Hepatitis B, ChronicPhase 4NCT02195518
Tenofovir Disoproxil Fumarate (TDF) 300mg 3 Years RD Therapy Chinese Chronic Hepatitis B (CHN) CHB Multiple Nucleos(t)Ide Analogues (NAs) Failure Points Pts PH4 PMS Study
A Phase 4 study testing Tenofovir disoproxil fumarate in people with Hepatitis B, Chronic, run by GlaxoSmithKline at 12 sites in China.
Trial summary
This is a phase IV, single-arm, open-label, multi-centre study to assess the efficacy of TDF in Chronic hepatitis B (CHB) subjects following failure of multiple Nucleos(t)ide analogues (NAs). The study will enrol 200 CHB subjects following failure of multiple NAs. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Tenofovir disoproxil fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 213 participants
- Where
- 12 sitesChina
- Study dates
- 18 Mar 2015to 14 Aug 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged between 18-65years (inclusive). Male or female; a female is eligible to enter and participate in this study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
- Child-bearing potential, has a negative serum pregnancy test at baseline, and agrees to one of the following methods for avoidance of pregnancy during the period of the study and until 30 days after last dose of study medication: Oral contraceptive, either combined or progestogen alone, Injectable progestogen, Implants of levonorgestrel, Oestrogenic vaginal ring, Percutaneous contraceptive patches., Intrauterine device (IUD) or intrauterine system (IUS) showing that the expected failure rate is less than 1% per year as stated in the IUD or IUS product label, Has a male partner who is sterilised, Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film /cream/suppository).
- The ability to understand and sign a written informed consent prior to any study-related procedure and comply with the requirements of the study.
- Positive HBsAg for more than 6 months, and anti-HBs negative.
- Serum HBV DNA level >=200 IU/mL at study screening (Use central lab results).
- Experienced multiple NAs treatment failure which is defined as HBV DNA greater than 200 IU/mL after at least two NAs treatment (at least 6 months continuous treatment for each NA(s), total duration is no less than 12 months). In addition, subjects judged by the treating physician to have adhered to previous NA therapy.
- Agreement not to participate in any other investigational trials or to undertake other HBV systemic antiviral or interferon (IFN) regimens during participation in this study.
Who cannot join
- Hepatocellular carcinoma as evidenced by one of the following: Suspicious foci on ultrasound or radiological examination, Normal ultrasound but a history of rising serum alpha-fetoprotein and serum alpha-fetoprotein >20 nanogram (ng) per mL at screening.
- Clinical signs of decompensated liver disease at baseline. These may include but are not limited to:Total serum bilirubin >1.5 x Upper limit of the normal range (ULN), International Normalized Ratio >1.3, Serum albumin <32grams per Liter (g/L), History of clinical hepatic decompensation (e.g., ascites, variceal bleeding, or encephalopathy).
- Creatinine clearance less than 70 milliliter per minutes (mL/min).
- Alanine aminotransferase >10 times ULN at screening or history of acute exacerbation leading to transient decompensation.
- Haemoglobin <8 grams per deciliter (g/dL), absolute neutrophil count <1.0 x 10^9 per Liter, platelets <75 x 10^9 per Liter.
- Documented co-infection with hepatitis A (HAV), hepatitis C (HCV), hepatitis delta virus (HDV), hepatitis E virus (HEV) or Human immunodeficiency virus (HIV). For HCV co-infection, subjects who are anti-HCV positive and in whom HCV RNA is undetectable are considered to be not eligible for enrolment.
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- Evidence of active liver disease due to autoimmune hepatitis (antinuclear antibody titre >1:160)
- Any serious or active medical or psychiatric illnesses other than hepatitis B which, in the opinion of the Investigator, would interfere with subject treatment, assessment or compliance with the protocol. This would include any uncontrolled clinically significant renal, cardiac, pulmonary, vascular, neurogenic, digestive, metabolic (diabetes, thyroid disorders, adrenal disease), immunodeficiency disorders, pathological fractures or cancer.
- Active alcohol or drug abuse or history of alcohol or drug abuse considered by the Investigator to be sufficient to hinder compliance with treatment, participation in the study or interpretation of results.
- A female who is breastfeeding or plan to breast.
- Use of immunosuppressive therapy, immunomodulatory therapy [including Pegylated interferon (PEG-IFN) and short-acting interferon or thymosin alpha], systemic cytotoxic agents within the previous 6 months prior to screening.
- Planned for liver transplantation or previous liver transplantation.
- Receipt of TDF within 6 months prior to screening.
- Therapy with nephrotoxic drugs (e.g., aminoglycosides, amphotercin B, vancomycin, cidofovir, foscarnet, cis-platinum, pentamidine etc.) or competitors of renal excretion (e.g., probenecid) within 2 months prior to study screening or the expectation that subject will receive any of these during the course of the study.
- History of hypersensitivity to nucleoside and/or nucleotide analogues and/or any component of study medication.
- Inability to comply with study requirements as determined by the study Investigator.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
China12 sites
GSK Investigational Site
Beijing, 100034
GSK Investigational Site
Beijing, 100044
GSK Investigational Site
Beijing, 100050
GSK Investigational Site
Beijing, 100054
GSK Investigational Site
Changchun, Jilin
GSK Investigational Site
Chengdu, Sichuan, 610041
GSK Investigational Site
Guangzhou, Guangdong, 510060
GSK Investigational Site
Guangzhou, Guangdong, 510150
GSK Investigational Site
Hangzhou, Zhejiang, 310000
GSK Investigational Site
Shanghai, 200025
GSK Investigational Site
Shanghai, 200040
GSK Investigational Site
Zhengzhou
About this study
Official title: A Multi-centre, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of Tenofovir Disoproxil Fumarate(TDF) Treatment in Chinese Chronic Hepatitis B (CHB) Subjects Following Failure of Multiple Nucleos(t)Ide Analogues(NAs)
This is a phase IV, single-arm, open-label, multi-centre study to assess the efficacy of TDF in Chronic hepatitis B (CHB) subjects following failure of multiple Nucleos(t)ide analogues (NAs). The study will enrol 200 CHB subjects following failure of multiple NAs. Subjects will be assessed for eligibility at a screening visit, with eligible subjects returning for a baseline assessment after approximately 4 weeks (Screening phase). In the treatment phase all enrolled subjects will receive open label TDF at a dose of 300 milligrams (mg) orally once daily. All the eligible study subjects will undergo safety and efficacy assessments every 12 weeks for a total of 14 visits. Tenofovir disoproxil fumarate, the oral pro-drug of tenofovir (TFV), is a nucleotide analogue that inhibits viral polymerases by direct binding and after incorporation into deoxyribonucleic acid (DNA), by termination of the DNA) chain. TDF is a highly potent treatment in treatment-naïve and lamivudine (LAM) resistant CHB patients. The purpose of our study is to evaluate the efficacy of TDF treatment in Chinese CHB patients following failure of multiple NAs. In addition, the study will also explore the relationship of baseline factors and early HBV DNA suppression to long-term virological response. The efficacy of TDF in multi-drug resistant patients will be analysed separately. The data generated by this study could then be used to optimize the clinical application of TDF and provide new evidence for management of the HBV infections following failure of multiple NAs. The result of this study will help Chinese physicians better manage the CHB patients following failure of multiple NAs.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Tenofovir disoproxil fumarate
- Keywords
- Chronic Hepatitis B, Tenofovir disoproxil fumarate, Failure of multiple NAs treatment
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir disoproxil fumarateDrug
Tenofovir disoproxil fumarate tablets supplied will be white, almond-shaped, film-coated tablets containing 300 mg of TDF. Each tablet contains the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, pregelatinised starch, croscarmellose sodium, and magnesium stearate.
| Study group | Role | What they receive |
|---|---|---|
| Tenofovir Disoproxil Fumarate | Experimental | All enrolled subjects will receive open label TDF at a dose of 300 milligram (mg) orally once daily during the study period. Receives: Drug: Tenofovir disoproxil fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <20 International Unit Per Milliliter (IU/mL) at Week 144
HBV DNA level were analyzed using the sensitive HBV test in central laboratory using Roche cobas Taqman HBV test from the blood samples collected at Week 144. A 95 percent confidence interval (CI) was constructed by normal approximation and continuity correction method. Percentage of participants with serum HBV DNA <20 IU/mL at Week 144 have been presented. The Modified Intent-to-treat (mITT) Population was defined as all recruited participants who received at least one dose of study medication.
Measured: At Week 144
Secondary outcomes (17)
Percentage of Participants With Serum HBV DNA <20 IU/mL and Serum HBV DNA <69 IU/mL at Weeks 48 and 96
HBV DNA level were analyzed using the sensitive HBV test in central laboratory using Roche cobas Taqman HBV test from the blood samples collected at Weeks 48 and 96. Virological response was assessed by proportion of participants with serum serum HBV <20 IU/mL and <69 IU/mL at Weeks 48 and 96. Percentage of participants with serum HBV DNA <20 IU/mL and <69 IU/mL at Weeks 48 and 96 have been presented.
Measured: At Weeks 48 and 96
Percentage of Participants in the Subgroup With Confirmed Multi-drug Resistance Mutations at Baseline With Serum HBV DNA <20 IU/mL and Serum HBV DNA <69 IU/mL at Weeks 48, 96 and 144
Serum samples were collected and analyzed for HBV DNA levels at indicated time points. Resistance surveillance of the HBV polymerase gene were performed by direct sequencing for all participants at Baseline. Day 0 was considered as Baseline. Percentage of participants in the subgroup with confirmed multi-drug resistance mutations at Baseline with serum HBV DNA <20 IU/mL and serum HBV DNA <69 IU/mL at Weeks 48, 96 and 144 have been presented.
Measured: At Weeks 48, 96, and 144
Change From Baseline in Logarithm to the Base 10 (Log 10) Reduction in Serum HBV DNA at Week 48, 96 and 144
Log10 reduction in serum HBV DNA was analyzed by patterns of mutation. The patterns of mutation were summarized by 2 categories. Category 1 included wild-type, LAM-R (Lamivudine-resistant), ADV-R (Adefovir-resistant) and ETV-R (Entecavir-resistant). Category 2 included Wild type, ADV-R single mutation, ADV-R double mutation and other mutation. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks 48,96, and 144
Percentage of Hepatitis B e Antigen (HBeAg) Positive Participants Achieving HBeAg Loss, HBeAg Seroconversion or Hepatitis B s Antigen (HBsAg) Loss and HBsAg Seroconversion at Weeks 48, 96, and 144
Serological response was assessed at Weeks 48, 96 and 144 in participants with Positive HBeAg at Baseline (Day 0). It was presented as HBeAg Loss, HBeAg Seroconversion, HBsAg Loss and HBsAg Seroconversion. HBeAg Loss was defined as HBeAg changed to be negative. HBeAg seroconversion was defined as HBeAg changed to negative and HBeAb was positive. HBsAg Loss was defined as HBsAg changed to be negative. HBsAg seroconversion was defined as HBsAg changed to negative and HBsAb was positive.
Measured: At Weeks 48, 96 and 144
Percentage of HBeAg Negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Weeks 48, 96, and 144
Serological response was assessed at Weeks 48, 96 and 144 in participants with negative HBeAg at Baseline (Day 0). HBsAg Loss was defined as HBsAg changed to be negative. HBsAg seroconversion was defined as HBsAg changed to negative and HBsAb was positive.
Measured: At Weeks 48,96, and 144
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48, 96, and 144 in Participants Who Had Abnormal ALT at Baseline
Blood samples were collected for evaluation of ALT at indicated time points. ALT normalization was defined as measurement less than or equal to the upper limit of the normal range. Normal range for ALT is 7 to 56 International Units per liter. Percentage of participants with ALT normalization at Weeks 48, 96, and 144 in Participants who had abnormal ALT at Baseline (Day 0) have been presented.
Measured: At Weeks 48, 96, and 144
Percentage of Participants Who Experienced Viral Breakthrough up to Week 144
Viral breakthrough was defined as 1 log increase in HBV DNA from nadir determined by two sequential HBV DNA measurements. Percentage of participants who experienced viral breakthrough at Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144 have been presented.
Measured: At Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120,132, and 144
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs
An adverse event was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is defined as AE occurred on or after the first dose date of study drug, SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement or events associated with liver injury and impaired liver function. The Safety analysis (SA) Population was defined as all participants who received at least one dose of study medication and have at least one post Baseline safety assessment.
Measured: Up to Week 144
Change From Baseline in Hematology Parameters: White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets
Blood samples were collected to analyze the hematology parameters: WBC, basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelets. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks 24, 48, 72, 96, 120 and 144
Change From Baseline in Hemoglobin (Hb)
Blood samples were collected to analyze Hb values. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks 24, 48, 72, 96, 120 and 144
Change From Baseline in Red Blood Cells (RBC)
Blood samples were collected to analyze RBC values. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks 24, 48, 72, 96, 120 and 144
Change From Baseline in Chemistry Parameters: ALT, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-Glutamyltransferase (GGT), Creatinine Phosphokinase (CK), Lactose Dehydrogenase (LDH)
Blood samples were collected to analyze the chemistry parameters: ALT, ALP, AST, GGT, CK, LDH. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameters: Total Billirubin, Direct Bilirubin, Serum Creatinine
Blood samples were collected to analyze the chemistry parameters: total billirubin,direct bilirubin and serum creatinine. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameters: Albumin, Total Protein
Blood samples were collected to analyze the chemistry parameters: albumin and total protein. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameter: Blood Urea Nitrogen (BUN), Potassium, Sodium, Chloridian, Phosphorus, Calcium and Fasting Blood Glucose.
Blood samples were collected to analyze the chemistry parameters: BUN, potassium, sodium, chloridian, phosphorus, calcium and fasting blood glucose. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameter: Creatinine Clearance Rate
Blood samples were collected to analyze the chemistry parameter: creatinine clearance rate. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate (eGFR)
Blood samples were collected to analyze the chemistry parameter: eGFR. Day 0 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2014 (estimated)
- Study start18 Mar 2015
- Primary completion14 Aug 2018
- Study completion14 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02195518
- Sponsor's protocol ID
- 201215
- Status last verified
- Oct 2019
- First submitted
- 17 Jul 2014
- Last updated
- 4 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of Tenofovir Disoproxil Fumarate(TDF) Treatment in Chinese Chronic Hepatitis B (CHB) Subjects Following Failure of Multiple Nucleos(t)Ide Analogues(NAs)
- ClinicalTrials.gov ID
- NCT02195518
- Acronym / sponsor ID
- 201215
- Conditions
- Hepatitis B, Chronic
- Keywords
- Chronic Hepatitis B, Tenofovir disoproxil fumarate, Failure of multiple NAs treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 213 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 18 Mar 2015 (actual)
- Primary completion
- 14 Aug 2018 (actual)
- Study completion
- 14 Aug 2018 (actual)
- First posted
- 21 Jul 2014 (estimated)
- Results
- Posted 4 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase IV, single-arm, open-label, multi-centre study to assess the efficacy of TDF in Chronic hepatitis B (CHB) subjects following failure of multiple Nucleos(t)ide analogues (NAs). The study will enrol 200 CHB subjects following failure of multiple NAs. Subjects will be assessed for eligibility at a screening visit, with eligible subjects returning for a baseline assessment after approximately 4 weeks (Screening phase). In the treatment phase all enrolled subjects will receive open label TDF at a dose of 300 milligrams (mg) orally once daily. All the eligible study subjects will undergo safety and efficacy assessments every 12 weeks for a total of 14 visits. Tenofovir disoproxil fumarate, the oral pro-drug of tenofovir (TFV), is a nucleotide analogue that inhibits viral polymerases by direct binding and after incorporation into deoxyribonucleic acid (DNA), by termination of the DNA) chain. TDF is a highly potent treatment in treatment-naïve and lamivudine (LAM) resistant CHB patients. The purpose of our study is to evaluate the efficacy of TDF treatment in Chinese CHB patients following failure of multiple NAs. In addition, the study will also explore the relationship of baseline factors and early HBV DNA suppression to long-term virological response. The efficacy of TDF in multi-drug resistant patients will be analysed separately. The data generated by this study could then be used to optimize the clinical application of TDF and provide new evidence for management of the HBV infections following failure of multiple NAs. The result of this study will help Chinese physicians better manage the CHB patients following failure of multiple NAs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tenofovir Disoproxil Fumarate | Experimental | Drug: Tenofovir disoproxil fumarateAll enrolled subjects will receive open label TDF at a dose of 300 milligram (mg) orally once daily during the study period. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged between 18-65years (inclusive). Male or female; a female is eligible to enter and participate in this study if she is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
- Child-bearing potential, has a negative serum pregnancy test at baseline, and agrees to one of the following methods for avoidance of pregnancy during the period of the study and until 30 days after last dose of study medication: Oral contraceptive, either combined or progestogen alone, Injectable progestogen, Implants of levonorgestrel, Oestrogenic vaginal ring, Percutaneous contraceptive patches., Intrauterine device (IUD) or intrauterine system (IUS) showing that the expected failure rate is less than 1% per year as stated in the IUD or IUS product label, Has a male partner who is sterilised, Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film /cream/suppository).
- The ability to understand and sign a written informed consent prior to any study-related procedure and comply with the requirements of the study.
- Positive HBsAg for more than 6 months, and anti-HBs negative.
- Serum HBV DNA level >=200 IU/mL at study screening (Use central lab results).
Key exclusion criteria (16 listed)
- Hepatocellular carcinoma as evidenced by one of the following: Suspicious foci on ultrasound or radiological examination, Normal ultrasound but a history of rising serum alpha-fetoprotein and serum alpha-fetoprotein >20 nanogram (ng) per mL at screening.
- Clinical signs of decompensated liver disease at baseline. These may include but are not limited to:Total serum bilirubin >1.5 x Upper limit of the normal range (ULN), International Normalized Ratio >1.3, Serum albumin <32grams per Liter (g/L), History of clinical hepatic decompensation (e.g., ascites, variceal bleeding, or encephalopathy).
- Creatinine clearance less than 70 milliliter per minutes (mL/min).
- Alanine aminotransferase >10 times ULN at screening or history of acute exacerbation leading to transient decompensation.
- Haemoglobin <8 grams per deciliter (g/dL), absolute neutrophil count <1.0 x 10^9 per Liter, platelets <75 x 10^9 per Liter.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir disoproxil fumarateTenofovir disoproxil fumarate tablets supplied will be white, almond-shaped, film-coated tablets containing 300 mg of TDF. Each tablet contains the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, pregelatinised starch, croscarmellose sodium, and magnesium stearate. | Drug | Tenofovir Disoproxil Fumarate |
Primary outcome
Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <20 International Unit Per Milliliter (IU/mL) at Week 144
Time frame: At Week 144
HBV DNA level were analyzed using the sensitive HBV test in central laboratory using Roche cobas Taqman HBV test from the blood samples collected at Week 144. A 95 percent confidence interval (CI) was constructed by normal approximation and continuity correction method. Percentage of participants with serum HBV DNA <20 IU/mL at Week 144 have been presented. The Modified Intent-to-treat (mITT) Population was defined as all recruited participants who received at least one dose of study medication.
17 secondary outcomes
Percentage of Participants With Serum HBV DNA <20 IU/mL and Serum HBV DNA <69 IU/mL at Weeks 48 and 96
Time frame: At Weeks 48 and 96
Percentage of Participants in the Subgroup With Confirmed Multi-drug Resistance Mutations at Baseline With Serum HBV DNA <20 IU/mL and Serum HBV DNA <69 IU/mL at Weeks 48, 96 and 144
Time frame: At Weeks 48, 96, and 144
Change From Baseline in Logarithm to the Base 10 (Log 10) Reduction in Serum HBV DNA at Week 48, 96 and 144
Time frame: Baseline (Day 0) and at Weeks 48,96, and 144
Percentage of Hepatitis B e Antigen (HBeAg) Positive Participants Achieving HBeAg Loss, HBeAg Seroconversion or Hepatitis B s Antigen (HBsAg) Loss and HBsAg Seroconversion at Weeks 48, 96, and 144
Time frame: At Weeks 48, 96 and 144
Percentage of HBeAg Negative Participants Achieving HBsAg Loss and HBsAg Seroconversion at Weeks 48, 96, and 144
Time frame: At Weeks 48,96, and 144
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 48, 96, and 144 in Participants Who Had Abnormal ALT at Baseline
Time frame: At Weeks 48, 96, and 144
Percentage of Participants Who Experienced Viral Breakthrough up to Week 144
Time frame: At Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120,132, and 144
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs
Time frame: Up to Week 144
Change From Baseline in Hematology Parameters: White Blood Cells (WBC), Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets
Time frame: Baseline (Day 0) and at Weeks 24, 48, 72, 96, 120 and 144
Change From Baseline in Hemoglobin (Hb)
Time frame: Baseline (Day 0) and at Weeks 24, 48, 72, 96, 120 and 144
Change From Baseline in Red Blood Cells (RBC)
Time frame: Baseline (Day 0) and at Weeks 24, 48, 72, 96, 120 and 144
Change From Baseline in Chemistry Parameters: ALT, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-Glutamyltransferase (GGT), Creatinine Phosphokinase (CK), Lactose Dehydrogenase (LDH)
Time frame: Baseline (Day 0) and at Weeks 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameters: Total Billirubin, Direct Bilirubin, Serum Creatinine
Time frame: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameters: Albumin, Total Protein
Time frame: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameter: Blood Urea Nitrogen (BUN), Potassium, Sodium, Chloridian, Phosphorus, Calcium and Fasting Blood Glucose.
Time frame: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameter: Creatinine Clearance Rate
Time frame: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline (Day 0) and at Weeks, 12,24,36,48,60,72,84,96,108,120,132,and 144
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tenofovir disoproxil fumarate in people with Hepatitis B, Chronic, run by GlaxoSmithKline at 12 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Serum Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <20 International Unit Per Milliliter (IU/mL) at Week 144 (time frame: At Week 144). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2019.