Study To Evaluate Safety and Efficacy of Vesatolimod for the Treatment of Chronic Hepatitis B Virus in Virally-Suppressed Participants

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod in participants with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV).

Participants will be randomized in 3 sequential cohorts (Cohorts A, B, and C). Within each cohort, participants will be randomized in a 1:3:3:3 ratio to placebo or one of the doses of vesatolimod (1, 2, or 4 mg).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
    • Toronto, Ontario, Canada, M5G2C4
• Italy
  • Milan, Italy, 20122
  • Parma, Italy, 43126
  • Pisa, Italy, 56124
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 110-744
  • Seoul, Korea, Republic of, 120-752
  • Seoul, Korea, Republic of, 135-710
• Netherlands
  • Rotterdam, Netherlands, 3015 CE
• New Zealand
  • Auckland, New Zealand, 1142
• United States
  • California
    • Los Angeles, California, United States, 90095
    • San Diego, California, United States, 92154
    • San Francisco, California, United States, 94118
    • San Jose, California, United States, 95128
  • Hawaii
    • Honolulu, Hawaii, United States, 96734
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02111
  • Michigan
    • Detroit, Michigan, United States, 48202
  • New York
    • Flushing, New York, United States, 11355

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:

• Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
• Documented evidence of CHB infection (eg, hepatitis B surface antigen [HBsAg] positive for more than 6 months) with detectable HBsAg levels at screening
• Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below lower limit of quantitation (LLOQ), measured at least once, 6 or more months prior to screening, and HBV DNA < 20 IU/mL at screening
• Currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine, or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening
• Willing to provide blood sample for toll-like receptor 7 (TLR-7) and interleukin 28 B (IL28B) single-nucleotide polymorphism (SNP) assessment
• Must be willing and able to comply with all study requirements

Key Exclusion Criteria:

• Extensive bridging fibrosis or cirrhosis
• Laboratory parameters not within defined thresholds for neutropenia, anemia, thrombocytopenia, leukopenia, or other evidence of inadequate liver function
• Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
• Evidence of hepatocellular carcinoma
• Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Participants under evaluation for possible malignancy are not eligible.
• Significant cardiovascular, pulmonary, or neurological disease

• Any of the following conditions that may worsen in response to interferon (IFN):

  • Autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis)
  • Poorly controlled diabetes mellitus
  • Significant psychiatric disorders
  • Thyroid disorder (unless controlled under treatment)
  • Significant pulmonary diseases (eg, chronic obstructive pulmonary disease)
  • Retinal disease
  • Immunodeficiency disorders
• Received solid organ or bone marrow transplant
• Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal Ab, interferon) within 3 months of screening
• Use of another investigational agents within 3 months of screening
• Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
• Females who are pregnant or may wish to become pregnant during 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: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo 4 Weeks (Cohort A); Placebo tablet once a week for 4 weeks	Drug: Placebo; Placebo to match vesatolimod tablet administered orally
EXPERIMENTAL: Vesatolimod 1 mg 4 Weeks (Cohort A); Vesatolimod 1 mg tablet once a week for 4 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620
EXPERIMENTAL: Vesatolimod 2 mg 4 Weeks (Cohort A); Vesatolimod 2 mg tablet once a week for 4 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620
EXPERIMENTAL: Vesatolimod 4 mg 4 Weeks (Cohort A); Vesatolimod 4 mg tablet once a week for 4 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620
PLACEBO_COMPARATOR: Placebo 8 Weeks (Cohort B); Placebo tablet once a week for 8 weeks	Drug: Placebo; Placebo to match vesatolimod tablet administered orally
EXPERIMENTAL: Vesatolimod 1 mg 8 Weeks (Cohort B); Vesatolimod 1 mg tablet once a week for 8 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620
EXPERIMENTAL: Vesatolimod 2 mg 8 Weeks (Cohort B); Vesatolimod 2 mg tablet once a week for 8 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620
EXPERIMENTAL: Vesatolimod 4 mg 8 Weeks (Cohort B); Vesatolimod 4 mg tablet once a week for 8 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620
PLACEBO_COMPARATOR: Placebo 12 Weeks (Cohort C); Placebo tablet once a week for 12 weeks	Drug: Placebo; Placebo to match vesatolimod tablet administered orally
EXPERIMENTAL: Vesatolimod 1 mg 12 Weeks (Cohort C); Vesatolimod 1 mg tablet once a week for 12 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620
EXPERIMENTAL: Vesatolimod 2 mg 12 Weeks (Cohort C); Vesatolimod 2 mg tablet once a week for 12 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620
EXPERIMENTAL: Vesatolimod 4 mg 12 Weeks (Cohort C); Vesatolimod 4 mg tablet once a week for 12 weeks	Drug: Vesatolimod; Vesatolimod tablet administered orally; Other Names: GS-9620

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24	A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.	Week 24
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (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 within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. Only participants who were HBeAg+ at baseline were included.	Week 48
Composite Endpoint Measuring the 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 within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.	Week 24
Composite Endpoint Measuring the 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 within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.	Week 48
Change From Baseline in Serum HBsAg Level at Week 4		Baseline; Week 4
Change From Baseline in Serum HBsAg Level at Week 8		Baseline; Week 8
Change From Baseline in Serum HBsAg Level at Week 12		Baseline; Week 12
Change From Baseline in Serum HBsAg Level at Week 48		Baseline; Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Boni C, Vecchi A, Rossi M, Laccabue D, Giuberti T, Alfieri A, Lampertico P, Grossi G, Facchetti F, Brunetto MR, Coco B, Cavallone D, Mangia A, Santoro R, Piazzolla V, Lau A, Gaggar A, Subramanian GM, Ferrari C. TLR7 Agonist Increases Responses of Hepatitis B Virus-Specific T Cells and Natural Killer Cells in Patients With Chronic Hepatitis B Treated With Nucleos(T)Ide Analogues. Gastroenterology. 2018 May;154(6):1764-1777.e7. doi: 10.1053/j.gastro.2018.01.030. Epub 2018 Jan 31.
• Janssen HLA, Brunetto MR, Kim YJ, Ferrari C, Massetto B, Nguyen AH, Joshi A, Woo J, Lau AH, Gaggar A, Subramanian GM, Yoshida EM, Ahn SH, Tsai NCS, Fung S, Gane EJ. Safety, efficacy and pharmacodynamics of vesatolimod (GS-9620) in virally suppressed patients with chronic hepatitis B. J Hepatol. 2018 Mar;68(3):431-440. doi: 10.1016/j.jhep.2017.10.027. Epub 2017 Dec 11.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2014
• Primary Completion (ACTUAL): May 11, 2016
• Study Completion (ACTUAL): October 20, 2016

Study Registration Dates

• First Submitted: June 16, 2014
• First Submitted That Met QC Criteria: June 16, 2014
• First Posted (ESTIMATE): June 18, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 14, 2020
• Last Update Submitted That Met QC Criteria: September 22, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Hepatitis B; HBV; GS-9620; TLR-7 Agonist
• 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-283-1059; 2014-001400-22 (EUDRACT_NUMBER); ACTRN12614000628640 (OTHER: ANZCTR)

Drug and device information, study documents

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