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A Phase 1b Study Assessing GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01671787
First received: August 21, 2012
Last updated: May 7, 2013
Last verified: May 2013
History of Changes
  Purpose

This is an open-label study evaluating multiple doses of GS-7340 versus Tenofovir disoproxil fumarate (TDF).


Condition Intervention Phase
Chronic Hepatitis B
 Drug: GS-7340
Drug: Tenofovir disoproxil fumarate
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Randomized, Open Label, Active-Controlled Study to Assess the Safety, Viral Kinetics, and Anti-HBV Activity of GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B (CHB) Infection

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change in serum HBV DNA [ Time Frame: Up to Week 4 ] [ Designated as safety issue: No ]
    Time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for GS-7340 8-, 25-, 40 and 120-mg.


Secondary Outcome Measures:
  • Change in HBV DNA for tenofovir disoproxil fumarate (TDF) [ Time Frame: Up to Week 4 ] [ Designated as safety issue: No ]
    Comparing the short-term antiviral activity of GS-7340 with TDF 300mg. This is measured by time-weighted average change from baseline through Week 4 (DAVG4) in serum HBV DNA (log10 IU/mL) for TDF.

  • Change in HBV DNA of GS-7340 through 28 days of therapy [ Time Frame: Up to week 4 ] [ Designated as safety issue: No ]
    Time weighted change from baseline to day 29 (DAVG4) in serum HBV DNA (log10 IU/mL)

  • Pharmacokinetics (PK) of GS-7340 and/or tenofovir (TVF) following single and multiple doses of GS-7340 and TDF [ Time Frame: Up to week 4 ] [ Designated as safety issue: No ]

    GS-7340 and tenofovir (TFV) PK parameters in plasma will be calculated as applicable: Cmax, Tmax, Clast, Tlast, T1/2, λz, AUC0-t, AUC0-last, AUC0-∞, %AUCexp.

    PK samples are collected on:

    • Baseline/Day 1: 0 (predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post dose
    • Additional predose plasma samples will be collected on Days 2, 5, 8, 10, 15, 19, 22, and 29/ET.

  • Safety and Tolerability of Therapy [ Time Frame: Up to week 4 ] [ Designated as safety issue: Yes ]
    Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities


Estimated Enrollment: 50
Study Start Date: March 2012
Estimated Study Completion Date: May 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GS-7340 8mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
 Drug: GS-7340
Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.
Other Name: GS-7340
Experimental: GS-7340 25mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
 Drug: GS-7340
Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.
Other Name: GS-7340
Experimental: GS-7340 40mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
 Drug: GS-7340
Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.
Other Name: GS-7340
Experimental: GS-7340 120mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
 Drug: GS-7340
Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.
Other Name: GS-7340
Experimental: Tenofovir disoproxil fumarate 300mg
After Screening procedures, eligible subjects will be randomized 1:1:1:1:1 to receive either open-label GS-7340 8, 25, 40, or 120 mg (3 x 40 mg), or open-label TDF 300 mg for 28 days.
 Drug: Tenofovir disoproxil fumarate
Subjects will receive 300mg of Tenofovir disoproxil fumarate (TDF) over 28 days of therapy
Other Name: Viread

Detailed Description:

This is a randomized, open-label, active-controlled study whose primary objective is to evaluate the safety and efficacy of several doses of GS-7340. This study will evaluate the safety, viral kinetics, and antiviral activity of 4 different doses of GS-7340 over 28 days of therapy. In addition, the study will evaluate the antiviral activity of an optimal dose of GS-7340 versus 300mg Tenofovir disoproxil fumarate (TDF) over 28 days of therapy.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be between 18 and 65 years of age
  • Must have Screening plasma HBV DNA ≥ 2x10^3 IU/mL
  • Must have chronic HBV infection for at least 6 months
  • Must have estimated creatinine clearance (CLCr) ≥ 70 mL/min
  • Not pregnant or nursing
  • Women must be of non-childbearing potential OR of childbearing potential with confirmed negative pregnancy tests
  • Consistent and correct use of recommended methods of birth control for men and women

Exclusion Criteria:

  • Pregnant or lactating subjects
  • Receipt of anti-HBV nucleoside/nucleotide therapy. Subjects who have failed prior Interferon treatment, greater than 6 months prior to screening, are permitted to participate in the study screening
  • Known co-infection with HIV, HCV or HDV
  • Presence of autoimmune disorders
  • History of liver disease other than Hepatitis B
  • History of Gilbert's Disease
  • Any sign of decompensated liver disease
  • Known or suspected cirrhosis
  • Evidence of hepatocellular carcinoma
  • Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
  • Electrolyte abnormalities
  • History of treatment that permanently alters the gastric condition
  • Alcohol or substance abuse
  • History of bleeding diathesis
  • Significant bone disease
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01671787

Locations
United States, California
Research and Education Inc.
San Diego, California, United States, 92105
United States, Maryland
University of Maryland Institute of Human Virology
Baltimore, Maryland, United States, 21201
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Texas
Baylor College of Medicine - St. Luke's Episcopal Hospital
Houston, Texas, United States, 77030
Australia, Victoria
Monash Medical Centre
Melborne, Victoria, Australia, 03168
Austin Health
Melbourne, Victoria, Australia, 3084
Alfred Hospital
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
Linear Clinical Research Ltd
Nedlands, Western Australia, Australia, 6009
Canada, British Columbia
Downtown Infectious Diseases Clinic (University of British Columbia)
Vancouver, British Columbia, Canada, V6Z2C9
Canada, Ontario
The Ottawa Hospital, General Campus
Ottawa, Ontario, Canada, K1H8L6
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Canada, Quebec
Algorithme Pharma
Montreal, Quebec, Canada, H3P3P1
Pro-recherche
St. Romuald, Quebec, Canada, G6W 8H1
New Zealand
Auckland Clinical Studies
Auckland, New Zealand, 1042
United Kingdom
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom, B152TH
Institute of Liver Studies, King's College Hospital
London, United Kingdom, SE5 9RS
University College London Hospital
London, United Kingdom, NW1-2BU
Grahame Hayton Unit
London, United Kingdom, E1 1BB
Nottingham University Hospitals NHS Trust - Queens Medical Centre
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John Flaherty, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01671787     History of Changes
Other Study ID Numbers: GS-US-320-0101
Study First Received: August 21, 2012
Last Updated: May 7, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Australia: National Health and Medical Research Council
United Kingdom: Medicines and Healthcare Products Regulatory Agency
New Zealand: Ministry of Health

Keywords provided by Gilead Sciences:
Hepatitis B
HBV
GS-7340
TDF
 Tenofovir disoproxil fumarate
Gilead
Viread

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
 DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 21, 2013