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Trial registered on ANZCTR


Registration number
ACTRN12615001133527
Ethics application status
Approved
Date submitted
23/09/2015
Date registered
27/10/2015
Date last updated
30/01/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Open-Label, Single Dose Study to Evaluate the Safety and Efficacy of Nivolumab With or Without GS 4774 for the Treatment of Chronic Hepatitis B patients who are currently receiving oral antiviral treatment
Scientific title
A Phase 1, Open-Label, Single Dose Study to Evaluate the Safety and Efficacy of Nivolumab With or Without GS 4774 for the Treatment of Virally Suppressed Subjects with Chronic Hepatitis B
Secondary ID [1] 287528 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 296293 0
Condition category
Condition code
Infection 296570 296570 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately twenty four adult subjects with HBeAg-negative, Chronic Hepatitis B (CHB) and who are currently receiving treatment with an Oral Antiviral (OAV) will be assigned to one of the 4 dosing groups below:
The first four subjects will be assigned to:
Sentinel A: 2 subjects treated with single intravenous dose of nivolumab at 0.1 mg/kg on Day 1 of treatment and followed for 24 weeks after receiving nivolumab
Sentinel B: 2 subjects treated with single intravenous dose of nivolumab at 0.3 mg/kg on Day 1 of treatment and followed for 24 weeks after receiving nivolumab

Once safety is demonstrated in Sentinels A and B, a group of 10 subjects will be assigned to Cohort A and following completion of enrollment in this cohort, another group of 10 subjects will be assigned to Cohort B.
Cohort A: 10 subjects treated with single dose of intravenous nivolumab at up to 0.3 mg/kg on Day 1 of treatment and followed for 24 weeks after receiving nivolumab

Cohort B: 10 subjects treated with subcutaneous injection of GS 4774 40 YU on Day 1 of treatment and subcutaneous injection of GS 4774 40 YU plus single intravenous dose of nivolumab at up to 0.3 mg/kg on Day 28 and followed for 24 weeks after receiving nivolumab

Intervention code [1] 292922 0
Treatment: Drugs
Comparator / control treatment
Active comparator: Biological Vaccine GS-4774.
Depending on the treatment group you are assigned to, participants will receive subcutaneous injection of GS-4774 40 YU on Day 1 of treatment and Day 28
Control group
Active

Outcomes
Primary outcome [1] 296187 0
Mean change in serum HBsAg log10 IU/mL levels from Day 1 of nivolumab at Week 12 following nivolumab treatment. ?
The primary analysis set for efficacy analysis includes all subjects who have received at least 1 dose of study drug. This will be assessed in Sentinel A and B as well as Cohort A and B.
Timepoint [1] 296187 0
Serum HBsAg (quantitative) is collected at the following study visits by treatment arm:

1. Nivolumab only (Sentinel A, Sentinel B and Cohort A): Screening, Day 1 of treatment, Week 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, Early discontinuation
Sentinels A , B and Cohort A , subjects receive Nivolumab at Day 1 of treatment and are followed for 24 weeks ; thus completing the study in 24 weeks.

2. GS4774 plus Nivolumab (Cohort B): Screening, Day 1 of treatment, Week 2, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 28, Early discontinuation
Cohort B, subjects receive GS-4774 at Day 1 of treatment and then GS-4774 plus Nivolumab at Week 4 and subjects are followed for 24 weeks following the Nivolumab dosing; thus completing the study in 28 weeks.
Secondary outcome [1] 317746 0
Proportion of subjects with HBsAg loss and seroconversion at Week 24 following nivolumab treatment. This will be assessed in all treatment arms (Sentinel A and B, Cohort A and B)

Timepoint [1] 317746 0
Serum HBsAg (qualitative) is collected at the following study visits by treatment arm:

1. Nivolumab only (Sentinel A, Sentinel B and Cohort A): Screening, Day 1 of treatment, Week 12, 24, Early discontinuation
Sentinels A , B and Cohort A , subjects receive Nivolumab at Day 1 of treatment and are followed for 24 weeks ; thus completing the study in 24 weeks.

2. GS4774 plus Nivolumab (Cohort B): Screening, Day 1 of treatment, Week 16, 28, Early discontinuation
Cohort B, subjects receive GS-4774 at Day 1 of treatment and then GS-4774 plus Nivolumab at Week 4 and subjects are followed for 24 weeks following the Nivolumab dosing; thus completing the study in 28 weeks.

Secondary outcome [2] 317747 0
Mean change in serum HBsAg log10 IU/mL from Day 1 of nivolumab treatment at Week 4 following nivolumab treatment. This will be assessed in all treatment arms (Sentinel A and B, Cohort A and B)
Timepoint [2] 317747 0
Serum HBsAg (quantitative) is collected at the following study visits by treatment arm:

1. Nivolumab only (Sentinel A, Sentinel B and Cohort A): Screening, Day 1 of treatment, Week 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, Early discontinuation
Sentinels A , B and Cohort A , subjects receive Nivolumab at Day 1 of treatment and are followed for 24 weeks ; thus completing the study in 24 weeks.


2. GS4774 plus Nivolumab (Cohort B): Screening, Day 1 of treatment, Week 2, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 28, Early discontinuation
Cohort B, subjects receive GS-4774 at Day 1 of treatment and then GS-4774 plus Nivolumab at Week 4 and subjects are followed for 24 weeks following the Nivolumab dosing; thus completing the study in 28 weeks.
Secondary outcome [3] 317748 0
Proportion of subjects with a greter than/equal to 0.5 log10 IU/mL decline in serum HBsAg titers from Day 1 of nivolumab treatment at Weeks 4 and 12 following nivolumab treatment. This will be assessed in all treatment arms (Sentinel A and B, Cohort A and B)
Timepoint [3] 317748 0
Serum HBsAg (quantitative) is collected at the following study visits by treatment arm:

1. Nivolumab only (Sentinel A, Sentinel B and Cohort A): Screening, Day 1 of treatment, Week 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, Early discontinuation
Sentinels A , B and Cohort A , subjects receive Nivolumab at Day 1 of treatment and are followed for 24 weeks ; thus completing the study in 24 weeks.

2. GS4774 plus Nivolumab (Cohort B): Screening, Day 1 of treatment, Week 2, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, 28, Early discontinuation
Cohort B, subjects receive GS-4774 at Day 1 of treatment and then GS-4774 plus Nivolumab at Week 4 and subjects are followed for 24 weeks following the Nivolumab dosing; thus completing the study in 28 weeks.

Eligibility
Key inclusion criteria
1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study
2. Documented evidence of chronic HBV infection (e.g., HBsAg positive for more than 6 months)
3. Must be HBeAg negative at screening
4. Have been receiving approved HBV oral antiviral treatment for greater than/equal to 1 year prior to screening
5. A negative serum pregnancy test is required for female subjects (unless surgically sterile or greater than two years post-menopausal)
6. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cirrhosis
2. Inadequate liver function
3. Co-infection with hepatitis C virus (HCV), HIV or hepatitis D virus (HDV)
4. Evidence of hepatocellular carcinoma (e.g., as evidenced by recent imaging)
5. Presence of active infections
6. Women who are pregnant or may wish to become pregnant during the course of the study
7. Received solid organ or bone marrow transplant
8. Received prolonged therapy with immunomodulators (e.g., corticosteroids) or biologics (e.g., monoclonal Ab,
interferon) within 3 months of screening
9. Use of investigational agents within 3 months of screening
10. Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance
11. History of significant autoimmune disease
12. Documented history of yeast allergy
13. Known hypersensitivity to study drugs, metabolites or formulation excipients
14. Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical
resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 7181 0
New Zealand
State/province [1] 7181 0
Auckland

Funding & Sponsors
Funding source category [1] 292097 0
Commercial sector/Industry
Name [1] 292097 0
Gilead Sciences, Inc.
Address [1] 292097 0
333 Lakeside Drive, Foster City, California 94404
Country [1] 292097 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences, Inc.
Address
333 Lakeside Drive, Foster City, California 94404
Country
United States of America
Secondary sponsor category [1] 290776 0
None
Name [1] 290776 0
Address [1] 290776 0
Country [1] 290776 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293584 0
Health and Disability Ethics Committee (HDEC), NZ
Ethics committee address [1] 293584 0
Ethics committee country [1] 293584 0
New Zealand
Date submitted for ethics approval [1] 293584 0
01/10/2015
Approval date [1] 293584 0
27/11/2015
Ethics approval number [1] 293584 0
15/NTA/161/AM01

Summary
Brief summary
This study is to evaluate the safety, tolerability, and efficacy of nivolumab treatment with or without GS-4774 in adults with HBeAg-negative chronic hepatitis B infection and currently on oral antivirals treatment.
As per the treatment group, participants will be assigned to receive a single intravenous dose of nivolumab or a combination of dose of nivolumab and subcutaneous injections of GS-4774. All subjects will be followed for 24 weeks after receiving nivolumab
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60554 0
Prof Edward Gane
Address 60554 0
Auckland Clinical Studies Limited
3 Ferncroft St., Auckland 1042
Country 60554 0
New Zealand
Phone 60554 0
+64 9 373 3474
Fax 60554 0
Email 60554 0
edgane@adhb.govt.nz
Contact person for public queries
Name 60555 0
Ms Ansy Mathews
Address 60555 0
333 Lakeside Drive, Gilead Sciences, Inc.
Foster City, California 94404
Country 60555 0
United States of America
Phone 60555 0
+1 6505243912
Fax 60555 0
Email 60555 0
Ansy.mathews@gilead.com
Contact person for scientific queries
Name 60556 0
Ms Ansy Mathews
Address 60556 0
Gilead Sciences, Inc.
333 Lakeside Drive, Foster City, California 94404
Country 60556 0
United States of America
Phone 60556 0
+1 6505243912
Fax 60556 0
Email 60556 0
Ansy.mathews@gilead.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary