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

NCT ID: NCT02166047

Last Updated: 2020-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2016-10-20

Brief Summary

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).

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo 4 Weeks (Cohort A)

Placebo tablet once a week for 4 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to match vesatolimod tablet administered orally

Vesatolimod 1 mg 4 Weeks (Cohort A)

Vesatolimod 1 mg tablet once a week for 4 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Vesatolimod 2 mg 4 Weeks (Cohort A)

Vesatolimod 2 mg tablet once a week for 4 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Vesatolimod 4 mg 4 Weeks (Cohort A)

Vesatolimod 4 mg tablet once a week for 4 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Placebo 8 Weeks (Cohort B)

Placebo tablet once a week for 8 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to match vesatolimod tablet administered orally

Vesatolimod 1 mg 8 Weeks (Cohort B)

Vesatolimod 1 mg tablet once a week for 8 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Vesatolimod 2 mg 8 Weeks (Cohort B)

Vesatolimod 2 mg tablet once a week for 8 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Vesatolimod 4 mg 8 Weeks (Cohort B)

Vesatolimod 4 mg tablet once a week for 8 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Placebo 12 Weeks (Cohort C)

Placebo tablet once a week for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to match vesatolimod tablet administered orally

Vesatolimod 1 mg 12 Weeks (Cohort C)

Vesatolimod 1 mg tablet once a week for 12 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Vesatolimod 2 mg 12 Weeks (Cohort C)

Vesatolimod 2 mg tablet once a week for 12 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Vesatolimod 4 mg 12 Weeks (Cohort C)

Vesatolimod 4 mg tablet once a week for 12 weeks

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Vesatolimod tablet administered orally

Interventions

Vesatolimod

Vesatolimod tablet administered orally

Intervention Type: DRUG

Placebo

Placebo to match vesatolimod tablet administered orally

Intervention Type: DRUG

Other Intervention Names

GS-9620

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Los Angeles, California, United States

San Diego, California, United States

San Francisco, California, United States

San Jose, California, United States

Honolulu, Hawaii, United States

Boston, Massachusetts, United States

Boston, Massachusetts, United States

Detroit, Michigan, United States

Flushing, New York, United States

Vancouver, British Columbia, Canada

Winnipeg, Manitoba, Canada

Toronto, Ontario, Canada

Toronto, Ontario, Canada

San Giovanni Rotondo, FG, Italy

Milan, , Italy

Parma, , Italy

Pisa, , Italy

Rotterdam, , Netherlands

Auckland, , New Zealand

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Countries

United States; Canada; Italy; Netherlands; New Zealand; South Korea

References

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.

Reference Type: RESULT

PMID: 29378197 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29104121 (View on PubMed)

Other Identifiers

2014-001400-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACTRN12614000628640

Identifier Type: OTHER

Identifier Source: secondary_id

GS-US-283-1059

Identifier Type: -

Identifier Source: org_study_id