A Study of Switching From Entecavir to Tenofovir Disoproxil Fumarate in Subjects With Chronic Hepatitis B

NCT03258710 | Completed Phase 4 Results

• 1 other identifier: 205883
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 18

Brief Summary

Tenofovir Disoproxil Fumarate is a nucleos(t)ide analogue that inhibits Hepatitis B Virus (HBV) growth, and is marketed in Japan with an indication for inhibition of HBV growth in subjects with chronic hepatitis B associated with HBV growth and abnormal liver function. This study has been planned to evaluate the virological effects and safety of switching from ETV to TDF in chronic hepatitis B (hepatitis B e-antigen \[HBeAg\])-positive and HBV- deoxyribonucleic acid (DNA) undetectable subjects. This study is designed as a multi-center, one-arm, post-marketing clinical study to investigate the HBsAg reduction in subjects who have not achieved the long-term goal, the loss of hepatitis B surface antigen (HBsAg). The study will be conducted in HBeAg-positive and HBV-DNA undetectable subjects treated with ETV. After switching ETV to TDF, TDF will be administered for 96 weeks. Approximately 80 subjects will be screened to achieve 65 evaluable subjects.

Conditions

Hepatitis B, Chronic

Keywords

Tenofovir Disoproxil Fumarate; safety; chronic hepatitis B; virological effect

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved 0.25 Logarithm to the Base 10 (Log10) Hepatitis B Surface Antigen (HBsAg) Reduction From the Baseline at Week 48

  Blood samples were collected to evaluate the HBsAg reduction from Baseline at Week 48. HBsAg reduction potential was obtained by evaluating log10 observation values minus log10 Baseline values. The HBsAg responder values were\<=-0.25 log10 and non-responder values were \>-0.25 log10 . Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Full analysis set (FAS) Population is defined as population of all participants enrolled in the study, excluding those who meet either of the following criteria: who have not received any dose of study treatment and who have no efficacy data (HBsAg, HBV-DNA, hepatitis B core-related antigen \[HBcrAg\], HBeAg, hepatitis B surface antibody \[HBsAb\],Hepatitis B envelope antibody \[HBeAb\], alanine aminotransferase \[ALT\]) from at least 15 days after the start of study treatment. Data for HBsAg responders have been presented.

  Baseline (Day 1, Pre-dose) and at Week 48

Secondary Outcomes (35)

• Percentage of Participants Who Achieved 0.25 Log10 HBsAg Reduction From the Baseline at Weeks 24 and 96

  Baseline (Day 1, Pre-dose) and at Weeks 24 and 96

• Percentage of Participants Who Achieved HBsAg Loss at Weeks 24, 48 and 96

  At Weeks 24, 48 and 96

• Percentage of Participants Who Achieved HBsAg/Ab Seroconversion at Weeks 24, 48 and 96

  At Weeks 24, 48 and 96

• Percentage of Participants Who Achieved HBeAg Loss at Weeks 24, 48 and 96

  At Weeks 24, 48 and 96

• Percentage of Participants Who Achieved HBeAg/Ab Seroconversion at Weeks 24, 48 and 96

  At Weeks 24, 48 and 96

Study Arms (1)

All subjects treated with Tenofovir Disoproxil Fumarate

EXPERIMENTAL

Subjects with on-going ETV treatment will be switched to Tenofovir Disoproxil Fumarate treatment. Subjects will start TDF on the day ETV is discontinued, without having overlapping treatment periods. All subjects will receive one tablet of TDF 300 mg once daily orally for 96 weeks.

Drug: Tenofovir Disoproxil Fumarate

Interventions

Tenofovir Disoproxil Fumarate DRUG

Tenofovir Disoproxil Fumarate is a nucleos(t)ide analogue that inhibits HBV growth. All subjects will receive one tablet of TDF 300 mg once daily orally for 96 weeks.

All subjects treated with Tenofovir Disoproxil Fumarate

Eligibility Criteria

• Age: 20 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be 20 to 69 years of age inclusive, at the time of signing the informed consent
• Male and female subjects. A female subject is eligible to participate if she is not pregnant and not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP), OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 days after the last dose of study treatment
• Capable of giving signed informed consent form (ICF)
• Subjects with chronic hepatitis B (CHB) (excluding hospitalized subjects)
• Subjects treated with ETV for at least 2 years prior to initiation of study treatment.
• The serum HBV-DNA level at screening is below the limit of quantitation (\< 2.1 Log10 copies/milliliter \[mL\] or \< 20 international unit \[IU\]/mL).
• Subjects with serum HBeAg positive at screening
• Meet either of the following serum HBsAg levels at screening:
• Serum HBsAg 80 \< to \< 800 IU/mL and fluctuation range is equal or more than -0.1 Log10 IU/mL per year
• Serum HBsAg \>=800 IU/mL
• Meet all of the following criteria at screening:
• Creatinine clearance (CLcr) \>=70 mL/minute. CLcr is calculated using the following Cockcroft-Gault formula.
• Male: CLcr = (body weight in kilogram \[kg\] multiplied by \[140 minus age in years\]) divided by (72 multiplied by serum creatinine \[milligram {mg}/deciliter {dL}\]) Female: CLcr = CLcr (male) multiplied by 0.85

You may not qualify if:

• QTc \> 450 millisecond (msec) or \> 480 msec for subjects with bundle branch block
• Received any interferon or Hepatitis B vaccine therapy within 24 weeks prior to initiation of the study treatment.
• Received overdose of nonsteroidal anti-inflammatory drugs (NSAIDs) (excluding temporary or topical use) within 7 days prior to initiation of the study treatment.
• Received any of the following drugs within 8 weeks prior to initiation of the study treatment (excluding topical products such as ointment and/or cream etc).
• Drugs causing renal impairment (examples: aminoglycosides, amphotericin B, vancomycin, foscarnet, cisplatin, pentamidine, tacrolimus, cyclosporine, some contrast mediums \[ionic high-osmolar contrast media, ionic low-osmolar contrast media\]
• Competitors of renal excretion (except temporary use, example: probenecid)
• Immunosuppressants (examples: azathioprine, cycolphosphamide) or chemotherapeutics (example: etoposide)
• Glucocorticoid preparation
• Received TDF, Adefovir pivoxil (ADV) or Tenofovir Alafenamide Fumarate (TAF) within 2 years prior to initiation of the study treatment
• Participation in another clinical study within 6 months prior to screening, or planned participation in another clinical study simultaneously with this study.
• Co-infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
• Subjects with serious complication other than compensated CHB (cancer, significant renal, cardiovascular, pulmonary, or neurological disease, uncontrollable diabetes, etc.)
• Received or have a plan for solid organ or bone marrow transplantation
• Has proximal tubulopathy.
• Subjects with decompensated CHB who meet the following: direct bilirubin \> 1.5 times upper limit of normal (ULN), Prothrombin Time (PT) \< 60%, platelets \< 75,000/mm3 and serum albumin \< 3.0 g/dL

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (18)

GSK Investigational Site

Aichi, 467-8602, Japan

Location

GSK Investigational Site

Chiba, 270-1694, Japan

Location

GSK Investigational Site

Ehime, 790-0024, Japan

Location

GSK Investigational Site

Ehime, 790-8524, Japan

Location

GSK Investigational Site

Fukuoka, 802-0077, Japan

Location

GSK Investigational Site

Fukuoka, 810-8539, Japan

Location

GSK Investigational Site

Fukuoka, 830-0011, Japan

Location

GSK Investigational Site

Hiroshima, 737-0023, Japan

Location

GSK Investigational Site

Hokkaido, 060-0033, Japan

Location

GSK Investigational Site

Hokkaido, 080-0024, Japan

Location

GSK Investigational Site

Kanagawa, 213-8587, Japan

Location

GSK Investigational Site

Kanagawa, 216-8511, Japan

Location

GSK Investigational Site

Kumamoto, 862-8655, Japan

Location

GSK Investigational Site

Nagasaki, 856-8562, Japan

Location

GSK Investigational Site

Osaka, 545-8586, Japan

Location

GSK Investigational Site

Tokyo, 105-8470, Japan

Location

GSK Investigational Site

Tokyo, 180-8610, Japan

Location

GSK Investigational Site

Tottori, 683-0002, Japan

Location

Related Publications (1)

• Suzuki F, Suzuki Y, Karino Y, Tanaka Y, Kurosaki M, Yatsuhashi H, Atarashi T, Atsukawa M, Watanabe T, Enomoto M, Kudo M, Maeda N, Kohno H, Joko K, Michitaka K, Miki K, Takahashi K, Ide T, Fujiyama S, Kohno T, Itoh H, Tsukamoto S, Suzuki Y, Kawano Y, Sugiura W, Kumada H. Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study. BMC Gastroenterol. 2021 Dec 20;21(1):489. doi: 10.1186/s12876-021-02008-9.

  PMID: 34930140 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

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: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single arm study where on-going ETV treatment is switched to TDF treatment. There is no randomization in this study.

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 23, 2017
• Study Start: October 2, 2017
• Primary Completion: December 28, 2018
• Study Completion: November 25, 2019
• Last Updated: August 4, 2020
• Results First Posted: January 2, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted when justified, for up to another 12 months.

Locations

JP (18)