GS-5885, GS-9451 With Peginterferon Alfa 2a (PEG) and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 Hep C Virus Infection and IL28B CC Genotype

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01384383
First received: June 22, 2011
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

This is a Phase 2, randomized, open-label exploratory study that will examine the antiviral efficacy, safety, and tolerability of Response guided treatment (RGT) with GS-5885 + GS-9451 + PEG/RBV (6 or 12 weeks), or Peginterferon Alfa 2a (PEG)/Ribavirin (RBV)alone (24 weeks) in treatment naïve subjects with chronic Hep C (HCV) infection with genotype (GT) 1 and IL28B CC genotype.


Condition Intervention Phase
Chronic Hepatitis C
Drug: GS-5885
Drug: GS-9451
Drug: RBV
Drug: PEG
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Open-Label, Exploratory Trial of GS-5885, GS-9451 With Peginterferon Alfa 2a and Ribavirin (RBV) in Treatment-Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection and IL28B CC Genotype

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Sustained virologic response (SVR) [ Time Frame: 30 , 36 or 48 weeks ] [ Designated as safety issue: No ]
    Sustained virologic response (SVR, defined as plasma HCV RNA < lower limit of quantification [LLoQ] at 24 weeks after treatment cessation) following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 or 12 weeks, or PEG/RBV for 24 weeks in IL28B CC subjects.


Secondary Outcome Measures:
  • Safety and tolerability of therapy [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    Safety and tolerability of the therapy is measured by frequency of laboratory abnormalities , reported adverse events and discontinuations due to adverse events.

  • Virologic response [ Time Frame: Weeks 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
    Virologic response at Weeks 2, 4, 6, 8, 10, and 12 (depending on treatment arm) as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse

  • Compare SVR [ Time Frame: Weeks 30 and 36 ] [ Designated as safety issue: No ]
    Compare SVR following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 weeks versus 12 weeks.

  • Viral resistance [ Time Frame: Up to 96 Weeks ] [ Designated as safety issue: No ]
    Characterize viral resistance to GS-5885 and GS-9451 when administered in combination with PEG/RBV


Enrollment: 248
Study Start Date: August 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks.
Drug: GS-5885
GS-5885 30 mg tablet administered orally once daily
Drug: GS-9451
GS-9451 200 mg tablet administered orally once daily
Drug: RBV
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
Experimental: Arm 2
Response-Guided Therapy with PEG and RBV for 24 weeks.
Drug: RBV
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
Drug: PEG
Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection

  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 (≤ 3 years prior to screening) indicating the absence of cirrhosis. Alternatively a non-invasive alternative to liver biopsy (such as FibroTest, FibroScan, or Acoustic Radiation Force Impulse imaging) within 6 months of Screening in countries where allowed
  • Monoinfection with HCV genotype 1a or 1b
  • HCV RNA > 10^4 IU/mL at Screening
  • IL28B CC genotype
  • HCV treatment naïve
  • Candidate for PEG/RBV therapy
  • Body mass index (BMI) between 18 and 36 kg/m2
  • Creatinine clearance >= 50 mL/min
  • Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline

Exclusion Criteria:

  • Exceed defined thresholds for key laboratory parameters at Screening
  • 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 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. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study
  • Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment
  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: NCT01384383

  Show 55 Study Locations
Sponsors and Collaborators
Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01384383     History of Changes
Other Study ID Numbers: GS-US-248-0121
Study First Received: June 22, 2011
Last Updated: January 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Chronic Hepatitis C
IL28B CC Genotype
Treatment naive
Peginterferon α-2a (PEG)
Genotype 1a/b
GS 9451
GS 5885
Ribavirin (RBV)
HCV NS5A inhibitor
HCV NS3 protease inhibitor

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Virus Diseases
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014