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

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 Viremic Adult Subjects With Chronic Hepatitis B Who Are Not Currently on Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03615066
• Other study ID #: GS-US-389-2025
• Status: Completed
• Phase: Phase 2
• Start date: August 28, 2018
• Est. completion date: April 12, 2021

Study information

• Verified date: April 2022
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: April 12, 2021
• Est. primary completion date: December 12, 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 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Placebo
Tablet(s) administered orally every 7 days for 24 doses in fasted state
• Selgantolimod
Tablet(s) administered orally every 7 days for 24 doses in fasted state
• TAF
Tablet(s) administered orally once daily with food

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

Canada,  Korea, Republic of,  Taiwan, 

References & Publications (3)

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]. The Digital International Liver Conference 2020 27-29 August.

Janssen H, Lampertico P, Chen C-Y, Heo J, Foumier C, Ahn S, et al. Safety and Efficacy of Switching to Tenofovir Alafenamide in Virally Suppressed Chronic Hepatitis B Patients With Renal Impairment: Week-48 Results From a Phase 2 Open-label Study [Poster]. The Digital International Liver Conference 2020 27-29 August.

Janssen H, Lim Y-S, Kim HJ, Tseng C-H, Coffin C, Elkashab M, et al. Safety and Efficacy of Oral TLR8 Agonist Selgantolimod in Viremic Adult Patients With Chronic Hepatitis B [Poster]. International Liver Congress 2021 23-26 June.

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		Baseline, Week 24
Primary	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.	First dose date up to Week 24 plus 30 days
Primary	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.	First dose date up to Week 24 plus 30 days
Secondary	Percentage of Participants With = 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4		Baseline, Week 4
Secondary	Percentage of Participants With = 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8		Baseline, Week 8
Secondary	Percentage of Participants With = 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12		Baseline, Week 12
Secondary	Percentage of Participants With = 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48		Baseline, Week 48
Secondary	Change From Baseline in Serum qHBsAg at Week 4		Baseline, Week 4
Secondary	Change From Baseline in Serum qHBsAg at Week 8		Baseline, Week 8
Secondary	Change From Baseline in Serum qHBsAg at Week 12		Baseline, Week 12
Secondary	Change From Baseline in Serum qHBsAg at Week 24		Baseline, Week 24
Secondary	Change From Baseline in Serum qHBsAg at Week 48		Baseline, Week 48
Secondary	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.	Week 12
Secondary	Percentage of Participants With HBV DNA < LLOQ at Week 24	LLOQ was defined as 20 IU/mL.	Week 24
Secondary	Percentage of Participants With HBV DNA < LLOQ at Week 48	LLOQ was defined as 20 IU/mL.	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 Hepatitis B e antibody (HBeAb) loss and anti-HBe change from negative/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 loss and anti-HBe change from negative/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 HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit.	Week 48
Secondary	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.	Baseline up to Week 24
Secondary	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.	Baseline up to Week 48
Secondary	Percentage of Participants With Drug Resistance Mutations		Baseline up to Week 48
Secondary	Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Secondary	PK Parameter: AUC0-24 of Selgantolimod	AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hours.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Secondary	PK Parameter: AUCinf of Selgantolimod	AUC0-inf is defined as the concentration of drug over time from time zero to infinity.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Secondary	PK Parameter: Cmax of Selgantolimod	Cmax is defined as the maximum concentration of drug.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Secondary	PK Parameter: Tmax of Selgantolimod	Tmax is defined as the time (observed time point) of Cmax.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Secondary	PK Parameter: CL/F of Selgantolimod	CL/F is defined as the apparent oral clearance following administration of the drug.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Secondary	PK Parameter: t1/2 of Selgantolimod	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23