GS 5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) in Chronic Genotype 1 Hepatitis C Virus (HCV) Infection

Hepatitis C, Chronic Clinical Trial

Official title:

A Phase 2 Randomized, Open-Label Study of GS-5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) to Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01353248
• Other study ID #: GS-US-248-0120
• Status: Completed
• Phase: Phase 2
• First received: April 22, 2011
• Last updated: November 26, 2013
• Start date: May 2011
• Est. completion date: March 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

The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 141
• Est. completion date: March 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Adult subjects 18 to 70 years of age

• Chronic HCV infection for at least 6 months prior to Baseline (Day 1)

• Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis

• Monoinfection with HCV genotype 1a or 1b

• HCV treatment-naïve

• Body mass index (BMI) between 18 and 36 kg/m2

• Creatinine clearance = 50 mL/min

• Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male.

• Screening laboratory values within defined thresholds

Exclusion Criteria:

• Autoimmune disease

• Decompensated liver disease or cirrhosis

• Poorly controlled diabetes mellitus

• Severe psychiatric illness

• Severe chronic obstructive pulmonary disease (COPD)

• Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype

• Suspicion of hepatocellular carcinoma or other malignancy (with exception of certain skin cancers)

• History of hemoglobinopathy

• Known retinal disease

• Subjects who are immunosuppressed

• Subjects with known, current use of amphetamines, cocaine, opiates (i.e., morphine, heroin), methadone, or ongoing alcohol abuse

• Subjects must have no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant electrocardiogram (ECG) abnormalities at screening

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• GS-5885
tablet, 30 mg QD
• Tegobuvir
capsule, 30 mg BID
• GS-9451
tablet, 200 mg QD
• ribavirin tablet
(weight based: 1000 mg/day <75 kg; 1200 mg/day = 75 kg) divided twice daily (BID)
• GS-5885
tablet, 90 mg QD

Locations

Country	Name	City	State
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
United States	University of New Mexico	Albuquerque	New Mexico
United States	Advanced Clinical Research Institute	Anaheim	California
United States	Birmingham Gastroenterology Associates, P.C.	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Bach and Godofsky Infectious Diseases	Bradenton	Florida
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Southern California Liver Centers	Coronado	California
United States	Baylor University Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Digestive Health Specialists of the Southeast	Dothan	Alabama
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital - Center for Liver Diseases	Falls Church	Virginia
United States	UCSF Fresno Medical Education Program (MEP)	Fresno	California
United States	University of Florida - Gainesville	Gainesville	Florida
United States	Gastro One	Germantown	Tennessee
United States	Memphis Gastroenterology Group	Germantown	Tennessee
United States	Research Specialists of Texas	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Gastrointestinal Associates, PA	Jackson	Mississippi
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	Johns Hopkins University	Lutherville	Maryland
United States	Gastrointestinal Specialists of Georgia PC	Marietta	Georgia
United States	University of Miami School of Medicine	Miami	Florida
United States	Columbia Medical Group, The Frist Clinic	Nashville	Tennessee
United States	Nashville Gastrointestinal Specialists, Inc	Nashville	Tennessee
United States	Mount Sinai Medical Center	New York	New York
United States	Liver Institute of Virginia, Bon Secours Health System	Newport News	Virginia
United States	Private Practice	Opelousas	Louisiana
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Stanford University School of Medicine	Palo Alto	California
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Lifetree Clinical Research, LC	Salt Lake City	Utah
United States	Alamo Medical Research	San Antonio	Texas
United States	Kaiser Permanente	San Diego	California
United States	University of California San Diego	San Diego	California
United States	UCSF	San Francisco	California
United States	Options Health Research, LLC	Tulsa	Oklahoma
United States	Walter Reed Army Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response (SVR)		24 weeks of off-treatment follow-up	No
Secondary	Safety and tolerability	To evaluate the safety and tolerability of 30 mg or 90 mg GS-5885 when given with GS-9451, Tegobuvir and RBV for 12 or 24 weeks. Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group.	through 24 weeks of off-treatment follow-up	Yes
Secondary	HCV RNA < Lower Limit Of Quantification	To evaluate the antiviral efficacy at Weeks 1, 2, 4, 12 and 24, as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse.	Weeks 1, 2, 4, 12 and 24	No
Secondary	Rescue Therapy Substudy SVR	To evaluate the antiviral efficacy (as defined by SVR) of the addition of pegylated interferon (PEG) for 24 weeks to GS-5885, GS-9451, tegobuvir and RBV in subjects who experience viral breakthrough on treatment.	24 Weeks	No
Secondary	Emergence of viral resistance	To evaluate the emergence of viral resistance during treatment with GS-9451, Tegobuvir and RBV when given with 30 mg or 90 mg GS-5885 for 12 or 24 weeks.	12 or 24 weeks	No
Secondary	Viral dynamics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV	HCV RNA levels, pharmacokinetics and viral sequencing	Through Week 2 of therapy	No
Secondary	Pharmacokinetics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV	Pharmacokinetics (Cmax, Tmax, Clast, Tlast, Ctau, ?z, AUCtau, and T½) will be listed; and summarized for GS-5885, GS-9451 and Tegobuvir using descriptive statistics (e.g.,; sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation,; median, minimum, and maximum). Plasma concentrations of the study drug over time will be; summarized using descriptive statistics	Through Week 2 of therapy	No