Efficacy and Safety Study of GS-9256 and GS-9190 Alone and in Combination With Ribavirin for 28 Days in Patients With Chronic Hepatitis C Virus Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01072695
First received: February 19, 2010
Last updated: May 30, 2012
Last verified: May 2012

February 19, 2010
May 30, 2012
February 2010
October 2010   (final data collection date for primary outcome measure)
  • Percentage of subjects achieving rapid virologic response (RVR) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • AEs, physical examination and clinical laboratory test findings, vital signs, ECGs [ Time Frame: Throughout first six weeks of study ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01072695 on ClinicalTrials.gov Archive Site
  • Plasma pharmacokinetics [ Time Frame: Throughout Day 28 ] [ Designated as safety issue: No ]
  • Viral resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Efficacy and Safety Study of GS-9256 and GS-9190 Alone and in Combination With Ribavirin for 28 Days in Patients With Chronic Hepatitis C Virus Infection
A Phase 2, Randomized, Open-Label Trial of GS-9256 Plus GS-9190 Alone and in Combination With Ribavirin for 28 Days in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS-US-196-0112)

This a phase 2, randomized, open-label trial of GS-9256 plus GS-9190, two oral anti HCV drugs, for 28 days with and without ribavirin (RIBA) and with pegylated interferon (PEG)/RIBA in adults with chronic Hepatitis C virus (HCV). In Part A, approximately thirty (30) subjects 18-70 years of age who meet study entry criteria will be randomized (in other words, selected at random, like flipping a coin) to one of the two treatment groups (GS-9256 plus GS-9190 or GS-9256 plus GS-9190 plus RIBA). In Part B, an additional fifteen (15) subjects will receive 75 mg GS-9256 BID plus 40 mg GS-9190 BID in combination with PEG/RIBA. After the 28-day treatment period, subjects will receive PEG/RIBA as standard of care (SOC).

Following randomization, subjects will return for a Baseline (Day 1) visit, at which time study medication will be dispensed and subjects will enter a 28 day treatment phase. During the treatment phase, subjects will receive oral study drugs twice daily for 28 days and PEG once weekly for Part B. Subjects then receive PEG/RIBA as local SOC starting on Day 28 (not provided as part of the study). Following completion of the 28-day treatment phase, subjects will be followed for approximately 72 weeks.

GS-9256 (an HCV NS3 protease inhibitor) plus GS-9190 (non-nucleoside HCV NS5B inhibitor) will be administered for 28 days with and without RIBA (weight-based dosing) and with PEG/RIBA in treatment-naïve subjects with chronic genotype 1 HCV infection. In Part A, thirty (30) subjects with genotype 1 will be randomized to 75 mg GS-9256 BID plus 40 mg GS-9190 BID or 75 mg GS-9256 BID plus 40 mg GS-9190 BID plus RIBA 1000-1200 mg/day for 28 days. In Part B, an additional fifteen (15) subjects with genotype 1 will receive 75 mg GS-9256 BID plus 40 mg GS-9190 BID in combination with PEG/RIBA for 28 days. After the 28-day treatment period, subjects will receive PEG/RIBA as standard of care (SOC).

In Part A, for any subjects meeting pre-defined, individual, virologic criteria, PEG/RIBA standard of care will be started prior to Day 28.

Both PEG and RIBA will be administered at their currently approved dosages for treatment of HCV infection in accordance with appropriate labeling. Subjects will be monitored for safety (including ECG monitoring), antiviral activity, pharmacokinetics, and resistance 2-3 times weekly through Day 28.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HCV Infection
  • Drug: GS-9256
    75 mg BID x 28 days
  • Drug: GS-9190
    40 mg BID x 28 days
  • Drug: Ribavirin
    1000-1200 mg/day given BID
    Other Name: COPEGUS
  • Drug: Peginterferon alfa-2a
    180 ug q week
    Other Name: Pegasys
  • Experimental: Arm 1
    Interventions:
    • Drug: GS-9256
    • Drug: GS-9190
  • Experimental: Arm 2
    Interventions:
    • Drug: GS-9256
    • Drug: GS-9190
    • Drug: Ribavirin
  • Experimental: Arm 3
    Interventions:
    • Drug: GS-9256
    • Drug: GS-9190
    • Drug: Ribavirin
    • Drug: Peginterferon alfa-2a
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
46
January 2012
October 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adult subjects, ages 18-70
  • Willing able to provide informed consent
  • BMI between 18 and 36 kg/m2 (inclusive)
  • Chronic HCV infection, genotype 1
  • HCV RNA >/= 3 log, but < 7.2 log10 IU/ml at screen
  • Liver biopsy, FibroTest, or FibroScan indicating absence of cirrhosis
  • HCV treatment naïve with imminent plans to start treatment with PEG/RIBA
  • QTcF </= 450 msec at screen
  • ALT, AST, GGT < 5 X ULN at the screening visit
  • Creatinine clearance >= 50 mL/min
  • Absolute neutrophil count >= 1500/mm3
  • Hemoglobin >/= 12 g/dL (female), >/= 13 g/dL (male)
  • Males agree to use of effective contraception and refrain from sperm donation
  • Able to comply with dosing instructions and study visits
  • Of generally good health

Exclusion Criteria:

  • Females of child-bearing potential or males with female partners who are pregnant or planning to become pregnant
  • Infection with other HCV genotype or multiple HCV genotypes
  • Poorly controlled diabetes
  • Hemoglobinopathy or known retinal disease
  • History of sarcoidosis or invasive malignancy
  • Untreated or significant psychiatric illness
  • Co-infection with hepatitis B virus or human immunodeficiency virus
  • Chronic use of systemic immunosuppressive agents
  • Autoimmune disorders
  • Severe COPD
  • History of significant cardiac disease
  • Known cirrhosis
  • Non-HCV chronic liver disease
  • Transplantation
  • Suspicion of hepatocellular carcinoma
  • Bilirubin above the normal range or Gilbert's syndrome
  • Decompensated liver disease
  • Clinically significant illness
  • GI disease that could interfere with absorption
  • Acute porphyria
  • Current excessive alcohol ingestion, averaging > 3 drinks/day for females and > 4 drinks/day for males or current binge drinking
  • Positive urine drug screen
  • History of difficult blood collection
  • Significant recent blood loss
  • Prohibited medications, including H2 antagonists, investigational agents
  • Restricted fruits, fruit juices
  • Hypersensitivity
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
France,   Belgium,   United Kingdom,   Germany
 
NCT01072695
GS-US-196-0112
No
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Juan Betular Gilead Sciences
Gilead Sciences
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP