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

Primary Purpose

Chronic Hepatitis B

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Selgantolimod

Placebo

Hepatitis B virus (HBV) OAV Therapy

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key 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

Key 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

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

Sites / Locations

University of Maryland, Institute of Human Virology
Auckland Clinical Studies Limited

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Selgantolimod 3 mg: HBeAg-positive CHB Participants

Selgantolimod 3 mg: HBeAg-negative CHB Participants

Selgantolimod 1.5 mg: HBeAg-positive CHB Participants

Selgantolimod 1.5 mg: HBeAg-negative CHB Participants

Placebo: HBeAg-positive CHB Participants

Placebo: HBeAg-negative CHB Participants

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24

Secondary Outcome Measures

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48

Change From Baseline in Serum qHBsAg at Week 4

Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8

Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12

Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24

Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48

Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12

HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

Percentage of Participants With HBsAg Loss at Week 24

HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

Percentage of Participants With HBsAg Loss at Week 48

HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

Percentage of Participants With HBeAg Loss and Seroconversion at Week 12

HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit.

Percentage of Participants With HBeAg Loss and Seroconversion at Week 24

Percentage of Participants With HBeAg Loss and Seroconversion at Week 48

HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as hepatitis B e antibody (HBeAb) test changing from negative or missing at baseline to positive at a postbaseline visit.

Percentage of Participants With Virologic Breakthrough

Virologic breakthrough was defined as having two consecutive visits of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 69 IU/mL.

Percentage of Participants With Drug Resistance Mutations

The criteria for a drug resistance mutation was having two consecutive visits of HBV DNA ≥ 69 IU/mL.

Full Information

NCT ID

NCT03491553

First Posted

April 2, 2018

Last Updated

July 27, 2021

Sponsor

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03491553

Brief Title

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

Official Title

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Virally-Suppressed Adult Subjects With Chronic Hepatitis B

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

April 6, 2018 (Actual)

Primary Completion Date

March 22, 2019 (Actual)

Study Completion Date

August 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Selgantolimod 3 mg: HBeAg-positive CHB Participants

Arm Type

Experimental

Arm Description

Arm Title

Selgantolimod 3 mg: HBeAg-negative CHB Participants

Arm Type

Experimental

Arm Description

Arm Title

Selgantolimod 1.5 mg: HBeAg-positive CHB Participants

Arm Type

Experimental

Arm Description

Arm Title

Selgantolimod 1.5 mg: HBeAg-negative CHB Participants

Arm Type

Experimental

Arm Description

Arm Title

Placebo: HBeAg-positive CHB Participants

Arm Type

Experimental

Arm Description

Arm Title

Placebo: HBeAg-negative CHB Participants

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Selgantolimod

Other Intervention Name(s)

GS-9688

Intervention Description

Tablet(s) administered orally once weekly

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Hepatitis B virus (HBV) OAV Therapy

Intervention Description

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®)

Primary Outcome Measure Information:

Title

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4

Time Frame

Week 4

Title

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8

Time Frame

Week 8

Title

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12

Time Frame

Week 12

Title

Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48

Time Frame

Week 48

Title

Change From Baseline in Serum qHBsAg at Week 4

Time Frame

Baseline, Week 4

Title

Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8

Time Frame

Baseline, Week 8

Title

Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12

Time Frame

Baseline, Week 12

Title

Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24

Time Frame

Baseline, Week 24

Title

Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48

Time Frame

Baseline, Week 48

Title

Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12

Description

HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

Time Frame

Week 12

Title

Percentage of Participants With HBsAg Loss at Week 24

Description

HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

Time Frame

Week 24

Title

Percentage of Participants With HBsAg Loss at Week 48

Description

HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

Time Frame

Week 48

Title

Percentage of Participants With HBeAg Loss and Seroconversion at Week 12

Description

Time Frame

Week 12

Title

Percentage of Participants With HBeAg Loss and Seroconversion at Week 24

Description

Time Frame

Week 24

Title

Percentage of Participants With HBeAg Loss and Seroconversion at Week 48

Description

Time Frame

Week 48

Title

Percentage of Participants With Virologic Breakthrough

Description

Virologic breakthrough was defined as having two consecutive visits of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 69 IU/mL.

Time Frame

Baseline up to Week 48

Title

Percentage of Participants With Drug Resistance Mutations

Description

The criteria for a drug resistance mutation was having two consecutive visits of HBV DNA ≥ 69 IU/mL.

Time Frame

Baseline up to Week 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key 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 Key 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 NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gilead Study Director

Organizational Affiliation

Gilead Sciences

Official's Role

Study Director

Facility Information:

Facility Name

University of Maryland, Institute of Human Virology

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

Auckland Clinical Studies Limited

City

Auckland

ZIP/Postal Code

1010

Country

New Zealand

12. IPD Sharing Statement

Plan to Share IPD

Citations:

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Citation

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.

Results Reference

result

Learn more about this trial

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

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