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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03491553
• Other study ID #: GS-US-389-2024
• Secondary ID: ACTRN12618000143
• Status: Completed
• Phase: Phase 2
• Start date: April 6, 2018
• Est. completion date: August 10, 2020

Study information

• Verified date: July 2021
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: August 10, 2020
• Est. primary completion date: March 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Selgantolimod
Tablet(s) administered orally once weekly
• Placebo
Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly
• 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®)

Locations

Country	Name	City	State
New Zealand	Auckland Clinical Studies Limited	Auckland
United States	University of Maryland, Institute of Human Virology	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  New Zealand, 

References & Publications (5)

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

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 Internationa

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 Stu

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 D

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 Stud

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants With = 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4		Week 4
Secondary	Percentage of Participants With = 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8		Week 8
Secondary	Percentage of Participants With = 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12		Week 12
Secondary	Percentage of Participants With = 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48		Week 48
Secondary	Change From Baseline in Serum qHBsAg at Week 4		Baseline, Week 4
Secondary	Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8		Baseline, Week 8
Secondary	Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12		Baseline, Week 12
Secondary	Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24		Baseline, Week 24
Secondary	Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48		Baseline, Week 48
Secondary	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.	Week 12
Secondary	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.	Week 24
Secondary	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.	Week 48
Secondary	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.	Week 12
Secondary	Percentage of Participants With HBeAg Loss and Seroconversion at 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.	Week 24
Secondary	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.	Week 48
Secondary	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.	Baseline up to Week 48
Secondary	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.	Baseline up to Week 48