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

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: Vesatolimod; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02166047

GS-US-283-1059

ACTRN12614000628640 (Other Identifier)

2014-001400-22 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 162 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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162 participants in 12 patient groups, including a placebo group

Placebo 4 Weeks (Cohort A)

Placebo Comparator group

Description:

Placebo tablet once a week for 4 weeks

Treatment:

Drug: Placebo

Vesatolimod 1 mg 4 Weeks (Cohort A)

Experimental group

Description:

Vesatolimod 1 mg tablet once a week for 4 weeks

Treatment:

Drug: Vesatolimod

Vesatolimod 2 mg 4 Weeks (Cohort A)

Experimental group

Description:

Vesatolimod 2 mg tablet once a week for 4 weeks

Treatment:

Drug: Vesatolimod

Vesatolimod 4 mg 4 Weeks (Cohort A)

Experimental group

Description:

Vesatolimod 4 mg tablet once a week for 4 weeks

Treatment:

Drug: Vesatolimod

Placebo 8 Weeks (Cohort B)

Placebo Comparator group

Description:

Placebo tablet once a week for 8 weeks

Treatment:

Drug: Placebo

Vesatolimod 1 mg 8 Weeks (Cohort B)

Experimental group

Description:

Vesatolimod 1 mg tablet once a week for 8 weeks

Treatment:

Drug: Vesatolimod

Vesatolimod 2 mg 8 Weeks (Cohort B)

Experimental group

Description:

Vesatolimod 2 mg tablet once a week for 8 weeks

Treatment:

Drug: Vesatolimod

Vesatolimod 4 mg 8 Weeks (Cohort B)

Experimental group

Description:

Vesatolimod 4 mg tablet once a week for 8 weeks

Treatment:

Drug: Vesatolimod

Placebo 12 Weeks (Cohort C)

Placebo Comparator group

Description:

Placebo tablet once a week for 12 weeks

Treatment:

Drug: Placebo

Vesatolimod 1 mg 12 Weeks (Cohort C)

Experimental group

Description:

Vesatolimod 1 mg tablet once a week for 12 weeks

Treatment:

Drug: Vesatolimod

Vesatolimod 2 mg 12 Weeks (Cohort C)

Experimental group

Description:

Vesatolimod 2 mg tablet once a week for 12 weeks

Treatment:

Drug: Vesatolimod

Vesatolimod 4 mg 12 Weeks (Cohort C)

Experimental group

Description:

Vesatolimod 4 mg tablet once a week for 12 weeks

Treatment:

Drug: Vesatolimod