Safety, Tolerability and Antiviral Activity of Selgantolimod in Virally-Suppressed Participants With Chronic Hepatitis B

NCT ID: NCT03491553

Last Updated: 2021-08-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-06

Study Completion Date

2020-08-10

Brief Summary

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The primary objectives of this study are to evaluate the safety, tolerability and antiviral activity of selgantolimod (formerly GS-9688) in virally suppressed chronic hepatitis B (CHB) adults on oral antiviral (OAV) agents.

Detailed Description

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Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Selgantolimod 3 mg: HBeAg-positive CHB Participants

Participants with Hepatitis B e Antigen (HBeAg)-positive CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/early discontinuation (ED). At Week 48, per Principal Investigator's (PI's) discretion, participants can continue in the Treatment Free Follow-Up (TFFU) phase for up to an additional 48 weeks.

Group Type EXPERIMENTAL

Selgantolimod

Intervention Type DRUG

Tablet(s) administered orally once weekly

Hepatitis B virus (HBV) OAV Therapy

Intervention Type DRUG

Commercially available HBV OAV therapy could include one of the following:

Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)

Selgantolimod 3 mg: HBeAg-negative CHB Participants

Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.

Group Type EXPERIMENTAL

Selgantolimod

Intervention Type DRUG

Tablet(s) administered orally once weekly

Hepatitis B virus (HBV) OAV Therapy

Intervention Type DRUG

Commercially available HBV OAV therapy could include one of the following:

Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)

Selgantolimod 1.5 mg: HBeAg-positive CHB Participants

Participants with HBeAg-positive CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.

Group Type EXPERIMENTAL

Selgantolimod

Intervention Type DRUG

Tablet(s) administered orally once weekly

Placebo

Intervention Type DRUG

Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly

Hepatitis B virus (HBV) OAV Therapy

Intervention Type DRUG

Commercially available HBV OAV therapy could include one of the following:

Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)

Selgantolimod 1.5 mg: HBeAg-negative CHB Participants

Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.

Group Type EXPERIMENTAL

Selgantolimod

Intervention Type DRUG

Tablet(s) administered orally once weekly

Placebo

Intervention Type DRUG

Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly

Hepatitis B virus (HBV) OAV Therapy

Intervention Type DRUG

Commercially available HBV OAV therapy could include one of the following:

Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)

Placebo: HBeAg-positive CHB Participants

Participants with HBeAg-positive CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly

Hepatitis B virus (HBV) OAV Therapy

Intervention Type DRUG

Commercially available HBV OAV therapy could include one of the following:

Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)

Placebo: HBeAg-negative CHB Participants

Participants with HBeAg-negative CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly

Hepatitis B virus (HBV) OAV Therapy

Intervention Type DRUG

Commercially available HBV OAV therapy could include one of the following:

Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)

Interventions

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Selgantolimod

Tablet(s) administered orally once weekly

Intervention Type DRUG

Placebo

Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly

Intervention Type DRUG

Hepatitis B virus (HBV) OAV Therapy

Commercially available HBV OAV therapy could include one of the following:

Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)

Intervention Type DRUG

Other Intervention Names

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GS-9688

Eligibility Criteria

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Inclusion Criteria

* Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
* Adult males and non-pregnant, non-lactating females
* Documented evidence of chronic HBV infection with detectable hepatitis B surface antigen (HBsAg) levels
* On commercially available HBV OAV treatment(s) for at least 6 months with no change in regimen for 3 months prior to screening
* HBV Deoxyribonucleic acid (DNA) ≤ 20 IU/mL for 6 or more months prior to screening
* Screening Electrocardiogram (ECG) without clinically significant abnormalities

Exclusion Criteria

* Extensive bridging fibrosis or cirrhosis
* Adults meeting any of the protocol defined exclusionary laboratory parameters at screening:

* Alanine aminotransferase (ALT) \> 3x Upper Limit of Normal (ULN)
* International normalized ratio (INR) \> ULN unless the adult is stable on an anticoagulant regimen
* Albumin \< 3.5 g/dL
* Direct bilirubin \> 1.5x ULN
* Platelet Count \< 100,000/uL
* Estimated creatinine clearance \< 60 mL/min (using the Cockcroft-Gault method)
* Co-infection with human immunodeficiency virus, hepatitis C virus or hepatitis D virus
* Prior history of hepatocellular carcinoma (HCC) or screening alpha-fetoprotein ≥ 50 ng/mL without imaging
* Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease, hemoglobinopathy, retinal disease, or are immunosuppressed.
* Chronic liver disease of a non-HBV etiology, except for non-alcoholic fatty liver disease
* Received solid organ or bone marrow transplant
* Received prolonged therapy with immunomodulators or biologics within 3 months of screening
* Use of another investigational agent within 90 days of screening, unless allowed by the Sponsor
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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University of Maryland, Institute of Human Virology

Baltimore, Maryland, United States

Site Status

Auckland Clinical Studies Limited

Auckland, , New Zealand

Site Status

Countries

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United States New Zealand

References

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Brooks AE, Verdon D, Eom J, Ng J, Steemson H, Lau AH, et al. Peripheral Immune Responses to Toll-Like Receptor 8 Agonist Selgantolimod (GS-9688) in Patients with Chronic Hepatitis B [Poster]. AASLD: The Liver Meeting® 2019; 2019 08-12 November; Boston, MA.

Reference Type RESULT

Gane E, Zhao Y, Tan SK, Lau AH, Gaggar A, Subramanian M, et al. Efficacy and Safety of Oral TLR8 Agonist Selgantolimod in Virally Suppressed Adult Patients With Chronic Hepatitis B: a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study [Poster 697]. AASLD: The Liver Meeting® 2019; 2019 08-12 November; Boston, MA.

Reference Type RESULT

Chen DY, C. M, Tan SK, Yang JC, Gane EJ, Janssen HLA, et al. Characterization of Cytokine Response to Toll-Like Receptor 8 Agonist Selgantolimod in Viremic and Virally Suppressed Chronic Hepatitis B Patients [Poster 0721]. American Association for the Study of Liver Diseases (AASLD): The Liver Meeting Digital Experience; 2020 13-16 November.

Reference Type RESULT

Chen D, Kim S, Brooks A, McDonald C, Yang J, Gaggar A, et al. Potential Biomarkers of Response in Chronic Hepatitis B Patients Who Achieved HBeAg Loss Upon Treatment With Toll-Like Receptor 8 Agonist Selgantolimod [Poster FR1350]. The Digital International Liver Congress (ILC); 2020 27-29 August.

Reference Type RESULT

Gane E, Dubar PR, Brooks AE, Zhao Y, Tan SK, Lau AH, et al. Efficacy and Safety of 24 Weeks Treatment with Oral TLR8 Agonist Selgantolimod (GS-9688, SLGN) in Virally Suppressed Adult Patients with Chronic Hepatitis B: A Phase 2 Study [Presentation]. The Digital International Liver Congress (ILC); 2020 27-29 August.

Reference Type RESULT

Gane EJ, Dunbar PR, Brooks AE, Zhang F, Chen D, Wallin JJ, van Buuren N, Arora P, Fletcher SP, Tan SK, Yang JC, Gaggar A, Kottilil S, Tang L. Safety and efficacy of the oral TLR8 agonist selgantolimod in individuals with chronic hepatitis B under viral suppression. J Hepatol. 2023 Mar;78(3):513-523. doi: 10.1016/j.jhep.2022.09.027. Epub 2022 Oct 29.

Reference Type DERIVED
PMID: 38133554 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Week 24 Analysis and Final Analysis

View Document

Document Type: Statistical Analysis Plan: TFFU (Treatment-Free Follow-Up) Analysis

View Document

Other Identifiers

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ACTRN12618000143224p

Identifier Type: REGISTRY

Identifier Source: secondary_id

GS-US-389-2024

Identifier Type: -

Identifier Source: org_study_id

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