A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic HCV GT3 Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 101
- 主要终点
- Percentage of Participants Experiencing an Adverse Event (AE)
研究概览
简要总结
This is a randomized, multi-site, open-label trial of the co-administration of a fixed-dose combination (FDC) of EBR 50 mg + GZR (100 mg) (EBR/GZR) and SOF 400 mg, with and without RBV, in treatment-naïve (TN) and treatment-experienced (TE) participants with chronic HCV GT3 infection with compensated cirrhosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •has HCV RNA (>= 10,000 IU/mL in peripheral blood) at screening
- •has documented HCV GT3 (with no evidence of non-typeable or mixed GT infection)
- •has compensated cirrhosis of the liver
- •has liver imaging within 6 months of Day 1 with no evidence of hepatocellular carcinoma (HCC)
- •is either HCV TN or TE (i.e., has documented prior virologic failure or intolerance to peg-interferon/ribavirin)
- •is otherwise healthy as determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements
- •has compensated cirrhosis of the liver
- •is TN or TE (i.e., documented prior virologic failure or intolerance to peg-interferon/ribavirin)
- •is not of reproductive potential, or agrees to not impregnate a partner or become pregnant for at least 2 weeks prior to the first dose of study drug, and for 7 months after the final dose of study drug (or longer if dictated by local regulations)
排除标准
- •has previously received one or more doses of a direct-acting antiviral (DAA)
- •has evidence of decompensated liver disease
- •is coinfected with hepatitis B (hepatitis B surface antigen [HBsAg] positive)
- •has a recent (within 5 years) history of malignancy or is under evaluation for HCC or other suspected malignancy
- •is currently or has participated (within past 30 days) in a study with an investigational compound
- •has clinically-relevant drug or alcohol abuse within the past 12 months of screening
- •is a female and is pregnant or breast-feeding
- •is a male whose female partner is/are pregnant
- •has any of the following:
- •organ transplants
- •poor venous access
- •history of gastric surgery or malabsorption disorder
- •current or history of clinically significant cardiac abnormalities or dysfunction
- •chronic pulmonary disease
- •hemoglobinopathy
- •history of hospitalization within 3 months prior to enrollment
- •medical or surgical condition that may result in need for hospitalization during the course of the study
- •any condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppresant drugs during the course of the study
- •any condition, prestudy laboratory or ECG abnormality, or history of any illness, which could confound results of the study or pose additional risks in administering study drugs in the opinion of the investigator
- •has a life-threatening serious AE (SAE) during the screening period
- •has evidence of history of chronic hepatitis not caused by HCV
研究组 & 干预措施
Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks
TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks.
干预措施: Grazoprevir (Drug)
Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks
TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks.
干预措施: Elbasvir (Drug)
Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks
TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks.
干预措施: Ribavirin (Drug)
Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks
TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks.
干预措施: Sofosbuvir (Drug)
Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks
TN HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.
干预措施: Grazoprevir (Drug)
Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks
TN HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.
干预措施: Elbasvir (Drug)
Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks
TN HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.
干预措施: Sofosbuvir (Drug)
Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.
干预措施: Grazoprevir (Drug)
Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.
干预措施: Elbasvir (Drug)
Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks.
干预措施: Sofosbuvir (Drug)
Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks.
干预措施: Grazoprevir (Drug)
Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks.
干预措施: Elbasvir (Drug)
Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks.
干预措施: Ribavirin (Drug)
Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks.
干预措施: Sofosbuvir (Drug)
Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
干预措施: Grazoprevir (Drug)
Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
干预措施: Elbasvir (Drug)
Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks
TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks.
干预措施: Sofosbuvir (Drug)
结局指标
主要结局
Percentage of Participants Experiencing an Adverse Event (AE)
时间窗: Up to 18 weeks (up to 2 weeks after completion of study treatment)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants Achieving SVR12 (Sustained Virologic Response 12 Weeks After the End of All Study Therapy)
时间窗: Up to Week 28
The percentage of participants achieving SVR12 (i.e., HCV ribnonucleic acid \[RNA\] \< Lower Limit of Quantification \[LLOQ\] 12 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.
Percentage of Participants Discontinuing From Study Therapy Due to an AE
时间窗: Up to 16 weeks
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
次要结局
- Percentage of Participants Achieving SVR24 (Sustained Virologic Response 24 Weeks After the End of All Study Therapy)(Up to Week 40)