Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects

NCT ID: NCT01439373

Last Updated: 2017-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-07
• Study Completion Date: 2011-12-05

Brief Summary

GSK2336805 is a hepatitis C virus (HCV) NS5A inhibitor being developed for the treatment of chronic hepatitis C (CHC). This study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with chronic hepatitis C (CHC).

Detailed Description

HCV infection is a major public health problem globally and a leading cause of chronic liver disease. New medications are needed that are better tolerated and offer a greater chance of achieving sustained viral clearance compared to currently available therapy. GSK2336805 is a HCV NS5A inhibitor being developed for the treatment of subjects with CHC. This Phase II, double blind, randomized, placebo-controlled study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with CHC. Subjects will be randomly allocated on a 2:1 basis to GSK2336805 or matching placebo and will be stratified by IL28B status and HCV viral genotype (genotype 1 or 4). The study consists of 2 parts. In Part 1, GSK2336805 or matching placebo will be given as single-dose monotherapy (Day 1). In Part 2, GSK2336805 or matching placebo will be co-administered with peginterferon alfa-2a and ribavirin through 4 weeks of treatment (Days 2 to 28). After completion of Part 2, GSK2336805/matching placebo will be discontinued and subjects will be offered continued standard-of-care anti-HCV therapy.

Conditions

Hepatitis C, Chronic

Keywords

chronic hepatitis C; NS5A inhibitor; ribavirin; pegylated interferon; GSK2336805

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GSK2336805

Study Part 1

Group Type: EXPERIMENTAL

GSK2336805

Intervention Type: DRUG

Active Investigational Drug

Placebo

Study Part 1

Group Type: PLACEBO_COMPARATOR

GSK2336805 Matching Placebo

Intervention Type: DRUG

Placebo of Investigational Drug

GSK2336805 + pegylated interferon alfa-2a + ribavrin

Study Part 2

Group Type: EXPERIMENTAL

GSK2336805

Intervention Type: DRUG

Active Investigational Drug

Pegylated interferon alfa-2a

Intervention Type: DRUG

Standard of Care drug

Ribavirin

Intervention Type: DRUG

Standard of Care drug

Placebo + pegylated interferon alfa-2a + ribavirin

Study Part 2

Group Type: ACTIVE_COMPARATOR

Pegylated interferon alfa-2a

Intervention Type: DRUG

Standard of Care drug

Ribavirin

Intervention Type: DRUG

Standard of Care drug

GSK2336805 Matching Placebo

Intervention Type: DRUG

Placebo of Investigational Drug

Interventions

GSK2336805

Active Investigational Drug

Intervention Type: DRUG

Pegylated interferon alfa-2a

Standard of Care drug

Intervention Type: DRUG

Ribavirin

Standard of Care drug

Intervention Type: DRUG

GSK2336805 Matching Placebo

Placebo of Investigational Drug

Intervention Type: DRUG

Other Intervention Names

Pegasys; Placebo

Eligibility Criteria

Inclusion Criteria

• Documented chronic genotype 1 or genotype 4 HCV infection
• Naïve to all HCV antiviral treatment(s)
• Agree to IL28B genotyping
• A body mass index >18 kg/m2 but not exceeding 36 kg/m2
• Liver biopsy obtained within 3 years (36 calendar months) prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic. If no recent (<36 months) liver biopsy is available, a study qualifying biopsy must be performed prior to Baseline (Day 1)
• All fertile males and females must use two forms of effective contraception between them during treatment and during the 24 weeks after treatment ends
• Otherwise healthy as determined by the medical history, physical examination, ECG findings, and clinical laboratory measurements performed at Screening

Exclusion Criteria

• Positive test at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody
• History of any other clinically significant chronic liver disease
• History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease
• Positive results on urine screen for drugs of abuse test at Screening (unless used as medical treatment, e.g., with a prescription)
• History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation program)
• Screening ECG corrected QT interval value greater than 450 ms and/or clinically significant ECG findings
• A personal or family history of Torsade de Pointes findings
• Pregnant or nursing women
• Males with a female partner who is pregnant
• Abnormal hematological and biochemical parameters as specified in the protocol
• History of major organ transplantation with an existing functional graft
• Thyroid dysfunction not adequately controlled
• Subjects with a history of suicide attempt or hospitalization for depression in the past 5 years and/or any current (within 6 months) severe or poorly controlled psychiatric disorder
• History or current evidence of immunologic disorder; pulmonary, cardiac, or pulmonary disease; seizure disorder; cancer or history of malignancy that in the opinion of the investigator makes the subject unsuitable for the study
• Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to first dose administration

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PPD Development, LP

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Anaheim, California, United States

GSK Investigational Site

Chula Vista, California, United States

GSK Investigational Site

Coronado, California, United States

GSK Investigational Site

La Mesa, California, United States

GSK Investigational Site

Oceanside, California, United States

GSK Investigational Site

Miramar, Florida, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Tulsa, Oklahoma, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

Gardner S, Cutrell A, Elko-Simms C, Adkison K, Hamatake R, Walker J, Rodriguez-Torres M, Hong Z. A double-blind, randomized, placebo-controlled study to assess the safety, antiviral activity and pharmacokinetics of GSK2336805 when given as monotherapy and in combination with peginterferon alfa-2a and ribavirin in hepatitis C virus genotype 1-infected treatment-naive subjects. Liver Int. 2014 Jul;34(6):e89-95. doi: 10.1111/liv.12334. Epub 2013 Oct 16.

Reference Type: DERIVED

PMID: 24107072 (View on PubMed)

Other Identifiers

115519

Identifier Type: -

Identifier Source: org_study_id