GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection - Full Text View

Purpose

This is 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.

Condition	Intervention	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
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Safety and Tolerability [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
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

Secondary Outcome Measures:

Viral Dynamics [ Time Frame: 10 days ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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


Enrollment:	170
Study Start Date:	September 2011
Study Completion Date:	July 2013
Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD Drug: tegobuvir 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 Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD Drug: tegobuvir 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 Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD Drug: placebo to match tegobuvir 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

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01435226

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Sponsors and Collaborators

Gilead Sciences

Investigators


Study Director:	John McNally, PhD	Gilead Sciences

More Information

No publications provided


Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01435226 History of Changes
Other Study ID Numbers:	GS-US-248-0131
Study First Received:	September 13, 2011
Last Updated:	November 22, 2013
Health Authority:	United States: Food and Drug Administration

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 Digestive System Diseases Enterovirus Infections Flaviviridae Infections Hepatitis, Chronic Hepatitis, Viral, Human Liver Diseases	Picornaviridae Infections RNA Virus Infections Virus Diseases Ribavirin Anti-Infective Agents Antimetabolites Antiviral Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015