Trial record 1 of 1 for:    GS-US-248-0131
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GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01435226
First received: September 13, 2011
Last updated: November 22, 2013
Last verified: November 2013
  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:


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

  Show 51 Study Locations
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
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Ribavirin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 22, 2014