A Study of Response-Guided Duration of Combination Therapy With GS-9190, GS-9256, Pegasys® and Copegus® in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01225380
First received: October 18, 2010
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of response-guided duration of therapy with GS-9190 and GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®). Additionally, the efficacy and safety of 24 weeks of GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) will be evaluated.


Condition Intervention Phase
Chronic Hepatitis C Infection
Drug: GS-9190
Drug: GS-9256
Biological: Pegasys®
Drug: Copegus®
Drug: GS-9190 placebo
Drug: GS-9256 placebo
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 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating 16 and 24 Weeks of Response Guided Therapy With GS-9190, GS-9256, Ribavirin (Copegus®) and Peginterferon Alfa 2a (Pegasys®) in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS-US-196-0123)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

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

Secondary Outcome Measures:
  • Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events [ Time Frame: Through up to 48 weeks treatment period and 24 weeks of off-treatment follow-up ] [ Designated as safety issue: Yes ]
  • Emergence of viral resistance following initiation of therapy with GS-9190 and GS-9256 [ Time Frame: Through up to 48 weeks treatment period, 24 weeks of off-treatment follow-up, and up to 48 weeks of follow-up in the Resistance Registry Substudy ] [ Designated as safety issue: No ]
  • Viral dynamics and steady state pharmacokinetics of GS-9190 and GS-9256 when administered in combination with PEG and RBV; measured by HCV RNA levels and plasma concentrations of GS-9190 and GS-9256 over time [ Time Frame: Through Week 4 of therapy ] [ Designated as safety issue: No ]
  • Long-term assessment of plasma HCV RNA in subjects who achieve SVR [ Time Frame: 36 months following Week 72 ] [ Designated as safety issue: No ]
    Plasma HCV RNA will be measured at approximately 6, 12, 24, and 36 months after Week 72.


Enrollment: 324
Study Start Date: October 2010
Study Completion Date: September 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
GS-9190 and GS-9256 in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
Drug: GS-9190
GS-9190 capsule, 20 mg BID, 16 or 24 weeks
Drug: GS-9256
GS-9256 capsule, 150 mg BID, 16 or 24 weeks
Biological: Pegasys®
peginterferon alfa-2a, (solution for injection) 180 µg/week, up to 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), up to 48 weeks
Experimental: Arm 2
GS-9256 (active) and placebo matching GS-9190 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
Drug: GS-9190 placebo
placebo matching GS-9190 capsule BID, 24 weeks
Drug: GS-9256
GS-9256 capsule, 150 mg BID, 24 weeks
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week, up to 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), up to 48 weeks
Placebo Comparator: Arm 3
Placebo matching GS-9190 and placebo matching GS-9256 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration
Drug: GS-9190 placebo
placebo matching GS-9190 capsule BID, 24 weeks
Drug: GS-9256 placebo
placebo matching GS-9256 capsule BID, 24 weeks
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week, 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), 48 weeks

  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 for ALT, AST, leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH), potassium, magnesium

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 who are on or are expected to be on a potent cytochrome P450 (CYP) 3A4 or Pgp inhibitor, or a QT prolonging medication within 2 weeks of Baseline (Day 1) or during the study
  • 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: NCT01225380

  Show 114 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Bittoo Kanwar Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01225380     History of Changes
Other Study ID Numbers: GS-US-196-0123
Study First Received: October 18, 2010
Last Updated: December 20, 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-9190
GS-9256

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

ClinicalTrials.gov processed this record on April 16, 2014