Clinical trial NCT03491553: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2018-04-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4
timeFrame: Week 4
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8
timeFrame: Week 8
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12
timeFrame: Week 12
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48
timeFrame: Week 48
measure: Change From Baseline in Serum qHBsAg at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12
timeFrame: Week 12
measure: Percentage of Participants With HBsAg Loss at Week 24
timeFrame: Week 24
measure: Percentage of Participants With HBsAg Loss at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBeAg Loss and Seroconversion at Week 12
timeFrame: Week 12
measure: Percentage of Participants With HBeAg Loss and Seroconversion at Week 24
timeFrame: Week 24
measure: Percentage of Participants With HBeAg Loss and Seroconversion at Week 48
timeFrame: Week 48
measure: Percentage of Participants With Virologic Breakthrough
timeFrame: Baseline up to Week 48
measure: Percentage of Participants With Drug Resistance Mutations
timeFrame: Baseline up to Week 48
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland, Institute of Human Virology
state: Maryland
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies Limited
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.