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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

Primary Purpose

HCV Infection

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GS-9256
GS-9190
Ribavirin
Peginterferon alfa-2a
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HCV Infection focused on measuring Hepatitis C, HCV, GS-9256, GS-9190, Genotype 1

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm 1

Arm 2

Arm 3

Arm Description

Outcomes

Primary Outcome Measures

Percentage of subjects achieving rapid virologic response (RVR)
AEs, physical examination and clinical laboratory test findings, vital signs, ECGs

Secondary Outcome Measures

Plasma pharmacokinetics
Viral resistance

Full Information

First Posted
February 19, 2010
Last Updated
May 30, 2012
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01072695
Brief Title
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
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HCV Infection
Keywords
Hepatitis C, HCV, GS-9256, GS-9190, Genotype 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Title
Arm 2
Arm Type
Experimental
Arm Title
Arm 3
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GS-9256
Intervention Description
75 mg BID x 28 days
Intervention Type
Drug
Intervention Name(s)
GS-9190
Intervention Description
40 mg BID x 28 days
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
COPEGUS
Intervention Description
1000-1200 mg/day given BID
Intervention Type
Drug
Intervention Name(s)
Peginterferon alfa-2a
Other Intervention Name(s)
Pegasys
Intervention Description
180 ug q week
Primary Outcome Measure Information:
Title
Percentage of subjects achieving rapid virologic response (RVR)
Time Frame
Day 28
Title
AEs, physical examination and clinical laboratory test findings, vital signs, ECGs
Time Frame
Throughout first six weeks of study
Secondary Outcome Measure Information:
Title
Plasma pharmacokinetics
Time Frame
Throughout Day 28
Title
Viral resistance
Time Frame
Throughout study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan Betular
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
City
Clichy
ZIP/Postal Code
92110
Country
France
City
La Tronche
ZIP/Postal Code
38700
Country
France
City
Paris
ZIP/Postal Code
75475
Country
France
City
Duesseldorf
ZIP/Postal Code
40237
Country
Germany
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
City
Hannover
ZIP/Postal Code
30625
Country
Germany
City
Wurzburg
ZIP/Postal Code
97080
Country
Germany
City
London
ZIP/Postal Code
E1 2AT
Country
United Kingdom
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom

12. IPD Sharing Statement

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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

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