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A Study of Response-Guided Duration of Combination Therapy With GS-9451, Pegasys® and Copegus® With and Without Tegobuvir (GS-9190) in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01271790
First received: January 5, 2011
Last updated: March 1, 2013
Last verified: March 2013
History of Changes
  Purpose

This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of a 4-drug regimen with GS-9451 and Tegobuvir and 24 weeks of a 3-drug regimen of GS-9451 without Tegobuvir, all with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®).


Condition Intervention Phase
Hepatitis C, Chronic
 Drug: Tegobuvir (GS-9190)
Drug: GS-9451
Biological: Pegasys®
Drug: Copegus®
Drug: Tegobuvir placebo
Drug: GS-9451 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 Four-Drug Regimen and 24 Weeks of a Three-Drug Regimen of GS-9451, Peginterferon Alfa 2a (PEG, Pegasys®) and Ribavirin (RBV, Copegus®) With and Without Tegobuvir (GS-9190) Followed by Response Guided PEG and RBV in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS US 196 0140

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

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


Secondary Outcome Measures:
  • Safety and tolerability of therapy [ Time Frame: Through treatment period and 24 weeks of off-treatment follow-up ] [ Designated as safety issue: Yes ]
    Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events

  • Emergence of viral resistance following initiation of therapy with GS 9190 and GS 9451 [ Time Frame: Through 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 [ Time Frame: Through Week 4 of therapy ] [ Designated as safety issue: No ]
    Viral dynamics and steady state pharmacokinetics of GS 9190 and GS 9451 when administered in combination with PEG and RBV; measured by HCV RNA levels and plasma concentrations of GS-9190 and GS-9451 over time

  • Durability of response in subjects who achieve SVR [ Time Frame: 36 months following Week 72 ] [ Designated as safety issue: No ]

Estimated Enrollment: 320
Study Start Date: October 2010
Estimated Study Completion Date: January 2017
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
GS-9451 and Tegobuvir (GS-9190) 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: Tegobuvir (GS-9190)
Tegobuvir (GS-9190) capsule, 30 mg BID
Drug: GS-9451
GS-9451 tablet, 200 mg QD
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week
Drug: Copegus®
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Active Comparator: Arm 2
GS-9451 (active) and Tegobuvir (GS-9190) placebo 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-9451
GS-9451 tablet, 200 mg QD
Drug: Tegobuvir placebo
placebo matching Tegobuvir (GS-9190) capsule BID
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week
Drug: Copegus®
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Placebo Comparator: Arm 3
Placebo matching Tegobuvir (GS-9190) and GS-9451 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total duration
 Drug: Tegobuvir placebo
placebo matching Tegobuvir (GS-9190) capsule BID
Drug: GS-9451 placebo
placebo matching GS-9451 tablet QD
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week
Drug: Copegus®
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet

  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: NCT01271790

  Show 144 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: NCT01271790     History of Changes
Other Study ID Numbers: GS-US-196-0140
Study First Received: January 5, 2011
Last Updated: March 1, 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-9451

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
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013