ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Chronic Hepatitis B

Condition category

Condition code

Infection

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]

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]

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]

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]

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]

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]

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]

Secondary outcome [3]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

23/11/2015

Actual

14/12/2015

Date of last participant enrolment

Anticipated

Actual

16/05/2016

Date of last data collection

Anticipated

Actual

28/11/2016

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Gilead Sciences, Inc.

Address [1]

333 Lakeside Drive, Foster City, California 94404

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Health and Disability Ethics Committee (HDEC), NZ

Ethics committee address [1]

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

01/10/2015

Approval date [1]

27/11/2015

Ethics approval number [1]

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

Prof Edward Gane

Address

Auckland Clinical Studies Limited
3 Ferncroft St., Auckland 1042

Country

New Zealand

Phone

+64 9 373 3474

Fax

[email protected]

Contact person for public queries

Name

Ansy Mathews

Address

333 Lakeside Drive, Gilead Sciences, Inc.
Foster City, California 94404

Country

United States of America

Phone

+1 6505243912

Fax

[email protected]

Contact person for scientific queries

Name

Ansy Mathews

Address

Gilead Sciences, Inc.
333 Lakeside Drive, Foster City, California 94404

Country

United States of America

Phone

+1 6505243912

Fax

[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

Source	Title	Year of Publication	DOI
Dimensions AI	Defective T-cell immunity in hepatitis B virus infection: why therapeutic vaccination needs a helping hand	2018	https://doi.org/10.1016/s2468-1253(18)30007-4
Embase	Anti-PD-1 blockade with nivolumab with and without therapeutic vaccination for virally suppressed chronic hepatitis B: A pilot study.	2019	https://dx.doi.org/10.1016/j.jhep.2019.06.028
Embase	Is PD-1 blockade a potential therapy for HBV?.	2019	https://dx.doi.org/10.1016/j.jhepr.2019.07.007
Embase	Advances in Targeting the Innate and Adaptive Immune Systems to Cure Chronic Hepatitis B Virus Infection.	2020	https://dx.doi.org/10.3389/fimmu.2019.03127
Dimensions AI	Toward a new era of hepatitis B virus therapeutics: The pursuit of a functional cure	2021	https://doi.org/10.3748/wjg.v27.i21.2727
Embase	New strategies for the treatment of chronic hepatitis B.	2022	https://dx.doi.org/10.1016/j.molmed.2022.06.002

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically