NCT01648140

Dose Ranging of GSK2336805 in Combination Therapy

A Phase II Multicenter, Parallel-Group, Randomized, Dose-Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Following 12 Weeks of Oral Administration of GSK2336805 With Pegylated Interferon and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 or 4 Hepatitis C Infection

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 286 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

GSK2336805 is a novel hepatitis C virus (HCV) non-structural 5A (NS5A) inhibitor being developed for the treatment of chronic HCV infection. This Phase II, multicenter, parallel-group, randomized, dose-ranging study will assess the safety and tolerability, antiviral activity, and pharmacokinetics of GSK2336805 at 2 dose levels (40 and 60 mg) in combination with pegylated interferon alfa-2a (PEG) and ribavirin (RIBA) in approximately 100 treatment-naïve subjects with chronic genotype 1 HCV infection. In a separate nonrandomized single-arm cohort, up to 15 treatment-naïve subjects with genotype 4 chronic HCV infection will be enrolled in parallel at the dose level of 60 mg of GSK2336805.

Detailed description

Subjects with chronic genotype 1 hepatitis C virus (HCV) infection will be randomly assigned on a 2:2:1 basis to 1 of 3 treatment arms: T40 (GSK2336805 40 mg and PEG + RIBA) or T60 (GSK2336805 60 mg and PEG + RIBA) or PEG + RIBA and telaprevir (PRT). Randomization will be stratified by interleukin 28B (IL28B) rs12979860 status (C/C versus carriage of the T allele), HCV genotype (1a vs. 1b), and plasma HCV Ribonucleic Acid (RNA) (\<800,000 IU/mL versus ≥800,000 IU/mL). An additional nonrandomized single-arm cohort of subjects with chronic genotype 4 HCV infection will be enrolled in parallel. A maximum of 15 genotype 4 subjects will receive GSK2336805 60 mg and PEG + RIBA. The purpose of this cohort is to further characterize the antiviral activity of GSK2336805 in subjects with chronic genotype 4 HCV infection. The schedule of assessments for the genotype 4 subjects will be the same as for the genotype 1 subjects. Recruitment of the genotype 4 subjects may be terminated when the target sample of genotype 1 subjects have been randomized. Subjects in a GSK2336805 treatment arm who achieve extended rapid virologic response (eRVR) will receive a total of 24 weeks of therapy (12 weeks GSK2336805 in combination with PEG + RIBA followed by 12 weeks PEG + RIBA). Subjects who are HCV detectable at Week 4 and then undetectable at Week 12 will receive a total of 48 weeks of therapy (12 weeks GSK2336805 in combination with PEG + RIBA followed by 36 weeks PEG + RIBA). Subjects in the telaprevir treatment control arm will be managed according to the current product label for treatment-naïve subjects. Subjects who complete treatment will undergo follow-up monitoring for 24 weeks after completion of therapy. At the end of the 24-week follow-up visit, subjects will have completed their participation in the study. The total duration of the study will be 48 weeks for subjects who achieve eRVR at Week 12 and up to 72 weeks for subjects who do not achieve eRVR at Week 12.

Conditions

• Hepatitis C, Chronic

Interventions

Type	Name	Description
DRUG	GSK2336805 40 mg	20 mg tablet, round, 10-mm diameter, white to off-white, no markings
DRUG	GSK2336805 60 mg	30 mg tablet, round, 10-mm diameter, white to off-white, no markings
DRUG	Pegylated interferon alpha-2a	180 microgram per 0.5 mL prefilled syringe for single use
DRUG	Ribavirin	200-mg tablet, capsule-shaped, light blue, film-coated, and debossed with "200" on 1 side and the logo "3RP" on the other side
DRUG	Telaprevir	375 mg film-coated tablet

Timeline

• Start date: 2012-08-01
• Primary completion: 2014-07-01
• Completion: 2014-07-16
• First posted: 2012-07-24
• Last updated: 2017-06-02
• Results posted: 2017-06-02

Locations

34 sites across 6 countries: United States, Belgium, Bulgaria, France, Germany, Puerto Rico