment with SOF/VEL FDC and SOF/VEL/VOX FDC | After study completion (week 24) | 
| Adherence to SOF/VEL FDC and SOF/VEL/VOX FDC | Proportion of participants with adequate adherence to SOF/VEL FDC and SOF/VEL/VOX FDC measured by pill count >90% of pills taken | After study completion (week 24) | 
| Odds ratio for achievement of SVR12 by treatment type for the following variables: age (per 10 year increase), female sex, HIV co-infection, genotype subtype 4r, baseline HCV viral load (per 1 log increase), APRI > 1.0 | Odds ratio for achievement of SVR12 by treatment type for the following variables: age (per 10 year increase), female sex, HIV co-infection, genotype subtype 4r, baseline HCV viral load (per 1 log increase), APRI > 1.0 | After study completion (week 24) | 
| Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment | Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment, with HIV-1 RNA test performed at completion of the study treatment (week 12) | After study completion (week 24) | 
| Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life | Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life, using the MOS HIV questionnaire, with proportion of patients showing significant improvement on physical quality of life and mental quality of life from pre- to post- treatment | After study completion (week 24) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis C, direct-acting antiviral, Rwanda