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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

July 7, 2011
November 15, 2012
July 2011
December 2011   (final data collection date for primary outcome measure)
  • 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.
Same as current
Complete list of historical versions of study NCT01439373 on ClinicalTrials.gov Archive Site
  • 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)
Same as current
Not Provided
Not Provided
 
Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects
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

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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hepatitis C, Chronic
  • Drug: GSK2336805
    Active Investigational Drug
  • 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
  • Experimental: GSK2336805
    Study Part 1
    Intervention: Drug: GSK2336805
  • Placebo Comparator: Placebo
    Study Part 1
    Intervention: Drug: GSK2336805 Matching Placebo
  • Experimental: GSK2336805 + pegylated interferon alfa-2a + ribavrin
    Study Part 2
    Interventions:
    • Drug: GSK2336805
    • Drug: Pegylated interferon alfa-2a
    • Drug: Ribavirin
  • Active Comparator: Placebo + pegylated interferon alfa-2a + ribavirin
    Study Part 2
    Interventions:
    • Drug: Pegylated interferon alfa-2a
    • Drug: Ribavirin
    • Drug: GSK2336805 Matching Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
17
December 2011
December 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT01439373
115519
No
GlaxoSmithKline
GlaxoSmithKline
PPD
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP