GS 5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) in Chronic Genotype 1 Hepatitis C Virus (HCV) Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01353248
First received: April 22, 2011
Last updated: November 26, 2013
Last verified: November 2013
  Purpose

The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: GS-5885
Drug: Tegobuvir
Drug: GS-9451
Drug: ribavirin tablet
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Open-Label Study of GS-5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) to Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Sustained virologic response (SVR) [ Time Frame: 24 weeks of off-treatment follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability [ Time Frame: through 24 weeks of off-treatment follow-up ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of 30 mg or 90 mg GS-5885 when given with GS-9451, Tegobuvir and RBV for 12 or 24 weeks. Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group.

  • HCV RNA < Lower Limit Of Quantification [ Time Frame: Weeks 1, 2, 4, 12 and 24 ] [ Designated as safety issue: No ]
    To evaluate the antiviral efficacy at Weeks 1, 2, 4, 12 and 24, as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse.

  • Rescue Therapy Substudy SVR [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    To evaluate the antiviral efficacy (as defined by SVR) of the addition of pegylated interferon (PEG) for 24 weeks to GS-5885, GS-9451, tegobuvir and RBV in subjects who experience viral breakthrough on treatment.

  • Emergence of viral resistance [ Time Frame: 12 or 24 weeks ] [ Designated as safety issue: No ]
    To evaluate the emergence of viral resistance during treatment with GS-9451, Tegobuvir and RBV when given with 30 mg or 90 mg GS-5885 for 12 or 24 weeks.

  • Viral dynamics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV [ Time Frame: Through Week 2 of therapy ] [ Designated as safety issue: No ]
    HCV RNA levels, pharmacokinetics and viral sequencing

  • Pharmacokinetics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV [ Time Frame: Through Week 2 of therapy ] [ Designated as safety issue: No ]

    Pharmacokinetics (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed

    and summarized for GS-5885, GS-9451 and Tegobuvir using descriptive statistics (e.g.,

    sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation,

    median, minimum, and maximum). Plasma concentrations of the study drug over time will be

    summarized using descriptive statistics



Enrollment: 141
Study Start Date: May 2011
Study Completion Date: March 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 24 weeks.
Drug: GS-5885
tablet, 30 mg QD
Drug: Tegobuvir
capsule, 30 mg BID
Drug: GS-9451
tablet, 200 mg QD
Drug: ribavirin tablet
(weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Active Comparator: Arm 2
GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 12 or 24 weeks.
Drug: Tegobuvir
capsule, 30 mg BID
Drug: GS-9451
tablet, 200 mg QD
Drug: ribavirin tablet
(weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Drug: GS-5885
tablet, 90 mg QD

  Eligibility

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

Inclusion Criteria:

  • Adult subjects 18 to 70 years of age
  • Chronic HCV infection for at least 6 months prior to Baseline (Day 1)
  • Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis
  • Monoinfection with HCV genotype 1a or 1b
  • HCV treatment-naïve
  • Body mass index (BMI) between 18 and 36 kg/m2
  • Creatinine clearance ≥ 50 mL/min
  • Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male.
  • Screening laboratory values within defined thresholds

Exclusion Criteria:

  • Autoimmune disease
  • Decompensated liver disease or cirrhosis
  • Poorly controlled diabetes mellitus
  • Severe psychiatric illness
  • Severe chronic obstructive pulmonary disease (COPD)
  • Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
  • Suspicion of hepatocellular carcinoma or other malignancy (with exception of certain skin cancers)
  • History of hemoglobinopathy
  • Known retinal disease
  • Subjects who are immunosuppressed
  • Subjects with known, current use of amphetamines, cocaine, opiates (i.e., morphine, heroin), methadone, or ongoing alcohol abuse
  • Subjects must have no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant electrocardiogram (ECG) abnormalities at screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01353248

  Show 43 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Benedetta Massetto, MD, PhD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01353248     History of Changes
Other Study ID Numbers: GS-US-248-0120
Study First Received: April 22, 2011
Last Updated: November 26, 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
HCV RNA
Polymerase inhibitor
Protease inhibitor
Treatment naïve
GS-5885
GS-9451
Tegobuvir

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 15, 2014