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

This study has been completed.
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01439373
First received: July 7, 2011
Last updated: November 15, 2012
Last verified: June 2012
  Purpose

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).


Condition Intervention Phase
Hepatitis C, Chronic
Drug: GSK2336805
Drug: Pegylated interferon alfa-2a
Drug: Ribavirin
Drug: GSK2336805 Matching Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double-Blind, Randomized, Placebo-Controlled Study to Assess Safety, Efficacy, and Pharmacokinetics (PK) of GSK2336805 in Combination With Peginterferon and Ribavirin in Treatment-naive Chronic Hepatitis C Subjects With Hepatitis C Virus Genotypes 1 or 4

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety/tolerability of GSK2336805 in comparison with placebo. [ Time Frame: 28-day treatment period ] [ Designated as safety issue: Yes ]
    Measured by the nature and frequency of AEs and absolute values and changes over time from predose values for hematology, clinical chemistry, urinalysis, vital signs, and ECG parameters.

  • HCV viral load reduction from baseline [ Time Frame: 28-day treatment period ] [ Designated as safety issue: No ]
    HCV viral load reduction from baseline during 24 hours following a single dose of GSK2336805 in comparison with placebo and proportion of subjects achieving rapid virological response, defined as the proportion of subjects below the assay lower limit of detection after 4 weeks of treatment (Day 28) in comparison with placebo.


Secondary Outcome Measures:
  • Composite of pharmacokinetics, Day 1 [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, 24 hours post-dose ] [ Designated as safety issue: No ]
    Area under the concentration-time curve (AUC), maximum plasma concentration (Cmax), Time of maximal plasma concentration (Tmax)

  • Composite of pharmacokinetics, Days 7, 14, 21 [ Time Frame: Post-dose ] [ Designated as safety issue: No ]
    Area under the concentration-time curve (AUC), maximum plasma concentration (Cmax), Time of maximal plasma concentration (Tmax)

  • Composite of pharmacokinetics, Day 28 [ Time Frame: Pre-dose, 2-4 hours post-dose ] [ Designated as safety issue: No ]
    Area under the concentration-time curve (AUC), maximum plasma concentration (Cmax), Time of maximal plasma concentration (Tmax)


Enrollment: 17
Study Start Date: July 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2336805
Study Part 1
Drug: GSK2336805
Active Investigational Drug
Placebo Comparator: Placebo
Study Part 1
Drug: GSK2336805 Matching Placebo
Placebo of Investigational Drug
Other Name: Placebo
Experimental: GSK2336805 + pegylated interferon alfa-2a + ribavrin
Study Part 2
Drug: GSK2336805
Active Investigational Drug
Drug: Pegylated interferon alfa-2a
Standard of Care drug
Other Name: Pegasys
Drug: Ribavirin
Standard of Care drug
Active Comparator: Placebo + pegylated interferon alfa-2a + ribavirin
Study Part 2
Drug: Pegylated interferon alfa-2a
Standard of Care drug
Other Name: Pegasys
Drug: Ribavirin
Standard of Care drug
Drug: GSK2336805 Matching Placebo
Placebo of Investigational Drug
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key 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

Key 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01439373

Locations
United States, California
GSK Investigational Site
Anaheim, California, United States, 92801
GSK Investigational Site
Chula Vista, California, United States, 91911
GSK Investigational Site
Coronado, California, United States, 92118
GSK Investigational Site
La Mesa, California, United States, 91942
GSK Investigational Site
Oceanside, California, United States, 92056
United States, Florida
GSK Investigational Site
Miramar, Florida, United States, 33025
United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89109
United States, Oklahoma
GSK Investigational Site
Tulsa, Oklahoma, United States, 74104
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77004
Puerto Rico
GSK Investigational Site
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
GlaxoSmithKline
PPD
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01439373     History of Changes
Other Study ID Numbers: 115519
Study First Received: July 7, 2011
Last Updated: November 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
chronic hepatitis C
NS5A inhibitor
ribavirin
pegylated interferon
GSK2336805

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferon-alpha
Interferons
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014