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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02174276




Registration number
NCT02174276
Ethics application status
Date submitted
23/06/2014
Date registered
25/06/2014
Date last updated
4/06/2019

Titles & IDs
Public title
Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Participants With Chronic Hepatitis B (CHB) and Who Are Currently Not on Treatment
Scientific title
A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment
Secondary ID [1] 0 0
2014-001011-39
Secondary ID [2] 0 0
GS-US-330-1401
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tenofovir disoproxil fumarate
Other interventions - GS-4774

Active Comparator: TDF 48 weeks - Participants will receive TDF for 48 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.

Experimental: TDF plus GS-4774 2 YU - Participants will receive TDF plus GS-4774 2 yeast units (YU) for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.

Experimental: TDF plus GS-4774 10 YU - Participants will receive TDF plus GS-4774 10 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.

Experimental: TDF plus GS-4774 40 YU - Participants will receive TDF plus GS-4774 40 YU for 20 weeks. After Week 20, GS-4774 will be discontinued and participants will continue on TDF for an additional 28 weeks. After Week 48, participants will have the option to continue receiving TDF for up to 144 weeks.


Treatment: Drugs: Tenofovir disoproxil fumarate
TDF 300 mg tablet administered orally once daily

Other interventions: GS-4774
GS-4774 subcutaneous injection administered every 4 weeks for a total of 6 doses

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change in Serum HBsAg From Baseline to Week 24 - The change from baseline to Week 24 in HBsAg was analyzed using a mixed effect model for repeated measures (MMRM). The model included treatment groups, ALT levels (> ULN or = ULN) at baseline, HBeAg status (positive or negative) at baseline, HBsAg level at baseline, visit and treatment-by-visit interaction as fixed effects and visit as a repeated measurement. Estimated least square means of treatment effects are presented with the 95% confidence intervals (CIs).
Timepoint [1] 0 0
Baseline to Week 24
Secondary outcome [1] 0 0
Mean Change in HBsAg From Baseline to Week 12 - The change from baseline to Week 12 in HBsAg was analyzed using a MMRM. The model included treatment groups, ALT levels (> ULN or = ULN) at baseline, HBeAg status (positive or negative) at baseline, HBsAg level at baseline, visit and treatment-by-visit interaction as fixed effects and visit as a repeated measurement. Estimated least square means of treatment effects are presented with the 95% CIs.
Timepoint [1] 0 0
Baseline to Week 12
Secondary outcome [2] 0 0
Mean Change in HBsAg From Baseline to Week 48 - The change from baseline to Week 48 in HBsAg was analyzed using a MMRM. The model included treatment groups, ALT levels (> ULN or = ULN) at baseline, HBeAg status (positive or negative) at baseline, HBsAg level at baseline, visit and treatment-by-visit interaction as fixed effects and visit as a repeated measurement. Estimated least square means of treatment effects are presented with the 95% CIs.
Timepoint [2] 0 0
Baseline to Week 48
Secondary outcome [3] 0 0
Percentage of Participants With HBsAg Loss at Week 24 - HBsAg loss was defined as qualitative HBsAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window.
Timepoint [3] 0 0
Baseline to Week 24
Secondary outcome [4] 0 0
Percentage of Participants With HBsAg Loss at Week 48 - HBsAg loss was defined as qualitative HBsAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window.
Timepoint [4] 0 0
Baseline to Week 48
Secondary outcome [5] 0 0
Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24 - HBsAg loss was defined as qualitative HBsAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg loss and seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit and the participant must have achieved HBsAg loss within the targeted time window.
Timepoint [5] 0 0
Baseline to Week 24
Secondary outcome [6] 0 0
Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48 - HBsAg loss was defined as qualitative HBsAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg loss and seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit and the participant must have achieved HBsAg loss within the targeted time window.
Timepoint [6] 0 0
Baseline to Week 48
Secondary outcome [7] 0 0
Percentage of Participants With a = 0.5 Log10 IU/mL or a = 1.0 Log10 IU/mL Decline in HBsAg at Week 12 - HBsAg with a = 0.5 or = 1.0 log10 IU/mL decline was defined as = 0.5 or = 1.0 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.
Timepoint [7] 0 0
Baseline to Week 12
Secondary outcome [8] 0 0
Percentage of Participants With a = 0.5 Log10 IU/mL or a = 1.0 Log10 IU/mL Decline in HBsAg at Week 24 - HBsAg with a = 0.5 or = 1.0 log10 IU/mL decline was defined as = 0.5 or = 1.0 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.
Timepoint [8] 0 0
Baseline to Week 24
Secondary outcome [9] 0 0
Percentage of Participants With a = 0.5 Log10 IU/mL or a = 1.0 Log10 IU/mL Decline in HBsAg at Week 48 - HBsAg with a = 0.5 or = 1.0 log10 IU/mL decline was defined as = 0.5 or = 1.0 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window.
Timepoint [9] 0 0
Baseline to Week 48
Secondary outcome [10] 0 0
Percentage of Participants With HBeAg Loss at Week 24 - HBeAg loss was defined as qualitative HBeAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window.
Timepoint [10] 0 0
Baseline to Week 24
Secondary outcome [11] 0 0
Percentage of Participants With HBeAg Loss at Week 48 - HBeAg loss was defined as qualitative HBeAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window.
Timepoint [11] 0 0
Baseline to Week 48
Secondary outcome [12] 0 0
Composite Endpoint Measuring the Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 24 - HBeAg loss was defined as qualitative HBeAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBeAg loss and seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit and the participant must have achieved HBeAg loss within the targeted time window.
Timepoint [12] 0 0
Baseline to Week 24
Secondary outcome [13] 0 0
Composite Endpoint Measuring the Percentage of Participants With HBeAg Loss and HBeAg Seroconversion at Week 48 - HBeAg loss was defined as qualitative HBeAg test changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBeAg loss and seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit and the participant must have achieved HBeAg loss within the targeted time window.
Timepoint [13] 0 0
Baseline to Week 48
Secondary outcome [14] 0 0
Percentage of Participants With HBV DNA < Lower Limit of Quantification (LLOQ) at Week 24 - The LLOQ was defined as 20 IU/mL.
Timepoint [14] 0 0
Week 24
Secondary outcome [15] 0 0
Percentage of Participants With HBV DNA < LLOQ at Week 48 - The LLOQ was defined as 20 IU/mL.
Timepoint [15] 0 0
Week 48
Secondary outcome [16] 0 0
Percentage of Participants Experiencing Virologic Breakthrough at Week 24 - Virologic breakthrough was defined as HBV DNA = 69 IU/mL after having been < 69 IU/mL, or having had = 1.0 log10 increase in HBV DNA from nadir. Two consecutive visits that met the definition were required for a participant to be classified as having had virologic breakthrough.
Timepoint [16] 0 0
Baseline to Week 24
Secondary outcome [17] 0 0
Percentage of Participants Experiencing Virologic Breakthrough at Week 48 - Virologic breakthrough was defined as HBV DNA = 69 IU/mL after having been < 69 IU/mL, or a = 1.0 log10 increase in HBV DNA from nadir. Two consecutive visits that met the definition were required for a participant to be classified as having had virologic breakthrough.
Timepoint [17] 0 0
Baseline to Week 48
Secondary outcome [18] 0 0
Number of Participants With Drug-Resistance Mutations at Week 48 or at the Last Visit Available - Resistance surveillance analysis was conducted at Week 48 or Early Discontinuation (with at least 24 weeks of exposure to TDF) for any participants who met inclusion criteria (HBV DNA = 69 IU/mL). Drug-resistant mutation status was assessed using HBV polymerase/ reverse transcriptase (pol/RT) population sequencing.
Timepoint [18] 0 0
Baseline to Week 48

Eligibility
Key inclusion criteria
Key

- Must have the ability to understand and sign a written informed consent form, which
must be obtained prior to initiation of study

- Documented evidence of chronic hepatitis B virus (HBV) infection, for example,
hepatitis B surface antigen (HBsAg) positive for more than 6 months

- Screening HBV DNA = 2000 IU/mL

- A negative serum pregnancy test is required for females (unless surgically sterile or
> 2 years post-menopausal)

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Cirrhosis

- Inadequate liver function

- Co-infection with hepatitis C virus (HCV), HIV or hepatitis D virus (HDV)

- Received antiviral treatment for HBV within 3 months of screening

- Evidence of hepatocellular carcinoma (eg, as evidenced by recent imaging)

- Significant cardiovascular, pulmonary, or neurological disease

- Women who are pregnant or may wish to become pregnant during the course of the study

- Received solid organ or bone marrow transplant

- Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics
(eg, monoclonal antibody, interferon) within 3 months of screening

- Use of investigational agents within 3 months of screening

- Current alcohol or substance abuse judged by the investigator to potentially interfere
with individual's compliance

- Receipt of immunoglobulin or other blood products within 3 months prior to enrollment

- History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease,
Ulcerative colitis, or autoimmune disease

- Documented history of yeast allergy

- Known hypersensitivity to study drugs, metabolites or formulation excipients

- Malignancy within 5 years prior to screening, with the exception of specific cancers
that are cured by surgical resection (basal cell skin cancer, etc). Individuals under
evaluation for possible malignancy are not eligible

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Hawaii
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
Canada
State/province [8] 0 0
British Columbia
Country [9] 0 0
Canada
State/province [9] 0 0
Manitoba
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Italy
State/province [11] 0 0
Bologna
Country [12] 0 0
Italy
State/province [12] 0 0
Parma
Country [13] 0 0
Italy
State/province [13] 0 0
Pisa
Country [14] 0 0
Italy
State/province [14] 0 0
San Giovanni Rotondo
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Daegu
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seocho
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seongnam
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Yangsan
Country [20] 0 0
New Zealand
State/province [20] 0 0
Auckland
Country [21] 0 0
Romania
State/province [21] 0 0
Bucharest

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are to evaluate the safety, tolerability, and efficacy
of GS-4774 in adults with CHB and who are currently not on treatment. Participants will be
randomized to receive TDF alone or GS-4774 plus TDF for 20 weeks. After Week 20, GS-4774 will
be discontinued. All participants will continue on TDF and will be followed for an additional
28 weeks. Following completion of the 48 week study period, all participants will be eligible
for a treatment extension for 96 weeks.
Trial website
https://clinicaltrials.gov/show/NCT02174276
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications