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

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GS-7340
Tenofovir disoproxil fumarate
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Hepatitis B, HBV, GS-7340, TDF, Tenofovir disoproxil fumarate, Gilead, Viread

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, hepatitis C virus (HCV) or hepatitis D virus (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

Sites / Locations

  • Research and Education Inc.
  • University of Maryland Institute of Human Virology
  • Henry Ford Health System
  • Baylor College of Medicine - St. Luke's Episcopal Hospital
  • Monash Medical Centre
  • Alfred Hospital
  • Austin Health
  • Linear Clinical Research Ltd
  • Downtown Infectious Diseases Clinic (University of British Columbia)
  • The Ottawa Hospital, General Campus
  • Toronto General Hospital
  • Algorithme Pharma
  • Pro-recherche
  • Auckland Clinical Studies
  • University Hospitals Birmingham NHS Foundation Trust
  • Grahame Hayton Unit
  • University College London Hospital
  • Institute of Liver Studies, King's College Hospital
  • Nottingham University Hospitals NHS Trust - Queens Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

GS-7340 8mg

GS-7340 25mg

GS-7340 40mg

GS-7340 120mg

Tenofovir disoproxil fumarate 300mg

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Change in serum hepatitis B virus (HBV) DNA
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)
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 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
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/End of Treatment.
Safety and Tolerability of Therapy
Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities

Full Information

First Posted
August 21, 2012
Last Updated
October 19, 2018
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01671787
Brief Title
A Phase 1b Study Assessing GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Hepatitis B, HBV, GS-7340, TDF, Tenofovir disoproxil fumarate, Gilead, Viread

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GS-7340 8mg
Arm Type
Experimental
Arm Description
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.
Arm Title
GS-7340 25mg
Arm Type
Experimental
Arm Description
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.
Arm Title
GS-7340 40mg
Arm Type
Experimental
Arm Description
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.
Arm Title
GS-7340 120mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Tenofovir disoproxil fumarate 300mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GS-7340
Intervention Description
Subjects are randomized to receive one of four different doses of GS-7340 over 28 days of therapy.
Intervention Type
Drug
Intervention Name(s)
Tenofovir disoproxil fumarate
Other Intervention Name(s)
Viread
Intervention Description
Subjects will receive 300mg of Tenofovir disoproxil fumarate (TDF) over 28 days of therapy
Primary Outcome Measure Information:
Title
Change in serum hepatitis B virus (HBV) DNA
Description
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.
Time Frame
Up to Week 4
Secondary Outcome Measure Information:
Title
Change in HBV DNA for tenofovir disoproxil fumarate (TDF)
Description
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.
Time Frame
Up to Week 4
Title
Change in HBV DNA of GS-7340 through 28 days of therapy
Description
Time weighted change from baseline to day 29 (DAVG4) in serum HBV DNA (log10 IU/mL)
Time Frame
Up to week 4
Title
Pharmacokinetics (PK) of GS-7340 and/or tenofovir (TVF) following single and multiple doses of GS-7340 and TDF
Description
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/End of Treatment.
Time Frame
Up to week 4
Title
Safety and Tolerability of Therapy
Description
Safety and tolerability is measured by the incidence of adverse events and graded laboratory abnormalities
Time Frame
Up to week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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, hepatitis C virus (HCV) or hepatitis D virus (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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Flaherty, MD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Research and Education Inc.
City
San Diego
State/Province
California
ZIP/Postal Code
92105
Country
United States
Facility Name
University of Maryland Institute of Human Virology
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Baylor College of Medicine - St. Luke's Episcopal Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Monash Medical Centre
City
Melborne
State/Province
Victoria
ZIP/Postal Code
03168
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Austin Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Linear Clinical Research Ltd
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Downtown Infectious Diseases Clinic (University of British Columbia)
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z2C9
Country
Canada
Facility Name
The Ottawa Hospital, General Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H8L6
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Algorithme Pharma
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3P3P1
Country
Canada
Facility Name
Pro-recherche
City
St. Romuald
State/Province
Quebec
ZIP/Postal Code
G6W 8H1
Country
Canada
Facility Name
Auckland Clinical Studies
City
Auckland
ZIP/Postal Code
1042
Country
New Zealand
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B152TH
Country
United Kingdom
Facility Name
Grahame Hayton Unit
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
University College London Hospital
City
London
ZIP/Postal Code
NW1-2BU
Country
United Kingdom
Facility Name
Institute of Liver Studies, King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust - Queens Medical Centre
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
http://www.gilead.com/research/disclosure-and-transparency

Learn more about this trial

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

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