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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

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ClinicalTrials.gov Identifier: NCT01435226
Recruitment Status : Completed
First Posted : September 16, 2011
Last Update Posted : December 17, 2013
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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Brief Summary:
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 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 Design
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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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

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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

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


  Show 51 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John McNally, PhD Gilead Sciences
More Information
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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