Clinical trial NCT05797714: The Effectiveness and Safety of TMF in the Treatment of Chronic Hepatitis B Patients With Normal ALT.
Official title: A Prospective, Randomized, Blank Control, Multicenter Study to Evaluate the Efficacy and Safety of Alanine Aminotransferase（TMF）in the Treatment of Chronic Hepatitis B Patients With Normal Alanine Aminotransferase.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: HBV Infection
Chronic Hepatitis b
Keywords: Normal Alanine Aminotransferase
Treatment
Effectiveness
Safety
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu Hansoh Pharmaceutical Co., Ltd.
First posted: 2023-04-04
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The subjects were randomly divided into two groups. One group received TMF treatment for 48 weeks. Aonther group received no antiviral therapy and served as a blank control.
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, open, blank controlled trial ，in order to evaluate the effectiveness and safety of Amibufenamide（TMF） in the treatment of chronic hepatitis B virus infection patients with normal ALT .

Detailed description: Although the indications for antiviral therapy for patients with chronic hepatitis B have been gradually expanded in different guidelines, antiviral treatment efficacy remains unclear among patients with alanine aminotransferase (ALT) \< 1 upper limits of normal (ULN). This study aimed to evaluate the the effectiveness and safety of TMF for these patients.

Tenofovir amibufenamide (TMF; codename: HS-10234), another formulation of tenofovir, shared the same ProTide technology as tenofovir alafenamide, which can provide more efficient intracellular delivery than TDF.

Eligibility criteria: Inclusion Criteria:

1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study screening.
2. Male and non-pregnant, non-lactating females, from 18 up to 65 years of age (based on the date of the screening visit). A negative serum pregnancy test at screening is required for female subjects of childbearing potential.
3. Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months).
4. Normal alanine aminotransferase: serum HBV DNA \>20 IU/mL and serum ALT level ≤ULN (40 IU/L) during screening.
5. Treatment-naive subjects will be eligible for enrollment.
6. Must be willing and able to comply with all study requirements.

Exclusion Criteria:

1. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
2. Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study.
3. Co-infection with HCV virus, HIV, HEV or HDV or combined with autoimmune liver disease, metabolism-related fatty liver disease, drug-induced liver injury;
4. Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging).
5. Any history of, or current evidence of, clinical hepatic decompensation (e.g. ascites encephalopathy or variceal hemorrhage) or liver stiffness over 9kpa measured by TE.
6. Abnormal hematological and biochemical parameters, including:

   Hemoglobin \< 10 g/dl Absolute neutrophil count \< 0.75 × 10\^9/L Platelets ≤ 50 × 10\^9/L AST \> 10 × ULN Total Bilirubin \> 2.5 × ULN Albumin \< 3.0 g/dL INR \> 1.5 × ULN (unless stable on anticoagulant regimen) eGFR\<50mL/min
7. Received solid organ or bone marrow transplant.
8. Malignancy within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc).
9. Currently receiving therapy with immunomodulators (e.g. corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.
10. Complicated with uncontrollable cardiovascular and cerebrovascular diseases.
11. Subjects on prohibited concomitant medications. Subjects on prohibited medications, otherwise eligible, will need a wash out period of at least 30 days,Known hypersensitivity to study drugs, metabolites, or formulation excipients.
12. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
13. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.

Primary outcomes:
measure: Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL
timeFrame: Week 48
Secondary outcomes:
measure: Evaluation the change from Baseline in HBV DNA
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the proportion of Patients Achieving HBsAg Seroconversion
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the proportion of Patients Achieving HBeAg Seroconversion
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the proportion of Patients Achieving HBeAg Loss
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the change from Baseline in HBsAg
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the percentage of Participants with resistance
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the change from Baseline in liver fibrosis
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the proportion of Patients with get hepatitis acute attack（ALT >5 ULN (40 IU/L)）
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL
timeFrame: Week 96，Week 144
measure: Evaluation the change from Baseline in Bone biomarker（β-CTX and P1NP）
timeFrame: Week 48，Week 96，Week 144
measure: Evaluation the change from Baseline in sCR
timeFrame: Week 48，Week 96，Week 144
measure: AE ,SAE
timeFrame: Week 48，Week 96，Week 144
Other outcomes:
Locations:
city: Changsha
country: China
facility: The Second Xiangya Hospital, Central South University
state: Hunan
city: Beijing
country: China
facility: Beijing You'An Hospital, Capital Medical University
city: Dongyang
country: China
facility: People's Hospital of Dongyang City
city: Fuyang
country: China
facility: Fuyang Second People's Hospital
city: Hangzhou
country: China
facility: The First People's Hospital of Xiaoshan District, Hangzhou, Zhejiang Province
city: LiShui
country: China
facility: LiShui People's Hospital of Zhejiang Province
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjin
country: China
facility: Jiangsu Province Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
city: Shanghai
country: China
facility: Shanghai East Hospital
city: Suzhou
country: China
facility: The Fifth People's Hospital of Suzhou
city: Wuxi
country: China
facility: The Fifth People's Hospital of Wuxi
Study officials:
References:
citation: Liu Z, Jin Q, Zhang Y, Gong G, Wu G, Yao L, Wen X, Gao Z, Huang Y, Yang D, Chen E, Mao Q, Lin S, Shang J, Gong H, Zhong L, Yin H, Wang F, Hu P, Xiao L, Li C, Wu Q, Sun C, Niu J, Hou J; TMF Study Group. Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B. Aliment Pharmacol Ther. 2021 Nov;54(9):1134-1149. doi: 10.1111/apt.16611. Epub 2021 Sep 29.