GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection

Hepatitis C, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01435226
• Other study ID #: GS-US-248-0131
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2011
• Last updated: November 22, 2013
• Start date: September 2011
• Est. completion date: July 2013

Study information

• Verified date: November 2013
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 170
• Est. completion date: July 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• GS-5885
Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD
• GS-9451
Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD
• tegobuvir
tegobuvir 30 mg BID
• placebo to match tegobuvir
tegobuvir placebo BID
• placebo to match RBV
Ribovirin placebo BID
• Ribavirin
Ribavirin (Copegus®) BID (1000 mg for subjects weighing < 75 kg and 1200 mg for subjects weighing = 75 kg) divided BID

Locations

Country	Name	City	State
Germany	Charite - Universitatsmedizin Berlin Campus Virchow-Klinikum	Berlin
Germany	Leber- and Studienzentrum am Checkpoint	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	Center for HIV and Hepatogastroenterology	Düsseldorf
Germany	Klinikum der Johann Wolfgang Goethe Universitaet	Frankfurt
Germany	Medizinische Universitatsklinik	Freiburg
Germany	Universitatsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Klinikum der Universität Heidelberg	Heidelberg
Germany	Gastroenterologisch-Hepatologisches Zentrum Kiel	Kiel
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Johannes Gutenberg University Hospital	Mainz
Germany	Klinikum Innenstadt der LMU Munchen	Muenchen
Germany	Universitätsklinikum Würzburg - Med Klinik und Poliklinik	Würzburg
United States	Advanced Clinical Research Institute, LLC	Anaheim	California
United States	Mercy Medical Center	Baltimore	Maryland
United States	California Liver Institute	Beverly Hills	California
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	SCTI Research Foundation Liver Center	Coronado	California
United States	Southwest Infectious Disease Clinical Research, Inc	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Gastro One	Germantown	Tennessee
United States	The University of Texas Health Sciences Center at Houston	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California, San Diego	La Jolla	California
United States	Lightsource Medical	Los Angeles	California
United States	Johns Hopkins University	Lutherville	Maryland
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	University of Miami, Center for Liver Diseases	Miami	Florida
United States	Mount Sinai School of Medicine	New York	New York
United States	Weill Medical College of Cornell Univeristy	New York	New York
United States	Bon Secours St. Mary's Hospital of Richmond, Inc.	Newport News	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Henry Ford Health System	Novi	Michigan
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University Gastroenterology	Providence	Rhode Island
United States	University of Utah	Salt Lake City	Utah
United States	Alamo Medical Research, Ltd.	San Antonio	Texas
United States	Kaiser Permanente	San Diego	California
United States	Medical Associates Research Group, Inc.	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	San Jose Gastroenterology	San Jose	California
United States	Virginia Mason Medical Center	Seattle	Washington
United States	University of Arizona	Tucson	Arizona
United States	Whitman Walker Clinic	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability	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.	24 weeks	Yes
Primary	Antiviral Activity	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	24 weeks	No
Secondary	Viral Dynamics	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.	10 days	No
Secondary	Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics	To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, ?z, AUCtau and T ½	predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose	No
Secondary	Antiviral Efficacy	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	24-48 weeks	No