Brief Summary
This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared with GS-5885, GS-9451 with Tegobuvir or RBV in Treatment-Experienced Subjects with Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection.
Brief Title
GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hepatitis C, Chronic
Eligibility Criteria
Inclusion Criteria:
* Age ≥18 years with chronic HCV infection
* Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
* Monoinfection with HCV genotype (GT) 1a or 1b
* HCV RNA ≥ 104 IU/mL at screening
* Prior treatment and adherence with one course of pegylated interferon alfa and RBV
* The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
* Body mass index (BMI) 18-40 kg/m2 inclusive
* Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)
≤ 450 msec for males and ≤ 470 msec for females.
* Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.
Exclusion Criteria:
* Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
* History of significant cardiac disease
* Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
* Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
* Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.
* Age ≥18 years with chronic HCV infection
* Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
* Monoinfection with HCV genotype (GT) 1a or 1b
* HCV RNA ≥ 104 IU/mL at screening
* Prior treatment and adherence with one course of pegylated interferon alfa and RBV
* The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
* Body mass index (BMI) 18-40 kg/m2 inclusive
* Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)
≤ 450 msec for males and ≤ 470 msec for females.
* Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.
Exclusion Criteria:
* Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
* History of significant cardiac disease
* Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
* Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
* Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.
Inclusion Criteria
Inclusion Criteria:
* Age ≥18 years with chronic HCV infection
* Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
* Monoinfection with HCV genotype (GT) 1a or 1b
* HCV RNA ≥ 104 IU/mL at screening
* Prior treatment and adherence with one course of pegylated interferon alfa and RBV
* The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
* Body mass index (BMI) 18-40 kg/m2 inclusive
* Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)
≤ 450 msec for males and ≤ 470 msec for females.
* Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.
* Age ≥18 years with chronic HCV infection
* Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
* Monoinfection with HCV genotype (GT) 1a or 1b
* HCV RNA ≥ 104 IU/mL at screening
* Prior treatment and adherence with one course of pegylated interferon alfa and RBV
* The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
* Body mass index (BMI) 18-40 kg/m2 inclusive
* Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)
≤ 450 msec for males and ≤ 470 msec for females.
* Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.
Gender
All
Gender Based
false
Keywords
Hepatitis C
HCV
Rapid Virologic Response
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
Tegobuvir
Treatment Experienced
HCV RNA
Polymerase inhibitor
Protease inhibitor
Interferon intolerant
Interferon ineligible
GS-9190
GS-9451
GS-5885
Chronic Genotype 1a or 1b
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01435226
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-248-0131
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared With GS-5885, GS-9451 With Tegobuvir or RBV in Treatment-Experienced Subjects With Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection
Primary Outcomes
Outcome Description
To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin.
Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.
Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.
Outcome Measure
Safety and Tolerability
Outcome Time Frame
24 weeks
Outcome Description
To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA \< lower limit of quantitation \[LLoQ\] 24 weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and RBV compared with GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and RBV in treatment-experienced subjects with chronic genotype 1a or 1b HCV infection
Outcome Measure
Antiviral Activity
Outcome Time Frame
24 weeks
Secondary Outcomes
Outcome Description
To characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 10 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir.
Outcome Time Frame
10 days
Outcome Measure
Viral Dynamics
Outcome Description
To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau and T ½
Outcome Time Frame
predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
Outcome Measure
Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics
Outcome Description
To evaluate the antiviral efficacy (as defined by SVR) of adding pegylated interferon alfa-2a (PEG) and RBV (Arm 2 only) for 24-48 weeks to the original treatment regimen in subjects who experience viral breakthrough or relapse and enter the Rescue Therapy Substudy
Outcome Time Frame
24-48 weeks
Outcome Measure
Antiviral Efficacy
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Paul Gaglio
Investigator Email
PGAGLIO@montefiore.org
Investigator Phone