Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World

Study Overview
=================
Brief Summary
-----------------
The main purpose of the study is to evaluate the efficacy, safety and tolerability of a medication, ledipasvir/sofosbuvir (LDV/SOF), used to treat individuals with chronic hepatitis C virus (HCV) in Rwandan adults. A sub-cohort of participants will have limited laboratory monitoring to determine the minimum laboratory tests necessary.

Detailed Description
-----------------
This is an open-label single arm study that will evaluate the antiviral efficacy, safety and tolerability of ledipasvir/sofosbuvir fixed dose combination administered for 12 weeks in HCV treatment-naive and treatment-experienced participants with chronic genotype 1 or 4 HCV infection. Approximately 240 participants will be enrolled and treated with sofosbuvir (SOF) 400 mg/LDV 90 mg fixed dose combination (FDC) one tablet once daily for 12 weeks in the SHARED 1 study. Sixty additional participants will be enrolled in the SHARED 2 sub-cohort with laboratory monitoring blinded to study clinicians.

Official Title
-----------------
Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World

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

Intervention / Treatment
-----------------
* Drug: sofosbuvir/ledipasvir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients that are willing and able to provide written informed consent age ≥ 18 years HCV RNA ≥ 103 IU/mL HCV genotype 1 or 4 screening ultrasound excluding hepatocellular carcinoma (HCC) acceptable laboratory values (hemoglobin ≥8.0 g/dL, platelet count ≥40,000/mm3; AST, ALT, and alkaline phosphatase ≤10 × ULN; creatinine clearance ≥30 mL/min) general good health ability to comply with study procedures HIV-infected patients must have completed at least 6 months of any approved HIV antiretroviral therapy (ART) per Rwanda National Guidelines 2013, have been taking for at least 2 weeks prior to screening ART compatible with SOF/LDV (efavirenz, rilpivirine, raltegravir, dolutegravir, emtricitabine, lamivudine, zidovudine, tenofovir), have screening HIV RNA < 200 copies/mL, and have screening CD4 T-cell count of ≥100 cells/µL 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 active Hepatitis B infection difficulty with blood collection and/or poor venous access for the purposes of phlebotomy any IFN-containing regimen within 8 weeks prior to screening or any prior exposure to HCV-specific direct-acting antiviral agent (other than a NS3/4A protease inhibitor and SOF), current pregnancy or breastfeeding, and active drug or alcohol use or dependence

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Harvoni<br>sofosbuvir/ledipasvir once daily for 12 weeks | Drug: sofosbuvir/ledipasvir<br> <br> * Other names: Harvoni;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with sustained viral response as defined by an HCV RNA below the limit of quantification 12 weeks after discontinuation of study treatment | To determine the hepatitis C virus (HCV) antiviral efficacy of sofosbuvir/ledipasvir (SOF/LDV) fixed-dose combination (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 (24 weeks) | 
| Proportion of participants with sustained viral response as defined by an HCV RNA below the limit of quantification 12 weeks after discontinuation of study treatment, with limited lab monitoring | To determine the HCV antiviral efficacy of SOF/LDV FDC, as measured by the proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12), with limited lab monitoring in Rwanda. | After study completion (24 weeks) | 
| Proportion of participants with a new grade 3 or 4 adverse event or premature study drug discontinuation due to an adverse event. | To evaluate the safety and tolerability of SOF/LDV FDC in Rwanda | After study completion (24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A set of minimum required monitoring tests | A set of minimum required monitoring tests | After study completion (24 weeks) | 
| Distribution of HCV genotypes subtypes among participants | Distribution of HCV genotypes subtypes among participants | After study completion (24 weeks) | 
| SVR12, stratified by genotypic subtype | SVR12, stratified by genotypic subtype | After study completion (24 weeks) | 
| Basic demographic and clinical characteristics of patients referred for HCV treatment | Basic demographic and clinical characteristics of patients referred for HCV treatment | After study completion (24 weeks) | 
| Adherence to SOF/LDV measured by pill count | Adherence to SOF/LDV measured by pill count | After 12 weeks medication therapy | 
| Proportion of participants with virologic failure | Proportion of participants with virologic failure | After study completion (24 weeks) | 
| Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatment | Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatment | After study completion (24 weeks) | 
| Proportion of HIV co-infected participants that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment | Proportion of HIV co-infected participants that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment | After 12 weeks of medication therapy | 
| Proportion of participants reporting increased quality of life after SVR12 using the Medical Outcomes Study HIV Health Survey | To determine the effect of SOF/LDV and SVR12 on quality of life in Rwanda | After study completion (24 weeks) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis C Virus, sofosbuvir/ledipasvir, Efficacy