Study to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed

NCT02979613 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-320-40182016-003632-20
• Study Type: interventional
• Target: 490
• Locations: 8 countries
• Sites: 39

Brief Summary

The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching to tenofovir alafenamide (TAF) versus continuing tenofovir disoproxil fumarate (TDF) in virologically suppressed adults with chronic hepatitis B virus (HBV) infection.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm

  The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who: 1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or 2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and * Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or * Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL

  Week 48

Secondary Outcomes (25)

• Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm

  Week 96

• Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48

  Weeks 48

• Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48

  Week 48

• Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96

  Week 96

• Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96

  Week 96

Study Arms (2)

TAF 25 mg

EXPERIMENTAL

Double-blind (DB) phase: TAF 25 mg + TDF placebo for up to 53 weeks. Open-label extension (OLE) phase: TAF 25 mg for up to 52 weeks.

Drug: TAF; Drug: TDF Placebo

TDF 300 mg

ACTIVE COMPARATOR

DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.

Drug: TAF; Drug: TDF; Drug: TAF Placebo

Interventions

TAF DRUG

25 mg tablet administered orally once daily

Also known as: Vemlidy®, GS-7340

TAF 25 mg; TDF 300 mg

TDF DRUG

300 mg tablet administered orally once daily

Also known as: Viread®

TDF 300 mg

TAF Placebo DRUG

Tablet administered orally once daily

TDF 300 mg

TDF Placebo DRUG

Tablet administered orally once daily

TAF 25 mg

Eligibility Criteria

• Age: 18 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
• Adult male and non-pregnant, non-lactating females
• Documented evidence of chronic hepatitis B virus (HBV) infection previously
• Maintained on tenofovir disoproxil fumarate (TDF) 300 mg once daily for at least 48 weeks, and as monotherapy for chronic hepatitis B for at least 24 weeks with viral suppression (HBV DNA \< lower limit of quantitation) for a minimum of 12 weeks prior to screening
• Adequate renal function
• Normal Electrocardiogram

You may not qualify if:

• Pregnant women or women who are breastfeeding
• Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study.
• Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or human immunodeficiency virus (HIV)
• Evidence of hepatocellular carcinoma
• Current evidence of, or recent (≤ 5 year) history of clinical hepatic decompensation
• Abnormal hematological and biochemical parameters, including:
• Hemoglobin \< 10 g/dL
• Absolute neutrophil count \< 750/mm\^3
• Platelets ≤ 50,000/mm\^3
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 × upper limit of the normal (ULN)
• Albumin \< 3.0 mg/ dL
• International normalized ratio (INR) \> 1.5 × ULN (unless stable on anticoagulant regimen)
• Total bilirubin \> 2.5 × ULN
• Received solid organ or bone marrow transplant
• Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (eg, basal cell skin cancer). Individuals under evaluation for possible malignancy are not eligible.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (39)

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Los Angeles, California, United States

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Palo Alto, California, United States

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Pasadena, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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San Jose, California, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Novi, Michigan, United States

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Flushing, New York, 11355, United States

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Flushing, New York, United States

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New York, New York, 10029, United States

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New York, New York, United States

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Philadelphia, Pennsylvania, 19107, United States

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Philadelphia, Pennsylvania, United States

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Nashville, Tennessee, United States

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Sugar Land, Texas, 77478, United States

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Edmonton, Canada

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Toronto, Canada

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Vancouver, Canada

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Hong Kong, Hong Kong

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Kowloon, Hong Kong

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Milan, 20122, Italy

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Goyang, Gyeonggi-d, South Korea

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Daegu, 700-721, South Korea

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Seoul, 03722, South Korea

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Seoul, 03830, South Korea

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Seoul, 05505, South Korea

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Seoul, 06973, South Korea

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Seoul, 135-710, South Korea

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Seoul, 152-703, South Korea

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Seoul, South Korea

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Barcelona, Spain

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Majadahonda, Spain

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Chiayi City, 60002, Taiwan

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Kaohsiung City, Taiwan

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Taipei, 10002, Taiwan

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London, E1 1BB, United Kingdom

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London, United Kingdom

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Related Publications (1)

• Lampertico P, Buti M, Fung S, Ahn SH, Chuang WL, Tak WY, Ramji A, Chen CY, Tam E, Bae H, Ma X, Flaherty JF, Gaggar A, Lau A, Liu Y, Wu G, Suri V, Tan SK, Subramanian GM, Trinh H, Yoon SK, Agarwal K, Lim YS, Chan HLY. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patients with chronic hepatitis B: a randomised, double-blind, phase 3, multicentre non-inferiority study. Lancet Gastroenterol Hepatol. 2020 May;5(5):441-453. doi: 10.1016/S2468-1253(19)30421-2. Epub 2020 Feb 20.

  PMID: 32087795 RESULT

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide; Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis B; 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

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 1, 2016
• Study Start: December 29, 2016
• Primary Completion: September 10, 2018
• Study Completion: January 30, 2020
• Last Updated: September 14, 2020
• Results First Posted: September 25, 2019

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (17); KR (9); HK (2); CA (3); TW (3); GB (2); IT (1); ES (2)