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
  Purpose

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.


Condition Intervention Phase
HCV Infection
Drug: GS-9256
Drug: GS-9190
Drug: Ribavirin
Drug: Peginterferon alfa-2a
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 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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Plasma pharmacokinetics [ Time Frame: Throughout Day 28 ] [ Designated as safety issue: No ]
  • Viral resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: February 2010
Study Completion Date: January 2012
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: GS-9256
75 mg BID x 28 days
Drug: GS-9190
40 mg BID x 28 days
Experimental: Arm 2 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
Experimental: Arm 3 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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01072695

Locations
Belgium
Brussels, Belgium, 1200
Bruxelles, Belgium, 1070
France
Clichy, France, 92110
La Tronche, France, 38700
Paris, France, 75475
Germany
Duesseldorf, Germany, 40237
Frankfurt, Germany, 60590
Hamburg, Germany, 20099
Hannover, Germany, 30625
Wurzburg, Germany, 97080
United Kingdom
London, United Kingdom, E1 2AT
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Juan Betular Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01072695     History of Changes
Other Study ID Numbers: GS-US-196-0112
Study First Received: February 19, 2010
Last Updated: May 30, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Federal Agency for Medicinal Products and Health Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:
Hepatitis C
HCV
GS-9256
GS-9190
Genotype 1

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

ClinicalTrials.gov processed this record on July 26, 2014