GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection
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ClinicalTrials.gov Identifier: NCT01435226 |
Recruitment Status
:
Completed
First Posted
: September 16, 2011
Last Update Posted
: December 17, 2013
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hepatitis C, Chronic | Drug: GS-5885 Drug: GS-9451 Drug: tegobuvir Drug: placebo to match tegobuvir Drug: placebo to match RBV Drug: Ribavirin | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 170 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared With GS-5885, GS-9451 With Tegobuvir or RBV in Treatment-Experienced Subjects With Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection |
Study Start Date : | September 2011 |
Actual Primary Completion Date : | January 2013 |
Actual Study Completion Date : | July 2013 |
Arm | Intervention/treatment |
---|---|
Active Comparator: Arm 1
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID
|
Drug: GS-5885
Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD tegobuvir 30 mg BID
Drug: Ribavirin
Ribavirin (Copegus®) BID (1000 mg for subjects weighing < 75 kg and 1200 mg for subjects weighing ≥ 75 kg) divided BID
|
Active Comparator: Arm 2
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID
|
Drug: GS-5885
Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD tegobuvir 30 mg BID
Drug: placebo to match RBV
Ribovirin placebo BID
|
Active Comparator: Arm 3
GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID
|
Drug: GS-5885
Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD tegobuvir placebo BID
Drug: Ribavirin
Ribavirin (Copegus®) BID (1000 mg for subjects weighing < 75 kg and 1200 mg for subjects weighing ≥ 75 kg) divided BID
|
- Safety and Tolerability [ Time Frame: 24 weeks ]
To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin.
Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.
- Antiviral Activity [ Time Frame: 24 weeks ]To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA < lower limit of quantitation [LLoQ] 24 weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and RBV compared with GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and RBV in treatment-experienced subjects with chronic genotype 1a or 1b HCV infection
- Viral Dynamics [ Time Frame: 10 days ]To characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 10 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir.
- Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics [ Time Frame: predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose ]To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau and T ½
- Antiviral Efficacy [ Time Frame: 24-48 weeks ]To evaluate the antiviral efficacy (as defined by SVR) of adding pegylated interferon alfa-2a (PEG) and RBV (Arm 2 only) for 24-48 weeks to the original treatment regimen in subjects who experience viral breakthrough or relapse and enter the Rescue Therapy Substudy

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age ≥18 years with chronic HCV infection
- Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
- Monoinfection with HCV genotype (GT) 1a or 1b
- HCV RNA ≥ 104 IU/mL at screening
- Prior treatment and adherence with one course of pegylated interferon alfa and RBV
- The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
- Body mass index (BMI) 18-40 kg/m2 inclusive
-
Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)
≤ 450 msec for males and ≤ 470 msec for females.
- Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.
Exclusion Criteria:
- Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
- History of significant cardiac disease
- Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
- Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
- Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01435226

Study Director: | John McNally, PhD | Gilead Sciences |
Responsible Party: | Gilead Sciences |
ClinicalTrials.gov Identifier: | NCT01435226 History of Changes |
Other Study ID Numbers: |
GS-US-248-0131 |
First Posted: | September 16, 2011 Key Record Dates |
Last Update Posted: | December 17, 2013 |
Last Verified: | November 2013 |
Keywords provided by Gilead Sciences:
Hepatitis C HCV Rapid Virologic Response Sustained Virologic Response Direct Acting Antiviral Combination Therapy Tegobuvir Treatment Experienced HCV RNA |
Polymerase inhibitor Protease inhibitor Interferon intolerant Interferon ineligible GS-9190 GS-9451 GS-5885 Chronic Genotype 1a or 1b |
Additional relevant MeSH terms:
Hepatitis Hepatitis A Hepatitis C Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections |
Flaviviridae Infections Hepatitis, Chronic Interferons Ribavirin Ledipasvir Antineoplastic Agents Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action |