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
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

  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 July 22, 2014