GS-5885 Alone or in Combination With GS-9451 With Peginterferon Alfa 2a and Ribavirin in Treatment Chronic Genotype 1 Hepatitis C Virus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01356160
First received: May 2, 2011
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy with GS-5885 Alone or in Combination with GS-9451 with Peginterferon Alfa 2a and Ribavirin in Treatment Naïve Subjects with Chronic Genotype 1 Hepatitis C Virus Infection.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: GS-5885
Drug: GS-9451
Biological: peginterferon alfa-2a
Drug: ribavirin tablet
Drug: GS-9451 Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy With GS-5885 Alone or in Combination With GS-9451 With Peginterferon Alfa 2a and Ribavirin in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • To evaluate the antiviral efficacy of response guided therapy. [ Time Frame: Through 24 weeks post-treatment ] [ Designated as safety issue: No ]
    To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as plasma HCV RNA < Lower Limit of Quantification (LLoQ) at 24 weeks post-treatment) of response guided therapy (RGT) with GS-5885 + GS-9451 + PEG/RBV, or GS-5885 + PEG/RBV.


Secondary Outcome Measures:
  • To evaluate the safety and tolerability of each regimen. [ Time Frame: Through 24 weeks post-treatment ] [ Designated as safety issue: No ]
    The primary safety endpoint is any AE leading to permanent discontinuation of study drugs.

  • To characterize viral dynamics of GS-5885 and GS-9451 when administered with PEG and RBV. [ Time Frame: Through Day 10 on study ] [ Designated as safety issue: No ]
    HCV RNA levels, pharmacokinetics and viral sequencing

  • To characterize the viral resistance to GS-5885 and GS-9451 when administered in combination with PEG and RBV. [ Time Frame: 12 or 24 weeks ] [ Designated as safety issue: No ]
    Plasma samples will be collected and stored at each visit for possible resistance analysis.

  • To characterize steady state pharmacokinetics of GS-5885 and GS-9451 when administered with PEG and RBV. [ Time Frame: Through 48 weeks of treatment ] [ Designated as safety issue: No ]
    Plasma concentrations of the study drug over time will be summarized using descriptive statistics.


Enrollment: 351
Study Start Date: July 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
RGT with GS-5885 30 mg QD + GS-9451 200 mg QD + PEG/RBV
Drug: GS-5885
tablet, 30 mg QD
Drug: GS-9451
tablet, 200 mg QD
Biological: peginterferon alfa-2a
(solution for injection) 180 µg/week
Drug: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Placebo Comparator: Arm 2
RGT with GS-5885 30 mg QD + GS-9451 placebo QD + PEG/RBV
Drug: GS-5885
tablet, 30 mg QD
Biological: peginterferon alfa-2a
(solution for injection) 180 µg/week
Drug: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Drug: GS-9451 Placebo
Placebo to match GS-9451 QD

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females 18-70 years of age
  • Chronic HCV infection
  • Subjects must have liver biopsy results (≤ 2 years prior to Screening) indicating the absence of cirrhosis.
  • Monoinfection with HCV genotype 1
  • HCV RNA > 10^4 IU/mL at Screening
  • HCV treatment naïve
  • Candidate for PEG/RBV therapy
  • Body mass index (BMI) 18-36 kg/m2, inclusive
  • Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline.

Exclusion Criteria:

  • Pregnant female or male with pregnant female partner
  • Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, 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.
  • Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Patients on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening may be included into the study.
  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: NCT01356160

  Show 23 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Chair: Bittoo Kanwar, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01356160     History of Changes
Other Study ID Numbers: GS-US-256-0148
Study First Received: May 2, 2011
Last Updated: January 2, 2014
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 HCV RNA
Protease inhibitor
Treatment naïve
GS-5885
GS-9451

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
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014