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

ClinicalTrials.gov processed this record on October 23, 2014