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

NCT02166047 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: GS-US-283-10592014-001400-22ACTRN12614000628640
• Study Type: interventional
• Target: 162
• Locations: 6 countries
• Sites: 23

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

Keywords

Hepatitis B; HBV; GS-9620; TLR-7 Agonist

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24

  Week 24

• Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48

  Week 48

• Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24

  Week 24

• Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48

  Week 48

• Change From Baseline in Serum HBsAg Level at Week 4

  Baseline; Week 4

Study Arms (12)

Placebo 4 Weeks (Cohort A)

PLACEBO COMPARATOR

Placebo tablet once a week for 4 weeks

Drug: Placebo

Vesatolimod 1 mg 4 Weeks (Cohort A)

EXPERIMENTAL

Vesatolimod 1 mg tablet once a week for 4 weeks

Drug: Vesatolimod

Vesatolimod 2 mg 4 Weeks (Cohort A)

EXPERIMENTAL

Vesatolimod 2 mg tablet once a week for 4 weeks

Drug: Vesatolimod

Vesatolimod 4 mg 4 Weeks (Cohort A)

EXPERIMENTAL

Vesatolimod 4 mg tablet once a week for 4 weeks

Drug: Vesatolimod

Placebo 8 Weeks (Cohort B)

PLACEBO COMPARATOR

Placebo tablet once a week for 8 weeks

Drug: Placebo

Vesatolimod 1 mg 8 Weeks (Cohort B)

EXPERIMENTAL

Vesatolimod 1 mg tablet once a week for 8 weeks

Drug: Vesatolimod

Vesatolimod 2 mg 8 Weeks (Cohort B)

EXPERIMENTAL

Vesatolimod 2 mg tablet once a week for 8 weeks

Drug: Vesatolimod

Vesatolimod 4 mg 8 Weeks (Cohort B)

EXPERIMENTAL

Vesatolimod 4 mg tablet once a week for 8 weeks

Drug: Vesatolimod

Placebo 12 Weeks (Cohort C)

PLACEBO COMPARATOR

Placebo tablet once a week for 12 weeks

Drug: Placebo

Vesatolimod 1 mg 12 Weeks (Cohort C)

EXPERIMENTAL

Vesatolimod 1 mg tablet once a week for 12 weeks

Drug: Vesatolimod

Vesatolimod 2 mg 12 Weeks (Cohort C)

EXPERIMENTAL

Vesatolimod 2 mg tablet once a week for 12 weeks

Drug: Vesatolimod

Vesatolimod 4 mg 12 Weeks (Cohort C)

EXPERIMENTAL

Vesatolimod 4 mg tablet once a week for 12 weeks

Drug: Vesatolimod

Interventions

Vesatolimod DRUG

Vesatolimod tablet administered orally

Also known as: GS-9620

Vesatolimod 1 mg 12 Weeks (Cohort C); Vesatolimod 1 mg 4 Weeks (Cohort A); Vesatolimod 1 mg 8 Weeks (Cohort B); Vesatolimod 2 mg 12 Weeks (Cohort C); Vesatolimod 2 mg 4 Weeks (Cohort A); Vesatolimod 2 mg 8 Weeks (Cohort B); Vesatolimod 4 mg 12 Weeks (Cohort C); Vesatolimod 4 mg 4 Weeks (Cohort A); Vesatolimod 4 mg 8 Weeks (Cohort B)

Placebo DRUG

Placebo to match vesatolimod tablet administered orally

Placebo 12 Weeks (Cohort C); Placebo 4 Weeks (Cohort A); Placebo 8 Weeks (Cohort B)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (23)

Unknown Facility

Los Angeles, California, 90095, United States

Location

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San Diego, California, 92154, United States

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San Francisco, California, 94118, United States

Location

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San Jose, California, 95128, United States

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Honolulu, Hawaii, 96734, United States

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Boston, Massachusetts, 02111, United States

Location

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Boston, Massachusetts, 02215, United States

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Detroit, Michigan, 48202, United States

Location

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Flushing, New York, 11355, United States

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Vancouver, British Columbia, V5Z 1M9, Canada

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Winnipeg, Manitoba, R3E 3P4, Canada

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Toronto, Ontario, M5G2C4, Canada

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Toronto, Ontario, M5T 2S8, Canada

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San Giovanni Rotondo, FG, 71013, Italy

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Milan, 20122, Italy

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Parma, 43126, Italy

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Pisa, 56124, Italy

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Rotterdam, 3015 CE, Netherlands

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Auckland, 1142, New Zealand

Location

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Seoul, 110-744, South Korea

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Seoul, 120-752, South Korea

Location

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Seoul, 135-710, South Korea

Location

Unknown Facility

Seoul, 138-736, South Korea

Location

Related 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 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.

  PMID: 29378197 RESULT

• 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.

  PMID: 29104121 RESULT

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

vesatolimod

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2014
• First Posted: June 18, 2014
• Study Start: June 30, 2014
• Primary Completion: May 11, 2016
• Study Completion: October 20, 2016
• Last Updated: October 14, 2020
• Results First Posted: September 2, 2020

Record last verified: 2020-09

Locations

KR (4); CA (4); US (9); NL (1); IT (4); NZ (1)