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

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ClinicalTrials.gov Identifier: NCT03491553
Recruitment Status : Completed
First Posted : April 9, 2018
Results First Posted : April 1, 2020
Last Update Posted : September 22, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: Selgantolimod Drug: Placebo Drug: Hepatitis B virus (HBV) OAV Therapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : April 6, 2018
Actual Primary Completion Date : March 22, 2019
Actual Study Completion Date : August 10, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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).
Drug: Selgantolimod
Tablet(s) administered orally once weekly
Other Name: GS-9688

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®)


Experimental: 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.
Drug: Selgantolimod
Tablet(s) administered orally once weekly
Other Name: GS-9688

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®)


Experimental: 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.
Drug: Selgantolimod
Tablet(s) administered orally once weekly
Other Name: GS-9688

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

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®)


Experimental: 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.
Drug: Selgantolimod
Tablet(s) administered orally once weekly
Other Name: GS-9688

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

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®)


Experimental: 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.
Drug: Placebo
Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly

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®)


Experimental: 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.
Drug: Placebo
Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly

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®)





Primary Outcome Measures :
  1. 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 Measures :
  1. Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4 [ Time Frame: Week 4 ]
  2. Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8 [ Time Frame: Week 8 ]
  3. Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12 [ Time Frame: Week 12 ]
  4. Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48 [ Time Frame: Week 48 ]
  5. Change From Baseline in Serum qHBsAg at Week 4 [ Time Frame: Baseline, Week 4 ]
  6. Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8 [ Time Frame: Baseline, Week 8 ]
  7. Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12 [ Time Frame: Baseline, Week 12 ]
  8. Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24 [ Time Frame: Baseline, Week 24 ]
  9. Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48 [ Time Frame: Baseline, Week 48 ]
  10. Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12 [ Time Frame: Week 12 ]
    HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

  11. Percentage of Participants With HBsAg Loss at Week 24 [ Time Frame: Week 24 ]
    HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

  12. Percentage of Participants With HBsAg Loss at Week 48 [ Time Frame: Week 48 ]
    HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.

  13. Percentage of Participants With HBeAg Loss and Seroconversion at Week 12 [ Time Frame: 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.

  14. Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 [ Time Frame: Week 24 ]
    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.

  15. Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 [ Time Frame: 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.

  16. Percentage of Participants With Virologic Breakthrough [ Time Frame: Baseline up to Week 48 ]
    Virologic breakthrough was defined as having two consecutive visits of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 69 IU/mL.

  17. Percentage of Participants With Drug Resistance Mutations [ Time Frame: Baseline up to Week 48 ]
    The criteria for a drug resistance mutation was having two consecutive visits of HBV DNA ≥ 69 IU/mL.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03491553


Locations
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United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201
New Zealand
Auckland Clinical Studies Limited
Auckland, New Zealand, 1010
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] August 27, 2019
Statistical Analysis Plan  [PDF] January 18, 2019

Publications of Results:
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.
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.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03491553    
Other Study ID Numbers: GS-US-389-2024
ACTRN12618000143224p ( Registry Identifier: ANZCTR )
First Posted: April 9, 2018    Key Record Dates
Results First Posted: April 1, 2020
Last Update Posted: September 22, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections