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

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02166047
• Other study ID #: GS-US-283-1059
• Secondary ID: 2014-001400-22AC
• Status: Completed
• Phase: Phase 2
• Start date: June 30, 2014
• Est. completion date: October 20, 2016

Study information

• Verified date: September 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: October 20, 2016
• Est. primary completion date: May 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Vesatolimod
Vesatolimod tablet administered orally
• Placebo
Placebo to match vesatolimod tablet administered orally

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Korea, Republic of,  Netherlands,  New Zealand, 

References & Publications (2)

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 Hepatiti — View Citation

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 patie — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change From Baseline in Serum HBsAg Level at Week 4		Baseline; Week 4
Secondary	Change From Baseline in Serum HBsAg Level at Week 8		Baseline; Week 8
Secondary	Change From Baseline in Serum HBsAg Level at Week 12		Baseline; Week 12
Secondary	Change From Baseline in Serum HBsAg Level at Week 48		Baseline; Week 48