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

Phase 4
Completed
Conditions
Chronic Hepatitis C
Interventions
Registration Number
NCT02964091
Lead Sponsor
Partners in Health
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
300
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Harvonisofosbuvir/ledipasvirsofosbuvir/ledipasvir once daily for 12 weeks
Primary Outcome Measures
NameTimeMethod
Proportion of participants with sustained viral response as defined by an HCV RNA below the limit of quantification 12 weeks after discontinuation of study treatmentAfter study completion (24 weeks)

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.

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 monitoringAfter study completion (24 weeks)

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.

Proportion of participants with a new grade 3 or 4 adverse event or premature study drug discontinuation due to an adverse event.After study completion (24 weeks)

To evaluate the safety and tolerability of SOF/LDV FDC in Rwanda

Secondary Outcome Measures
NameTimeMethod
SVR12, stratified by genotypic subtypeAfter study completion (24 weeks)

SVR12, stratified by genotypic subtype

A set of minimum required monitoring testsAfter study completion (24 weeks)

A set of minimum required monitoring tests

Distribution of HCV genotypes subtypes among participantsAfter study completion (24 weeks)

Distribution of HCV genotypes subtypes among participants

Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatmentAfter study completion (24 weeks)

Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatment

Basic demographic and clinical characteristics of patients referred for HCV treatmentAfter study completion (24 weeks)

Basic demographic and clinical characteristics of patients referred for HCV treatment

Adherence to SOF/LDV measured by pill countAfter 12 weeks medication therapy

Adherence to SOF/LDV measured by pill count

Proportion of participants with virologic failureAfter study completion (24 weeks)

Proportion of participants with virologic failure

Proportion of HIV co-infected participants that maintain HIV-1 RNA< 200 copies/mL while on HCV treatmentAfter 12 weeks of medication therapy

Proportion of HIV co-infected participants that maintain HIV-1 RNA\< 200 copies/mL while on HCV treatment

Proportion of participants reporting increased quality of life after SVR12 using the Medical Outcomes Study HIV Health SurveyAfter study completion (24 weeks)

To determine the effect of SOF/LDV and SVR12 on quality of life in Rwanda

Trial Locations

Locations (1)

Rwanda Military Hospital

🇷🇼

Kanombe, Kigali, Rwanda

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