Last updated: 11/30/2020 17:02:06
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
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Proportion of subjects with serum HBV DNA <20 IU/mL at Week 144
Timeframe: Week 144
Secondary outcomes:
Proportion of subjects with serum HBV DNA <20 IU/mL at Week 48 and 96
Timeframe: Week 48 and Week 96
Log 10 reduction in serum HBV DNA at Week 48, 96 and144
Timeframe: Week 48, Week 96, Week 144
Proportion of HBeAg positive subjects achieving HBeAg loss, HBeAg seroconversion or HBsAg loss and HBsAg seroconversion at Week 48, 96, and 144.
Timeframe: Week 48, Week 96, Week 144
Proportion of HBeAg negative subjects achieving HBsAg loss and HBsAg seroconversion at Week 48, 96, and 144
Timeframe: Week 48, Week 96, Week 144
Proportion of subjects achieving with ALT normalization at Week 48, 96, and 144 in subjects who have abnormal ALT at baseline
Timeframe: Week 48,Week 96,Week 144
Incidences of subjects who experience viral breakthrough up to week 144
Timeframe: Up to week 144
Proportion of subjects in the subgroup with confirmed multi-drug resistance mutations at baseline with serum HBV DNA <20 IU/ml at week 48, 96 and 144
Timeframe: Week 48,Week 96,Week 144
Safety as assessed by adverse events
Timeframe: Up to week 144
Safety as assessed by clinical laboratory tests
Timeframe: Up to week 144
Interventions:
Drug: Tenofovir disoproxil fumarate
Enrollment:
213
Observational study model:
Not applicable
Primary completion date:
2018-14-08
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Hepatitis B, Chronic
Product
tenofovir disoproxil fumarate
Collaborators
Not applicable
Study date(s)
March 2015 to August 2018
Type
Interventional
Phase
4
Participation criteria
Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
No
- 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).
- 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).
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
Exclusion criteria:
- 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.
- 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 location(s)
Study documents
Statistical analysis plan
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2018-14-08
Actual study completion date
2018-14-08
Plain language summaries
Summary of results in plain language
Available language(s): English, Chinese (China)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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