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

Phase 2

Completed

Conditions: Chronic Hepatitis B

Interventions: Drug: Placebo
Drug: Selgantolimod
Drug: TAF

Registration Number: NCT03615066

Lead Sponsor: Gilead Sciences

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 67

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + TAF	Placebo	Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive 2 tablets of placebo on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, placebo will be discontinued, and participants will continue to receive TAF 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.
Selgantolimod 3 mg + TAF	TAF	Participants with Hepatitis B e antigen (HBeAg)-positive CHB or HBeAg-negative CHB currently not on oral antiviral (OAV) treatment, will receive selgantolimod 3 mg (2 x 1.5 mg tablet) on the same day once weekly for 24 doses along with tenofovir alafenamide (TAF) 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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.
Selgantolimod 1.5 mg + TAF	Placebo	Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) and placebo (1 tablet) on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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.
Placebo + TAF	TAF	Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive 2 tablets of placebo on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, placebo will be discontinued, and participants will continue to receive TAF 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.
Selgantolimod 1.5 mg + TAF	TAF	Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) and placebo (1 tablet) on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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.
Selgantolimod 3 mg + TAF	Selgantolimod	Participants with Hepatitis B e antigen (HBeAg)-positive CHB or HBeAg-negative CHB currently not on oral antiviral (OAV) treatment, will receive selgantolimod 3 mg (2 x 1.5 mg tablet) on the same day once weekly for 24 doses along with tenofovir alafenamide (TAF) 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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.
Selgantolimod 1.5 mg + TAF	Selgantolimod	Participants with HBeAg-positive CHB or HBeAg-negative CHB currently not on OAV treatment, will receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) and placebo (1 tablet) on the same day once weekly for 24 doses along with TAF 25 mg once daily for 24 weeks. After the 24th dose, selgantolimod will be discontinued, and participants will continue to receive TAF 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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24	Baseline, Week 24
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	First dose date up to Week 24 plus 30 days	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.
Percentage of Participants With Treatment-Emergent Laboratory Abnormalities	First dose date up to Week 24 plus 30 days	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12	Week 12	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Percentage of Participants With HBeAg Loss and Seroconversion at Week 12	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.
Change From Baseline in Serum qHBsAg at Week 12	Baseline, Week 12
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8	Baseline, Week 8
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4	Baseline, Week 4
Change From Baseline in Serum qHBsAg at Week 48	Baseline, Week 48
Percentage of Participants With HBV DNA < LLOQ at Week 48	Week 48	LLOQ was defined as 20 IU/mL.
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12	Baseline, Week 12
Change From Baseline in Serum qHBsAg at Week 4	Baseline, Week 4
Change From Baseline in Serum qHBsAg at Week 8	Baseline, Week 8
Percentage of Participants With HBsAg Loss at Week 48	Week 48	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Percentage of Participants With HBeAg Loss and Seroconversion at Week 48	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.
Percentage of Participants With Drug Resistance Mutations	Baseline up to Week 48
PK Parameter: Tmax of Selgantolimod	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23	Tmax is defined as the time (observed time point) of Cmax.
Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48	Baseline, Week 48
Change From Baseline in Serum qHBsAg at Week 24	Baseline, Week 24
Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12	Week 12	LLOQ was defined as 20 IU/mL.
Percentage of Participants With HBV DNA < LLOQ at Week 24	Week 24	LLOQ was defined as 20 IU/mL.
PK Parameter: AUC0-24 of Selgantolimod	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23	AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hours.
PK Parameter: AUCinf of Selgantolimod	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23	AUC0-inf is defined as the concentration of drug over time from time zero to infinity.
PK Parameter: CL/F of Selgantolimod	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23	CL/F is defined as the apparent oral clearance following administration of the drug.
Percentage of Participants With HBsAg Loss at Week 24	Week 24	HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit.
Percentage of Participants With HBeAg Loss and Seroconversion at Week 24	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.
Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23	AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Percentage of Participants With Virologic Breakthrough From Baseline up to Week 24	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.
Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48	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.
PK Parameter: t1/2 of Selgantolimod	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: Cmax of Selgantolimod	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23	Cmax is defined as the maximum concentration of drug.

Trial Locations

Locations (10): University Health Network, Toronto General Hospital, Toronto Centre for Liver Disease
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Toronto, Ontario, Canada
Toronto Liver Centre
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Toronto, Ontario, Canada
Chung-Ang University Hospital
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Seoul, Korea, Republic of
Seoul National University Hospital
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Seoul, Korea, Republic of
Asan Medical Center
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Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
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Seoul, Korea, Republic of
National Taiwan University Hospital
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Taipei City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
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Kaohsiung, Taiwan
E-Da Hospital
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Kaohsiung City, Taiwan
University of Calgary Liver Unit - Heritage Medical Research Clinic
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Calgary, Alberta, Canada