Simplifying Hepatitis C Antiviral Therapy in Rwanda for Elsewhere in the Developing World: Pangenotypic and Retreatment Study (SHARED3)
试验速览
- 阶段
- 4 期
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
HCV treatment-naïve participants
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.
干预措施: sofosbubir/velpatasvir (Drug)
HCV treatment-experienced participants
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
干预措施: sofosbubir/velpatasvir/voxilaprevir (Drug)
结局指标
主要结局
Proportion of participants with sustained viral response 12 weeks after discontinuation of study treatment (SVR12)
时间窗: After study completion (week 24)
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
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
时间窗: 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
次要结局
- Proportion of participants by HCV genotype subtypes with SVR12 after completing treatment with SOF/VEL FDC and SOF/VEL/VOX FDC(After study completion (week 24))
- Proportion of HIV co-infected subjects that maintain HIV-1 RNA< 200 copies/mL while on HCV treatment(After study completion (week 24))
- Adherence to SOF/VEL FDC and SOF/VEL/VOX FDC(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(After study completion (week 24))
- Effect of SOF/VEL FDC and SOF/VEL/VOX FDC and SVR12 on quality of life(After study completion (week 24))