Clinical trial NCT03615066: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2018-08-03
Enrollment: 67
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 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.


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 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.

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: Baseline, Week 24
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to Week 24 plus 30 days
measure: Percentage of Participants With Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to Week 24 plus 30 days
Secondary outcomes:
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4
timeFrame: Baseline, Week 4
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8
timeFrame: Baseline, Week 8
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in Serum qHBsAg at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in Serum qHBsAg at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in Serum qHBsAg at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in Serum qHBsAg at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Serum qHBsAg at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) < Lower Limit of Quantification (LLOQ) at Week 12
timeFrame: Week 12
measure: Percentage of Participants With HBV DNA < LLOQ at Week 24
timeFrame: Week 24
measure: Percentage of Participants With HBV DNA < LLOQ at Week 48
timeFrame: 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 From Baseline up to Week 24
timeFrame: Baseline up to Week 24
measure: Percentage of Participants With Virologic Breakthrough From Baseline up to Week 48
timeFrame: Baseline up to Week 48
measure: Percentage of Participants With Drug Resistance Mutations
timeFrame: Baseline up to Week 48
measure: Pharmacokinetic (PK) Parameter: AUClast of Selgantolimod
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
measure: PK Parameter: AUC0-24 of Selgantolimod
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
measure: PK Parameter: AUCinf of Selgantolimod
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
measure: PK Parameter: Cmax of Selgantolimod
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
measure: PK Parameter: Tmax of Selgantolimod
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
measure: PK Parameter: CL/F of Selgantolimod
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
measure: PK Parameter: t1/2 of Selgantolimod
timeFrame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose at Day 1 and Week 23
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary Liver Unit - Heritage Medical Research Clinic
state: Alberta
city: Toronto
country: Canada
facility: University Health Network, Toronto General Hospital, Toronto Centre for Liver Disease
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Kaohsiung City
country: Taiwan
facility: E-Da Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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]. The Digital International Liver Conference 2020 27-29 August.
citation: 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.
citation: 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.