Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613001080718
Ethics application status
Approved
Date submitted
18/09/2013
Date registered
26/09/2013
Date last updated
26/09/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 2, Randomized, Open-Label Study to Evaluate the
Safety and Efficacy of GS-4774 for the Treatment of
Virally-Suppressed Subjects with Chronic Hepatitis B
Scientific title
A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 for the Treatment of Virally-Suppressed Subjects with Chronic Hepatitis B
Secondary ID [1] 283302 0
Nil
Universal Trial Number (UTN)
U1111-1147-8339
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Virally-Suppressed Subjects with Chronic Hepatitis B 289878 0
Condition category
Condition code
Infection 290241 290241 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment Arm A: 25 subjects continue Oral Antiviral alone
Treatment Arm B: 50 subjects OAV + GS-4774 2 YU (Yeast Units)subcutaneous injection every four weeks for 6 doses
Treatment Arm C: 50 subjects OAV + GS-4774 10 YU
subcutaneous injection every four weeks for 6 doses
Treatment Arm D: 50 subjects OAV + GS-4774 40 YU
subcutaneous injection every four weeks for 6 doses
a) the dose of GS-4774 administered is GS 4774 2YU (Yeast Units) or 10YU or 40YU or Oral antiviral alone
b) Administered every 4 weeks for 6 doses
c) Mode of administration, Oral antirvial and GS 4774 subcutaneous injection
d) We will be collecting patient reported adherence to OAV at each study visit on the Electronic Data Base.
Intervention code [1] 287763 0
Treatment: Drugs
Comparator / control treatment
Treatment Arm A is the control Group
Control group
Active

Outcomes
Primary outcome [1] 290262 0
To evaluate the safety and tolerability of GS-4774 in subjects
with chronic hepatitis B infection (CHB)
We will assess safety parameters including adverse events, laboratory changes, serious adverse events as well as discontinuations of study drug due to AEs to help determine the safety and tolerability of the GS-4774 treatments.
Injection site reactions comprised the majority of adverse events seen in the Phase 1 study of GS-4774 in healthy volunteers. These reactions included pain, warmth, erythema, swelling or induration over the injection site. Over 99% of these injection site reactions were mild and all resolved with only two requiring treatment (one requiring ice, the other paracetamol). Headache, seen in 27% of subjects, was the only other adverse event seen in >10% of subjects.
Timepoint [1] 290262 0
We are collecting safety data for the entirety of the study that we will reviewat safety and tolerability until Week 48 in the first instance
Primary outcome [2] 290591 0
To evaluate the efficacy of GS-4774 at week 24 as measured by
the change from Baseline in serum Hepatitis B surface Antigen
(HBsAg) (log10 IU/mL) titers
Timepoint [2] 290591 0
Week 24
Secondary outcome [1] 304221 0
1.To evaluate the rates of HBsAg loss and seroconversion at Weeks 24 and 48
Evaluated with serum tests of presence of HBsAg and HBsAb
Timepoint [1] 304221 0
1. Weeks 24 and 48
Secondary outcome [2] 304857 0
2. To evaluate the rates of HBeAg loss and seroconversion at Weeks 24 and 48
Evaluated with serum tests of presence of HBeAg and HBeAb
Timepoint [2] 304857 0
Weeks 24 and 48
Secondary outcome [3] 304858 0
3.To evaluate the change in log10 IU/mL serum HBsAg from Baseline to Weeks 12 and 48
Evaluated with serum tests of quantitative HBsAg levels (Abbott Architect Assay)
Timepoint [3] 304858 0
Baseline to Weeks 12 and 48
Secondary outcome [4] 304859 0
4.To evaluate the proportion of subjects with a 1-log decline in HBsAg at Weeks 12, 24 and 48
Evaluated with serum tests of quantitative HBsAg levels (Abbott Architect Assay)
Timepoint [4] 304859 0
Weeks 12, 24 and
48

Eligibility
Key inclusion criteria
1. Documented evidence of chronic HBV infection (e.g., HBsAg positive for more than
6 months)
2. Virally-suppressed (screening HBV DNA <29 IU/mL) with HBV DNA below the lower
limit of quantification
3. Ability to understand and sign a writtent informed consent form, which must be obtained prior to initiation of study procedures
4. Currently taking an HBV oral antiviral medication
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cirrhosis
2. Co-infection with HCV, HIV or HDV
3. Evidence of hepatocellular carcinoma (e.g., as evidenced by recent imaging)
4. Significant cardiovascular, pulmonary, or neurological disease
5. Received solid organ or bone marrow transplant
6. Received prolonged therapy with immunomodulators (e.g., corticosteroids) or biologics
(e.g., monoclonal Ab, interferon) within 3 months of screening
7. Use of another investigational agents within 3 months of screening
8. Current alcohol or substance abuse judged by the investigator to potentially interfere with
subject compliance
9. Receipt of immunoglobulin or other blood products within 3 months of screening
10. Known hypersensitivity to study drug, metabolites or formulation excipients

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)
It is the responsibility of the investigator to ensure that subjects are eligible to participate in
the study prior to enrollment. Each study candidate must sign an Informed Consent Form
prior to the conduct of any screening procedures, in accordance with regulatory and local
Ethics Committee requirements. Once consent has been obtained, all screening tests and
procedures have been completed, and study eligibility has been confirmed, subjects will be
randomized using an Interactive Voice Randomisation System (IVRS) or Interactive Web Randomisation System (IWRS).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomization will be performed via an Interactive Voice Response System (IVRS) or
Interactive Web Response System (IWRS)
Randomization list was generated by the IWRS vendor (Bracket).
The vendor’s statistician prepared a randomization program in SAS. A dummy list was also generated using a random seed. A Gilead’s statistician reviewed the program and the output for accuracy. The vendor’s statistician then generated the final list using a different seed than the seed used in the dummy list. This is a stratified randomization using a randomization table created by computer software (SAS). Treatments were randomly assigned . Two stratification factors were employed: HBeAg status (Positive vs Negative) and HBsAg level (> 1000 IU/mL vs <= 1000 IU/mL).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Nil
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary analysis will be performed when the last subject
reaches Week 24. The analysis will compare the OAV only arm to
the OAV + 2 YU GS-4774 arm, the OAV + 10 YU GS-4774 arm
and the OAV + 40YU GS-4774 arm, respectively.
With respect to the primary efficacy endpoint, the change from Baseline to Week 24 in HBsAg (log10Iu/ml), a sample size of 25 in the OAV only arm and 50 in an OAV=GS-4774 arm will have at least 80% power to detect a difference of 0.15 log 10 HBsAg (IU/ml) between the OAV only arm and each of the OAV+GS-4774 arm. This sample size calculation assumes a change from Baseline to week 24 in the OAV only arm of -0.12 log 10IU/ml, with a common standard deviation of 0.179 log10 IU/ml, and an alpha level of 0.016 (adjusting for 3 test arms). These assumptions were derived from studies GS-US-174-0102 and GS-US-174-0103.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
13/09/2013
Actual
Date of last participant enrolment
Anticipated
1/04/2014
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
175
Accrual to date
Final
Recruitment outside Australia
Country [1] 5320 0
United States of America
State/province [1] 5320 0
Country [2] 5321 0
Canada
State/province [2] 5321 0
Country [3] 5411 0
Korea, Republic Of
State/province [3] 5411 0
Country [4] 5415 0
New Zealand
State/province [4] 5415 0

Funding & Sponsors
Funding source category [1] 287809 0
Commercial sector/Industry
Name [1] 287809 0
Gilead Sciences, Inc
Country [1] 287809 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences, Inc
Address
333 Lakeside Drive
Foster City, CA 94404
Country
United States of America
Secondary sponsor category [1] 286536 0
Commercial sector/Industry
Name [1] 286536 0
PRA: Pharmaceutical Research Associates
Address [1] 286536 0
Suite 1701, Central Square, 323 Castlereagh St
Sydney N.S.W. Australia 2000
Country [1] 286536 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289759 0
Chesapeake Research Review, Inc.
Ethics committee address [1] 289759 0
7063 Columbia Gateway Drive, Suite 110
Columbia, MD 21046
Ethics committee country [1] 289759 0
United States of America
Date submitted for ethics approval [1] 289759 0
20/08/2013
Approval date [1] 289759 0
29/08/2013
Ethics approval number [1] 289759 0

Summary
Brief summary
GS-4774 is an experimental (investigational) vaccine being tested as a possible treatment of chronic Hepatitis B and is not yet approved by the United States Food and Drug Administration (FDA). GS-4774 has been designed to stimulate your immune system, the system that your body uses to defend itself from infections. GS-4774 is produced from “baker’s yeast” which has been changed to include the substance found in the Hepatitis B virus. This yeast has been heat inactivated and you will not be receiving live yeast. Studies in healthy subjects have shown that GS-4774 stimulated the immune system to help block the spread of Hepatitis B virus.

The purpose of this study is to determine how well your body tolerates GS-4774 and how it affects the HBV infection in your body in addition to the oral antiviral treatment regimen you are currently receiving. The study is for research purposes only and is not intended or expected to cure any medical conditions. As this is a research study, GS-4774 will only be given to you during your participation of the trial.
Trial website
Not applicable
Trial related presentations / publications
Not applicable
Public notes
Not applicable

Contacts
Principal investigator
Name 42266 0
Prof Edward Gane
Address 42266 0
Auckland Clinical Studies
3 Ferncroft Street
Ground Floor ECOM Building
Grafton
AUCKLAND 1142
Country 42266 0
New Zealand
Phone 42266 0
+64 9307 4949
Fax 42266 0
+64 9 373 3479
Email 42266 0
[email protected]
Contact person for public queries
Name 42267 0
Ms Allison Fidelholtz
Address 42267 0
Clinical Program Manager, Clinical Operations
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Country 42267 0
United States of America
Phone 42267 0
+1 650-577-6585
Fax 42267 0
+1 650-524-9418
Email 42267 0
[email protected]
Contact person for scientific queries
Name 42268 0
Dr Anuj Gaggar, MD, PhD
Address 42268 0
Associate Director, Clinical Research, Medical Monitor
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Country 42268 0
United States of America
Phone 42268 0
+1 650-358-1090
Fax 42268 0
+1 650-524-9272
Email 42268 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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