Study to Evaluate the Safety, Tolerability, and Antiviral Activity of Selgantolimod (Formerly GS-9688) in Viremic Adult Participants With Chronic Hepatitis B (CHB) Who Are Not Currently on Treatment

Gilead Sciences67 enrolled

Overview

The primary objectives of this study are to evaluate the safety and tolerability of multiple oral doses of selgantolimod and to evaluate the antiviral activity of selgantolimod in adult participants with chronic hepatitis B (CHB) who are viremic and not currently being treated.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Chronic Hepatitis B

Interventions

PlaceboDRUG

Tablet(s) administered orally every 7 days for 24 doses in fasted state

SelgantolimodDRUG

Tablet(s) administered orally every 7 days for 24 doses in fasted state

TAFDRUG

Tablet(s) administered orally once daily with food

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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 male and non-pregnant, non-lactating females * Documented evidence of chronic hepatitis B virus (HBV) infection with detectable hepatitis B surface antigen (HBsAg) levels at screening * Screening HBV deoxyribonucleic acid (DNA) ≥ 2000 international units per milliliter (IU/mL). * Screening electrocardiogram (ECG) without clinically significant abnormalities Key Exclusion Criteria: * Extensive bridging fibrosis or cirrhosis * Received a commercially available HBV OAV treatment(s) within the 3 months prior to screening. * Received prolonged therapy with immunomodulators or biologics within 3 months of screening * Individuals meeting any of the following laboratory parameters at screening: * Alanine aminotransferase \> 5 \* upper limit of normal (ULN) * International normalized ratio \> ULN unless the individual is stable on an anticoagulant regimen * Albumin \< 3.5 g/dL * Direct bilirubin \>1.5x ULN * Platelet Count \< 100,000/µL * Estimated creatinine clearance \< 60 mL/min (using the Cockcroft-Gault method) * Co-infection with human immunodeficiency virus (HIV), hepatitis C virus or hepatitis D virus * Prior history of hepatocellular carcinoma 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. * Use of another investigational agent within 90 days of screening, unless allowed by the sponsor. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (10)

University of Calgary Liver Unit - Heritage Medical Research Clinic

Calgary, Alberta, Canada

University Health Network, Toronto General Hospital, Toronto Centre for Liver Disease

Toronto, Ontario, Canada

Toronto Liver Centre

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

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

Time frame: Baseline, Week 24

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE was any unfavorable and unintended sign, symptom, disease, and/or laboratory or physiological observation that may or may not be related to the investigational medicinal product. A TEAE was defined as any AE with an onset date on or after the first dose date and no later than 30 days after permanent discontinuation of selgantolimod/placebo; or any AE leading to premature discontinuation of study drugs.

Time frame: First dose date up to Week 24 plus 30 days

Percentage of Participants With Treatment-Emergent Laboratory Abnormalities

Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of the last dose of study drug plus 30 days for selgantolimod/placebo at Week 24. If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Clinical laboratory results were graded according to Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities.

Time frame: First dose date up to Week 24 plus 30 days

Secondary Outcomes

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

Time frame: Baseline, Week 4

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

Time frame: Baseline, Week 8

Data from ClinicalTrials.gov

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Seoul National University Hospital

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

Chung-Ang University Hospital

Seoul, South Korea

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

E-Da Hospital

Kaohsiung City, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

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

Time frame: Baseline, Week 12

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

Time frame: Baseline, Week 48

Change From Baseline in Serum qHBsAg at Week 4

Time frame: Baseline, Week 4

Change From Baseline in Serum qHBsAg at Week 8

Time frame: Baseline, Week 8

Change From Baseline in Serum qHBsAg at Week 12

Time frame: Baseline, Week 12

Change From Baseline in Serum qHBsAg at Week 24

Time frame: Baseline, Week 24

Change From Baseline in Serum qHBsAg at Week 48

Time frame: Baseline, Week 48

Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12

LLOQ was defined as 20 IU/mL.

Time frame: Week 12

Percentage of Participants With HBV DNA < LLOQ at Week 24

LLOQ was defined as 20 IU/mL.

Time frame: Week 24

Percentage of Participants With HBV DNA < LLOQ at Week 48

LLOQ was defined as 20 IU/mL.

Time frame: 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.

Time frame: Week 12

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.

Time frame: Week 24

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.

Time frame: Week 48

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 Hepatitis B e antibody (HBeAb) loss and anti-HBe change from negative/missing at baseline to positive at a postbaseline visit.

Time frame: Week 12

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 loss and anti-HBe change from negative/missing at baseline to positive at a postbaseline visit.

Time frame: 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 HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit.

Time frame: Week 48

Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24

Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having been \< 69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir.

Time frame: Baseline up to Week 24

Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48

Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having been \< 69 IU/mL or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir.

Time frame: Baseline up to Week 48

Percentage of Participants With Drug Resistance Mutations

Time frame: Baseline up to Week 48

Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod

AUClast is defined as the concentration of drug from time zero to the last observable concentration.