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Trial record 43 of 309 for:    hepatitis b | Recruiting, Not yet recruiting, Available Studies

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

This study is currently recruiting participants.
Verified October 2017 by GlaxoSmithKline
Sponsor:
ClinicalTrials.gov Identifier:
NCT03258710
First Posted: August 23, 2017
Last Update Posted: October 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
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.

Condition Intervention Phase
Hepatitis B, Chronic Drug: Tenofovir Disoproxil Fumarate Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
This is a single arm study where on-going ETV treatment is switched to TDF treatment. There is no randomization in this study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-centre, One-arm Prospective Study to Evaluate Efficacy and Safety of Switching From Entecavir (ETV) to Tenofovir Disoproxil Fumarate (TDF) in Japanese Chronic Hepatitis B HBeAg-positive and HBV-DNA Undetectable Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Proportion of subjects achieving 0.25 Log10 HBsAg reduction from the Baseline at Week 48 [ Time Frame: Baseline and at Week 48 ]
    Blood samples will be collected at Baseline and Week 48 to evaluate the HBsAg reduction potential at Week 48.


Secondary Outcome Measures:
  • Proportion of subjects achieving 0.25 Log10 HBsAg reduction from the Baseline at Weeks 24 and 96 [ Time Frame: Baseline and Weeks 24 and 96 ]
    Blood samples will be collected at Baseline and at Weeks 24 and 96 to evaluate the virological effects.

  • Proportion of subjects achieving HBsAg loss at Weeks 24, 48 and 96 [ Time Frame: Baseline and Weeks 24, 48 and 96 ]
    Blood samples will be collected at Baseline and at Weeks 24, 48 and 96 to evaluate the virological effects.

  • Proportion of subjects achieving HBsAg/Ab seroconversion at Weeks 24, 48 and 96 [ Time Frame: Baseline and Weeks 24, 48 and 96 ]
    Blood samples will be collected at Baseline and at Weeks 24, 48 and 96 to evaluate the virological effects.

  • Proportion of subjects achieving HBeAg loss at Weeks 24, 48 and 96 [ Time Frame: Baseline and Weeks 24, 48 and 96 ]
    Blood samples will be collected at Baseline and at Weeks 24, 48 and 96 to evaluate the virological effects.

  • Proportion of subjects achieving HBeAg/Ab seroconversion at Weeks 24, 48 and 96 [ Time Frame: Baseline and Weeks 24, 48 and 96 ]
    Blood samples will be collected at Baseline and at Weeks 24, 48 and 96 to evaluate the virological effects.

  • Reduction of HBsAg titer from the Baseline at Weeks 24, 48 and 96 [ Time Frame: Baseline and Weeks 24, 48 and 96 ]
    Blood samples will be collected at Baseline and at Weeks 24, 48 and 96 to evaluate the virological effects.

  • Reduction of Hepatitis B core-related antigen (HBcrAg) titer from the Baseline at Weeks 24, 48 and 96 [ Time Frame: Baseline and Weeks 24, 48 and 96 ]
    Blood samples will be collected at Baseline and at Weeks 24, 48 and 96 to evaluate the virological effects.

  • Number of subjects with adverse events (AEs), serious AEs (SAEs) [ Time Frame: Up to Week 96 ]
    An AE is any untoward medical occurrence in a subject, temporarily associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward medical occurrence, that results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment, or events meeting liver chemistry stopping criteria, will be categorized as SAE.

  • Number of subjects with abnormal findings in hematology [ Time Frame: Up to Week 96 ]
    Hematology parameters will be evaluated.

  • Number of subjects with abnormal findings in clinical chemistry [ Time Frame: Up to Week 96 ]
    Clinical chemistry parameters will be evaluated.

  • Number of subjects with abnormal findings in urinalysis [ Time Frame: Up to Week 96 ]
    Urinalysis parameters will be evaluated.

  • Number of subjects with abnormal findings in systolic and diastolic blood pressure [ Time Frame: Up to Week 96 ]
    Systolic and diastolic blood pressure will be evaluated as a measure of safety. It will be preceded by at least 5 minutes of rest for the subject in a quiet setting without distractions.

  • Number of subjects with abnormal findings in pulse rate [ Time Frame: Up to Week 96 ]
    Pulse rate will be evaluated as a measure of safety. It will be preceded by at least 5 minutes of rest for the subject in a quiet setting without distractions.

  • Number of subjects with abnormal findings in body temperature [ Time Frame: Up to Week 96 ]
    Axillary temperature will be evaluated as a measure of safety.

  • Number of subjects with abnormal findings in 12-lead electrocardiogram (ECG) [ Time Frame: Up to Week 96 ]
    12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) interval.

  • Number of subjects with abnormal findings in bone densitometry [ Time Frame: Up to Week 96 ]
    Bone densitometry will be performed on either lumbar spine or femur, using dual-energy X-ray absorptiometry (DEXA). In case of difficulty to perform with DEXA or on either lumbar spine or femur, other region (radius or calcaneus) or other method will be selected.


Estimated Enrollment: 65
Actual Study Start Date: September 29, 2017
Estimated Study Completion Date: November 30, 2019
Estimated Primary Completion Date: November 30, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All subjects treated with Tenofovir Disoproxil Fumarate
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
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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

  • Hemoglobin >= 8 gram/dL
  • WBC >=1000 per cubic millimeter (mm^3)

Exclusion Criteria:

  • 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
  • Autoimmune hepatitis (Antinuclear titer > 1:160), excluding CHB
  • Subjects with or suspected of having hepatocellular carcinoma (HCC) (including both primary and metastatic) from diagnostic imaging at screening, or with serum alpha-fetoprotein (AFP) > 50 nanogram (ng)/mL at screening
  • History of HCC (except subjects who underwent resection or received curative treatment by radiofrequency, and with AFP <=10 ng/mL at screening)
  • Woman who is pregnant, possibly pregnant, lactating or planning a pregnancy during the study period.
  • Psychiatry disorder or cognitive disorder that may affect the subject's ability to give informed consent or to follow specified study procedures.
  • Subjects with a history of alcohol or drug abuse
  • Subjects whom the investigator (or sub-investigator) considers ineligible for the study.
  • Subjects with hypersensitivity to study treatments or their components, nucleoside and/or nucleotide analogues. Subjects with drug allergy that, in the investigator's (sub-investigator's) [or medical monitor's] opinion, labeled contraindication for participation in the study, or other allergy.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03258710


Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
Japan
GSK Investigational Site Not yet recruiting
Aichi, Japan, 467-8602
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Ehime, Japan, 790-0024
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Ehime, Japan, 790-8524
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Hiroshima, Japan, 737-0023
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Hokkaido, Japan, 060-0033
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Hokkaido, Japan, 080-0016
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Kanagawa, Japan, 213-8587
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Nagasaki, Japan, 856-8562
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Osaka, Japan, 545-8586
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Not yet recruiting
Osaka, Japan, 589-8511
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Tokyo, Japan, 105-8470
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Tokyo, Japan, 180-8610
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Tottori, Japan, 683-0002
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03258710     History of Changes
Other Study ID Numbers: 205883
First Submitted: August 21, 2017
First Posted: August 23, 2017
Last Update Posted: October 18, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Tenofovir Disoproxil Fumarate
safety
chronic hepatitis B
virological effect

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Entecavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents