NCT03491553

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2018

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 2, 2018

Completed
4 days until next milestone

Study Start

First participant enrolled

April 6, 2018

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 9, 2018

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 22, 2019

Completed
1 year until next milestone

Results Posted

Study results publicly available

April 1, 2020

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 10, 2020

Completed
Last Updated

August 19, 2021

Status Verified

July 1, 2021

Enrollment Period

12 months

First QC Date

April 2, 2018

Results QC Date

March 18, 2020

Last Update Submit

July 27, 2021

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

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

    Week 24

Secondary Outcomes (17)

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

    Week 4

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

    Week 8

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

    Week 12

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

    Week 48

  • Change From Baseline in Serum qHBsAg at Week 4

    Baseline, Week 4

  • +12 more secondary outcomes

Study Arms (6)

Selgantolimod 3 mg: HBeAg-positive CHB Participants

EXPERIMENTAL

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.

Drug: SelgantolimodDrug: Hepatitis B virus (HBV) OAV Therapy

Selgantolimod 3 mg: HBeAg-negative CHB Participants

EXPERIMENTAL

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.

Drug: SelgantolimodDrug: Hepatitis B virus (HBV) OAV Therapy

Selgantolimod 1.5 mg: HBeAg-positive CHB Participants

EXPERIMENTAL

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.

Drug: SelgantolimodDrug: PlaceboDrug: Hepatitis B virus (HBV) OAV Therapy

Selgantolimod 1.5 mg: HBeAg-negative CHB Participants

EXPERIMENTAL

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.

Drug: SelgantolimodDrug: PlaceboDrug: Hepatitis B virus (HBV) OAV Therapy

Placebo: HBeAg-positive CHB Participants

EXPERIMENTAL

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.

Drug: PlaceboDrug: Hepatitis B virus (HBV) OAV Therapy

Placebo: HBeAg-negative CHB Participants

EXPERIMENTAL

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.

Drug: PlaceboDrug: Hepatitis B virus (HBV) OAV Therapy

Interventions

SelgantolimodDRUG

Tablet(s) administered orally once weekly

Also known as: GS-9688
Selgantolimod 1.5 mg: HBeAg-negative CHB ParticipantsSelgantolimod 1.5 mg: HBeAg-positive CHB ParticipantsSelgantolimod 3 mg: HBeAg-negative CHB ParticipantsSelgantolimod 3 mg: HBeAg-positive CHB Participants
PlaceboDRUG

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

Placebo: HBeAg-negative CHB ParticipantsPlacebo: HBeAg-positive CHB ParticipantsSelgantolimod 1.5 mg: HBeAg-negative CHB ParticipantsSelgantolimod 1.5 mg: HBeAg-positive CHB Participants
Hepatitis B virus (HBV) OAV TherapyDRUG

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 ParticipantsPlacebo: HBeAg-positive CHB ParticipantsSelgantolimod 1.5 mg: HBeAg-negative CHB ParticipantsSelgantolimod 1.5 mg: HBeAg-positive CHB ParticipantsSelgantolimod 3 mg: HBeAg-negative CHB ParticipantsSelgantolimod 3 mg: HBeAg-positive CHB Participants

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Extensive bridging fibrosis or cirrhosis
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of Maryland, Institute of Human Virology

Baltimore, Maryland, 21201, United States

Location

Auckland Clinical Studies Limited

Auckland, 1010, New Zealand

Location

Related Publications (6)

  • 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.

    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.

    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.

    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.

    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.

    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.

    PMID: 38133554DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

selgantolimodHepatitis B Vaccines

Condition Hierarchy (Ancestors)

Hepatitis BBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Viral Hepatitis VaccinesViral VaccinesVaccinesBiological ProductsComplex Mixtures

Results Point of Contact

Title
Gilead Clinical Study Information Center
Organization
Gilead Sciences
GileadClinicalTrials@gilead.com
1-833-445-3230 (GILEAD-0)

Study Officials

  • Gilead Study Director

    Gilead Sciences

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 2, 2018

First Posted

April 9, 2018

Study Start

April 6, 2018

Primary Completion

March 22, 2019

Study Completion

August 10, 2020

Last Updated

August 19, 2021

Results First Posted

April 1, 2020

Record last verified: 2021-07

Data Sharing

IPD Sharing
Will not share

Locations

NZ(1)US(1)