Study to Evaluate the Safety, Tolerability, and Efficacy of Vesatolimod in Combination With Tenofovir Disoproxil Fumarate (TDF) in Adults With Chronic Hepatitis B (CHB) Infection Who Are Currently Not Being Treated

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod (formerly GS-9620) in adults with chronic hepatitis B (CHB) infection who are currently not being treated.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: TDF; Drug: Placebo; Drug: Vesatolimod

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
• Hong Kong
  • Kowloon, Hong Kong
• Italy
  • Bologna, Italy
  • Milano, Italy
  • Pisa, Italy
  • San Giovanni Rotondo, Italy
• Korea, Republic of
  • Daegu, Korea, Republic of
  • Seoul, Korea, Republic of
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand
• Taiwan
  • Dalin, Taiwan
  • Kaohsiung, Taiwan
• United Kingdom
  • London, United Kingdom
• United States
  • California
    • Los Angeles, California, United States
    • Palo Alto, California, United States
    • San Diego, California, United States
    • San Francisco, California, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Maryland
    • Catonsville, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • New York
    • Flushing, New York, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Adult males or females between the ages of 18-65
• Chronic hepatitis B virus (HBV) infection
• HBV deoxyribonucleic acid (DNA ) ≥ 2000 IU/mL at screening

Key Exclusion Criteria:

• Extensive bridging fibrosis or cirrhosis
• Received oral antiviral treatment for HBV or prolonged therapy with immune-modulators or biologics within 3 months of screening
• Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV) or hepatitis D virus (HDV)
• Chronic liver disease other than HBV
• Lactating or pregnant females or those that wish to become pregnant during the course of the study

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: TDF + placebo; Main Study Phase: Tenofovir disoproxil fumarate (TDF) 300 mg tablets orally once daily for up to 48 weeks + placebo administered orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.	Drug: TDF; 300 mg tablets administered orally once daily; Other Names: Viread®; Drug: Placebo; Placebo administered orally once a week (every 7 days) for 12 doses
Experimental: TDF + Vesatolimod 1 mg; Main Study Phase:TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 1 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.	Drug: TDF; 300 mg tablets administered orally once daily; Other Names: Viread®; Drug: Vesatolimod; Tablets administered orally once a week (every 7 days) for 12 doses; Other Names: GS-9620
Experimental: TDF + Vesatolimod 2 mg; Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 2 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.	Drug: TDF; 300 mg tablets administered orally once daily; Other Names: Viread®; Drug: Vesatolimod; Tablets administered orally once a week (every 7 days) for 12 doses; Other Names: GS-9620
Experimental: TDF + Vesatolimod 4 mg; Main Study Phase: TDF 300 mg tablets orally once daily for up to 48 weeks + vesatolimod 4 mg tablet orally once a week (every 7 days) for 12 doses. Optional Treatment Extension Phase: At Week 48 participants had the option to continue TDF 300 mg tablets orally once daily up to Week 144.	Drug: TDF; 300 mg tablets administered orally once daily; Other Names: Viread®; Drug: Vesatolimod; Tablets administered orally once a week (every 7 days) for 12 doses; Other Names: GS-9620

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change (Measured in log10 IU/mL) in Hepatitis B Surface Antigen (HBsAg) From Baseline at Week 24	The change from baseline to Week 24 in HBsAg (log10 IU/mL) was analyzed using a mixed model for repeated measures (MMRM). The model included treatment, baseline HBsAg (log10 IU/mL), baseline Hepatitis B Envelope Antigen (HBeAg) status (positive or negative), baseline alanine aminotransferase (ALT) level relative to upper limit of normal (ULN) (> 19 vs ≤ 19 IU/L for females; > 30 vs ≤ 30 IU/L for males), visit and treatment-by-visit interaction as fixed effects, and visit as a repeated measure.	Baseline; Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HBeAg Loss and Seroconversion at Week 24	HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative Hepatitis B Envelope Antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.	Week 24
Percentage of Participants With HBeAg Loss and Seroconversion at Week 48	HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.	Week 48
Percentage of Participants With HBsAg Loss and Seroconversion at Week 24	HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative Hepatitis B Surface Antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.	Week 24
Percentage of Participants With HBsAg Loss and Seroconversion at Week 48	HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit. The Missing (M) = Failure (F) approach was used for this analysis.	Week 48
Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 12		Baseline; Week 12
Mean Change (Measured in log10 IU/mL) in HBsAg From Baseline at Week 48		Baseline; Week 48
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 12	HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.	Baseline to Week 12
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 24	HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 24 post-baseline visit.	Baseline to Week 24
Percentage of Participants With a ≥ 0.5 log10 IU/mL Decline in Serum HBsAg Titers From Baseline at Week 48	HBsAg ≥ 0.5 log10 IU/mL decline was defined as a decline from baseline in log10 IU/mL serum HBsAg ≥ 0.5 at the Week 12 post-baseline visit. Missing values were considered failures.	Baseline to Week 48
Percentage of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) < Lower Limit of Quantitation (LLOQ) at Week 24	LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.	Week 24
Percentage of Participants With HBV DNA < LLOQ at Week 48	LLOQ for HBV DNA was defined as 20 IU/mL. The participants with missing information were excluded from the analysis.	Week 48
Percentage of Participants Experiencing Virologic Breakthrough	Virologic breakthrough was defined as confirmed HBV DNA ≥ 69 IU/mL after having had HBV DNA < 69 IU/mL or confirmed 1.0 log10 IU/mL or greater increase in HBV DNA from nadir. Confirmation requires 2 consecutive occurrences of elevation in HBV DNA to > 69 IU/mL after having had HBV DNA < 69 IU/mL or 1.0 log10 IU/mL or greater increases in HBV DNA from nadir.	Weeks 24 and 48
Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase/Reverse Transcriptase (Pol/RT)	Sequence analysis of the HBV pol/RT was attempted for any participant who had HBV DNA ≥ 69 IU/mL at Week 48 or early discontinuation. Results of the alignment of Week 48 and baseline sequence were reported as a change from baseline sequence.	Baseline; Week 48
Pharmacokinetic (PK) Parameter: AUClast of Vesatolimod	AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration.	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
PK Parameter: AUCinf of Vesatolimod	AUCinf is defined as the concentration of drug extrapolated to infinite time.	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
PK Parameter: %AUCexp of Vesatolimod	%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
PK Parameter: Cmax of Vesatolimod	Cmax is defined as the maximum concentration of drug.	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
PK Parameter: Clast of Vesatolimod	Clast is defined as the last observable concentration of drug.	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
PK Parameter: Tmax of Vesatolimod	Tmax is defined as the time (observed time point) of Cmax	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
PK Parameter: Tlast of Vesatolimod	Tlast is defined as the time (observed time point) of Clast.	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
PK Parameter: T1/2 of Vesatolimod	T1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose
PK Parameter: CL/F of Vesatolimod	CL/F is defined as the apparent oral clearance following administration of the drug.	Week 11: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours postdose

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Agarwal K, Ahn SH, Elkhashab M, Lau AH, Gaggar A, Bulusu A, Tian X, Cathcart AL, Woo J, Subramanian GM, Andreone P, Kim HJ, Chuang WL, Nguyen MH. Safety and efficacy of vesatolimod (GS-9620) in patients with chronic hepatitis B who are not currently on antiviral treatment. J Viral Hepat. 2018 Nov;25(11):1331-1340. doi: 10.1111/jvh.12942. Epub 2018 Aug 22.
• Agarwal K, Ahn SH, Elkhashab M, Kim K, Lau AH, Gaggar A, et al. Safety and efficacy ofvesatolimod (GS-9620) in patients with chronic hepatitis B (CHB) who are not currently on antiviral treatment. Poster 930. AASLD 2017. Hepatology; 66:497A 498A, 2017.
• Younossi ZM, Stepanova M, Janssen H, Agarwal K, Nguyen MH, Gane EJ, et al. The impact of treatment of chronic hepatitis B (CHB) on patient reported outcomes (PROs). Poster 1924. AASLD 2017. Hepatology; 66:1020A, 2017.
• Lau A, Joshi A, Nguyen AH, Gaggar A, Patterson SD, Woo J. Peripheral blood immune cell profiling in virally suppressed chronic hepatitis B (CHB) patients and CHB patients not on an oral antiviral therapy. HBV International Meeting 2017.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2015
• Primary Completion (Actual): January 16, 2017
• Study Completion (Actual): May 3, 2019

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 16, 2015
• First Posted (Estimate): October 19, 2015

Study Record Updates

• Last Update Posted (Actual): May 18, 2020
• Last Update Submitted That Met QC Criteria: May 1, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Hepatitis; Liver Disease; HBV
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Vesatolimod
• Other Study ID Numbers: GS-US-283-1062; 2015-002017-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No