Clinical trial NCT05755776: The Efficacy and Safety of Tenofovir Amibufenamide to Treat Low-level Viraemia After Entecavir Treatment
Official title: To Evaluate the Efficacy and Safety of Tenofovir Amibufenamide in Chronic Hepatitis B (CHB) Patients With Low-level Viraemia (LLV) After Entecavir Treatment
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis B
Keywords: Chronic Hepatitis b
Entecavir
Tenofovir Amibufenamide
Low-level viraemia
Lead sponsor: The Second Affiliated Hospital of Chongqing Medical University
Sponsor class: OTHER
Collaborators: name: Jiangsu Hansoh Pharmaceutical Co., Ltd.
First posted: 2023-03-06
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population was chronic hepatitis B patients with LLV (HBV DNA from 20-to 2000IU/mL) of ETV treatment from multiple centers across mainland China.

Brief summary: The goal of this observational study is to explore the efficacy and safety of Tenofovir Amibufenamide (TMF) in Entecavir (ETV) treated chronic hepatitis B patients with low-level viraemia. The main question it aims to answer is:

* The efficacy and safety of TMF in chronic hepatitis B patients with low-level viraemia.
* What is the appropriate treatment for ETV treated chronic hepatitis B patients with low-level viraemia.

Participants will choose to maintain their original regimen (ETV) or switch to TMF After being fully informed of the benefits and risks of treatment.

Researchers will compare ETV and TMF to see if there is a difference in the efficacy of the two drugs in chronic hepatitis B patients with low-level viraemia.


Eligibility criteria: Inclusion Criteria:

1. Must be able to understand and sign a written informed consent, which must be obtained prior to screening.
2. Male and non-pregnant, non-lactating female subjects who have reached the age of 18-65 years (based on the date of signed informed consent). Female subjects of childbearing age with a negative serum pregnancy test.
3. Documented signs of chronic HBV infection (e.g., HBsAg positive for more than 6 months.
4. Subjects treated with ETV over 1 year will be able to be enrolled in the study.
5. Subjects with 20 ≤ HBV-DNA \< 2000 IU/mL at screening (including intermittent and continuous low-level viraeima).
6. Must be willing and able to comply with all study requirements.

Exclusion Criteria:

1. Female patients who are pregnant or breastfeeding or who plan to become pregnant during the study period.
2. Men and women of childbearing potential who are unwilling to use an "effective" method of contraception as defined in the protocol during the study period.
3. Co-infection with HAV HCV, HIV, HDV or HEV; or co-infection with autologous liver, metabolism-related fatty liver, or drug-induced liver injury.
4. Diagnosis of hepatocellular carcinoma by imaging (with evidence of hepatocellular carcinoma)
5. Patients who have received a solid organ or bone marrow transplant
6. History of malignancy within 5 years prior to screening, except for specific tumors cured by surgical resection (basal cell dermal skin cancer, etc.); patients evaluated for probable malignancy were ineligible.
7. Currently receiving treatment with immunomodulators (e.g., corticosteroids), investigational drugs, nephrotoxic drugs, or drugs capable of regulating renal excretion. Drugs that modulate renal excretion.
8. Renal, cardiovascular, pulmonary, or neurological disease that is considered severe by the investigator.
9. Severe bone disease (e.g., osteochondrosis, chronic osteomyelitis, osteogenesis imperfecta, chondromalacia) or multiple fractures.
10. Subjects receiving a contraindicated combination drug (subjects receiving a contraindicated drug require a minimum 30-day washout period) and known hypersensitivity reactions to study drugs, metabolites or formulation excipients.
11. Current alcohol or drug abuse that, in the investigator's judgment, may interfere with the subject's compliance with study requirements.
12. Any other clinical condition that, in the opinion of the investigator, would render the subject unsuitable for the study or unable to comply with the dosing requirements medical condition or prior treatment.
13. Prior or existing clinical liver failure (Child-Pugh score ≥ grade B).

Primary outcomes:
measure: The proportions of undetectable HBV DNA in patients treated with ETV and TMF at week 48.
timeFrame: 48 weeks
Secondary outcomes:
measure: The proportions of undetectable HBV DNA in patients treated with ETV and TMF at week 24.
timeFrame: 24 weeks
measure: The proportions of ALT normalization in patients treated with ETV and TMF at week 24 and 48.
timeFrame: 24 weeks and 48 weeks
measure: Comparing pgRNA levels from baseline at week 24 and 48.
timeFrame: 24 weeks and 48 weeks
measure: Comparing HBcrAg levels from baseline at week 24 and 48.
timeFrame: 24 weeks and 48 weeks
measure: The proportions of undetectable pgRNA in patients treated with ETV and TMF at week 24 and 48.
timeFrame: 24 weeks and 48 weeks
measure: The proportions of undetectable HBcrAg in patients treated with ETV and TMF at week 24 and 48.
timeFrame: 24 weeks and 48 weeks
measure: Comparing degree of liver fibrosis from baseline at week 24 and 48.
timeFrame: 24 weeks and 48 weeks
measure: Comparing the change of creatinine clearance rate from baseline at week 24 and 48.
timeFrame: 24 weeks and 48 weeks
measure: The types, incidence and severity of adverse events and serious adverse events during treatment were evaluated in both groups
timeFrame: Week 48
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: Chongqing University Three Gorges Central Hospital
city: Guangxi
country: China
facility: Affiliated Hospital of Guangxi Medical University
city: Jilin
country: China
facility: Hepatobiliary disease of Jilin Province
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
city: Kunming
country: China
facility: the Second People's Hospital of Yunnan Province
city: Nanjing
country: China
facility: Nanjing Second Hospital
city: Ningbo
country: China
facility: The Second Hospital of Ningbo
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Shanghai
country: China
facility: Shuguang Hospital, Shanghai, China.
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
city: Taicang
country: China
facility: The First People's Hospital of Taicang
city: Zibo
country: China
facility: The Fourth People's Hospital of Zibo
Study officials:
affiliation: The Second Affiliated Hospital of Chongqing Medical University
name: Peng Hu, phD
role: STUDY_DIRECTOR
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