Chronic Hepatitis C
Conditions
Keywords
Hepatitis C Virus, sofosbuvir/ledipasvir, Efficacy
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.
Interventions
Sponsors
Partners in Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | After 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 monitoring | After 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
| Measure | Time frame | Description |
|---|---|---|
| Basic demographic and clinical characteristics of patients referred for HCV treatment | After study completion (24 weeks) | Basic demographic and clinical characteristics of patients referred for HCV treatment |
| Adherence to SOF/LDV measured by pill count | After 12 weeks medication therapy | Adherence to SOF/LDV measured by pill count |
| Proportion of participants with virologic failure | After study completion (24 weeks) | Proportion of participants with virologic failure |
| A set of minimum required monitoring tests | After study completion (24 weeks) | A set of minimum required monitoring tests |
| 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 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 Survey | After study completion (24 weeks) | To determine the effect of SOF/LDV and SVR12 on quality of life in Rwanda |
| Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatment | After study completion (24 weeks) | Proportion of participants with HCV RNA below the level of quantitation (BLQ) while on treatment |
| Distribution of HCV genotypes subtypes among participants | After study completion (24 weeks) | Distribution of HCV genotypes subtypes among participants |
| SVR12, stratified by genotypic subtype | After study completion (24 weeks) | SVR12, stratified by genotypic subtype |
Countries
Rwanda
Outcome results
None listed