A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Comparing 24 or 48 Weeks of GS 9190, in Combination With Peginterferon Alfa 2a and Ribavirin, to 48 Weeks of Peginterferon Alfa 2a and Ribavirin for the Treatment of Genotype-1 Chronic Hepatitis C Virus (HCV) Infection (GS-US-196-0103)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 252
- 主要终点
- Undetectable HCV RNA level
研究概览
简要总结
The purpose of this study is to compare the safety, tolerability and effectiveness of the experimental drug GS-9190 when administered for 24 or 48 weeks with peginterferon alfa 2a and ribavirin for the treatment of genotype-1 chronic hepatitis C infection.
详细描述
The safety, tolerability and antiviral efficacy GS-9190, administered orally twice daily at 40 mg, will be compared to placebo when used in combination with peginterferon alfa 2a (PEG) and ribavirin (RIBA) in treatment-naïve subjects chronically infected with HCV genotype 1 infection. Two-hundred forty-eight (248) subjects will be randomized (ratio: 1:2:1) to one of three treatment arms:
Arm 1: PEG/RIBA + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 62)
Arm 2: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 124)
Arm 3: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 62).
Randomization will be stratified by plasma HCV RNA level (< or ≥ 400,000 IU/mL) at screening and race (of African descent or other).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects (18 - 70 years of age)
- •Chronic HCV infection for at least 6 months prior to Baseline (Day 1) (anti-HCV antibody positive; positive for plasma HCV RNA; medical history consistent with chronicity accepted by the investigator)
- •Liver biopsy results within the past 2 years prior to Baseline (Day 1) indicating the absence of cirrhosis
- •HCV treatment-naive, defined as no prior exposure to PEG, RIBA, or experimental HCV therapy
- •Mono-infection with HCV genotype 1a or 1b
- •Detectable plasma HCV RNA at Screening
- •BMI between 19 and 36 kg/m2
- •Willing and able to provide written informed consent and to comply with all study requirements
- •Of generally good health as determined by the Investigator
- •Subject agrees to use adequate skin protection (e.g., sunblocking agent) when exposed to the sun.
- •Women of childbearing potential (i.e., a non-menopausal female or a female with menopausal < 2 years, who has not had a hysterectomy, bilateral oophorectomy or medically documented ovarian failure) must have negative serum β-human chorionic gonadotropin (hCG) at screening and negative urine pregnancy test prior to the first study drug administration.
- •All subjects (male and female) must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study treatment and for 24 weeks after the last dose of RIBA.
- •Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
- •Female subjects who are postmenopausal for less than two years are required to have FSH > 40 mIU/mL. If the FSH is ≤ 40 mIU/mL, the subject must agree to use highly effective method of birth control (as described above) to participate in the study.
- •Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening through completion of the study and continue for 24 weeks after the last dose of RIBA
排除标准
- •Pregnant or breast feeding women or women who may wish to become pregnant during the course of the study
- •Males who have partners planning to become pregnant
- •Males and females of reproductive potential who are unwilling to use two forms of effective birth control through Study Week
- •One method should include a condom with spermicide for males
- •Infection with non-genotype 1 HCV
- •Poorly controlled diabetes mellitus (hemoglobin A1c > 7) unless treatment intervention has been reviewed with the Medical Monitor and improved glucose control is anticipated
- •History of sarcoidosis
- •History of hemoglobinopathy (e.g., thalassemia)
- •History of known retinal disease
- •History of invasive malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screen)
- •Evidence of hepatocellular carcinoma
- •Chronic liver disease of a non-HCV etiology
- •Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, or a history of a suicide attempt
- •Co-infection with HIV, HBV, or multiple HCV genotypes
- •Chronic use of systemic immunosuppressive agents
- •Presence of autoimmune disorders. Subjects with treated hypothyroidism with normal TSH may be enrolled.
- •Severe chronic obstructive pulmonary disease
- •History of clinically significant cardiac disease, including a family history of Long QT Syndrome, and/or evidence of the following ECG abnormalities at screening: QTcF (QT corrected using Fridericia's formula) of > 450 msec; complete or incomplete left or right bundle branch block; intraventricular conduction delay with QRS duration of > 120 msec; bradycardia (< 45 beats per minute); pathologic Q-waves (Q wave of > 40 msec or depth of > 0.4 to 0.5 V); arrhythmia (an isolated premature ventricular contraction on screening/Day 1 is not exclusionary) ; ventricular pre excitation; second or third degree heart block
- •Positive urine screen for amphetamines or cocaine
- •Known, current heroin, morphine, or methadone use
- •Ongoing alcohol abuse in the judgment of the investigator (in no case intake of more than 28 units of alcohol per week [1 unit = ½ pint of beer, 1 glass of wine, 1 shot of spirits])
- •Receiving a known potent CYP 3A4 inhibitor within 2 weeks of study drug dosing or are expected to receive such therapy during the course of study drug dosing
- •Known hypersensitivity to the study drugs, their metabolites or formulation excipients
- •In the judgment of the Investigator, should not participate in the study due to potential clinical or compliance issues
研究组 & 干预措施
1
Peginterferon and ribavirin + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 50)
干预措施: placebo (Drug)
1
Peginterferon and ribavirin + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 50)
干预措施: Peginterferon Alfa 2a (Drug)
1
Peginterferon and ribavirin + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 50)
干预措施: Ribavirin (Drug)
2
Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 100)
干预措施: GS-9190 (Drug)
2
Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 100)
干预措施: Peginterferon Alfa 2a (Drug)
2
Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 100)
干预措施: Ribavirin (Drug)
3
Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 50).
干预措施: GS-9190 (Drug)
3
Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 50).
干预措施: Peginterferon Alfa 2a (Drug)
3
Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 50).
干预措施: Ribavirin (Drug)
结局指标
主要结局
Undetectable HCV RNA level
时间窗: At Week 12 for Early Virologic Response (EVR)
次要结局
- Safety and tolerability(Throughout 72 week study period)
- Undetectable HCV RNA(At Week 72 for sustained virologic response (SVR))
- Undetectable HCV RNA level(Week 4, Week 24 and Week 48)
- GS-9190 plasma concentrations(Through Week 48)