Clinical trial NCT02166047: Study To Evaluate Safety and Efficacy of Vesatolimod for the Treatment of Chronic Hepatitis B Virus in Virally-Suppressed Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Hepatitis B
HBV
GS-9620
TLR-7 Agonist
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-06-18
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24
timeFrame: Week 24
measure: Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48
timeFrame: Week 48
measure: Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24
timeFrame: Week 24
measure: Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48
timeFrame: Week 48
measure: Change From Baseline in Serum HBsAg Level at Week 4
timeFrame: Baseline; Week 4
measure: Change From Baseline in Serum HBsAg Level at Week 8
timeFrame: Baseline; Week 8
measure: Change From Baseline in Serum HBsAg Level at Week 12
timeFrame: Baseline; Week 12
measure: Change From Baseline in Serum HBsAg Level at Week 48
timeFrame: Baseline; Week 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Jose
country: United States
state: California
city: Honolulu
country: United States
state: Hawaii
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Flushing
country: United States
state: New York
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: San Giovanni Rotondo
country: Italy
state: FG
city: Milan
country: Italy
city: Parma
country: Italy
city: Pisa
country: Italy
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Rotterdam
country: Netherlands
city: Auckland
country: New Zealand
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
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 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.