The Efficacy and Safety of Tenofovir Amibufenamide to Treat Low-level Viraemia After Entecavir Treatment

NCT05755776 | Unknown

• 1 other identifier: HS-10234-A005
• Study Type: observational
• Target: 204
• Locations: 1 country
• Sites: 13

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.

Conditions

Chronic Hepatitis B

Keywords

Chronic Hepatitis b; Entecavir; Tenofovir Amibufenamide; Low-level viraemia

Outcome Measures

Primary Outcomes (1)

• The proportions of undetectable HBV DNA in patients treated with ETV and TMF at week 48.

  Undetectable HBV DNA is defined as below 20 IU/mL.

  48 weeks

Secondary Outcomes (9)

• The proportions of undetectable HBV DNA in patients treated with ETV and TMF at week 24.

  24 weeks

• The proportions of ALT normalization in patients treated with ETV and TMF at week 24 and 48.

  24 weeks and 48 weeks

• Comparing pgRNA levels from baseline at week 24 and 48.

  24 weeks and 48 weeks

• Comparing HBcrAg levels from baseline at week 24 and 48.

  24 weeks and 48 weeks

• The proportions of undetectable pgRNA in patients treated with ETV and TMF at week 24 and 48.

  24 weeks and 48 weeks

Study Arms (2)

ETV group

Participants in this group will continue ETV daily until the end of the study.

TMF group

Participants in this group will switch to TMF 25 mg, daily until the end of the study.

Drug: TMF

Interventions

TMF DRUG

switch ETV to TMF

Also known as: Heng Mu

TMF group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Must be able to understand and sign a written informed consent, which must be obtained prior to screening.
• 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.
• Documented signs of chronic HBV infection (e.g., HBsAg positive for more than 6 months.
• Subjects treated with ETV over 1 year will be able to be enrolled in the study.
• Subjects with 20 ≤ HBV-DNA \< 2000 IU/mL at screening (including intermittent and continuous low-level viraeima).
• Must be willing and able to comply with all study requirements.

You may not qualify if:

• Female patients who are pregnant or breastfeeding or who plan to become pregnant during the study period.
• 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.
• Co-infection with HAV HCV, HIV, HDV or HEV; or co-infection with autologous liver, metabolism-related fatty liver, or drug-induced liver injury.
• Diagnosis of hepatocellular carcinoma by imaging (with evidence of hepatocellular carcinoma)
• Patients who have received a solid organ or bone marrow transplant
• 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.
• Currently receiving treatment with immunomodulators (e.g., corticosteroids), investigational drugs, nephrotoxic drugs, or drugs capable of regulating renal excretion. Drugs that modulate renal excretion.
• Renal, cardiovascular, pulmonary, or neurological disease that is considered severe by the investigator.
• Severe bone disease (e.g., osteochondrosis, chronic osteomyelitis, osteogenesis imperfecta, chondromalacia) or multiple fractures.
• 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.
• Current alcohol or drug abuse that, in the investigator's judgment, may interfere with the subject's compliance with study requirements.
• 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.
• Prior or existing clinical liver failure (Child-Pugh score ≥ grade B).

Sponsors & Collaborators

• The Second Affiliated Hospital of Chongqing Medical University: lead
• Jiangsu Hansoh Pharmaceutical Co., Ltd.: collaborator

Study Sites (13)

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400010, China

RECRUITING

Chongqing University Three Gorges Central Hospital

Chongqing, 400010, China

NOT YET RECRUITING

Affiliated Hospital of Guangxi Medical University

Guangxi, China

NOT YET RECRUITING

Hepatobiliary disease of Jilin Province

Jilin, China

NOT YET RECRUITING

The First People's Hospital of Yunnan Province

Kunming, China

NOT YET RECRUITING

the Second People's Hospital of Yunnan Province

Kunming, China

NOT YET RECRUITING

Nanjing Second Hospital

Nanjing, China

NOT YET RECRUITING

The Second Hospital of Ningbo

Ningbo, China

RECRUITING

Shanghai East Hospital

Shanghai, China

RECRUITING

Shuguang Hospital, Shanghai, China.

Shanghai, China

NOT YET RECRUITING

The Sixth People's Hospital of Shenyang

Shenyang, China

NOT YET RECRUITING

The First People's Hospital of Taicang

Taicang, China

NOT YET RECRUITING

The Fourth People's Hospital of Zibo

Zibo, China

NOT YET RECRUITING

Related Publications (10)

• Liu J, Liang W, Jing W, Liu M. Countdown to 2030: eliminating hepatitis B disease, China. Bull World Health Organ. 2019 Mar 1;97(3):230-238. doi: 10.2471/BLT.18.219469. Epub 2019 Jan 28.

  PMID: 30992636 BACKGROUND

• Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.

  PMID: 16391218 BACKGROUND

• Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep.29800. No abstract available.

  PMID: 29405329 BACKGROUND

• Sun Y, Wu X, Zhou J, Meng T, Wang B, Chen S, Liu H, Wang T, Zhao X, Wu S, Kong Y, Ou X, Wee A, Theise ND, Qiu C, Zhang W, Lu F, Jia J, You H. Persistent Low Level of Hepatitis B Virus Promotes Fibrosis Progression During Therapy. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2582-2591.e6. doi: 10.1016/j.cgh.2020.03.001. Epub 2020 Mar 6.

  PMID: 32147592 BACKGROUND

• Kim JH, Sinn DH, Kang W, Gwak GY, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment. Hepatology. 2017 Aug;66(2):335-343. doi: 10.1002/hep.28916. Epub 2016 Dec 24.

  PMID: 28012257 BACKGROUND

• Wang J, Sheng Q, Ding Y, Chen R, Sun X, Chen X, Dou X, Lu F. HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficient. J Hepatol. 2018 Apr;68(4):847-849. doi: 10.1016/j.jhep.2017.10.030. Epub 2017 Nov 4. No abstract available.

  PMID: 29113914 BACKGROUND

• Yuen MF, Seto WK, Fung J, Wong DK, Yuen JC, Lai CL. Three years of continuous entecavir therapy in treatment-naive chronic hepatitis B patients: VIRAL suppression, viral resistance, and clinical safety. Am J Gastroenterol. 2011 Jul;106(7):1264-71. doi: 10.1038/ajg.2011.45. Epub 2011 Mar 1.

  PMID: 21364549 BACKGROUND

• Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol. 2019 Jun;25(2):93-159. doi: 10.3350/cmh.2019.1002. Epub 2019 Jun 12. No abstract available.

  PMID: 31185710 BACKGROUND

• Ogawa E, Nomura H, Nakamuta M, Furusyo N, Koyanagi T, Dohmen K, Ooho A, Satoh T, Kawano A, Kajiwara E, Takahashi K, Azuma K, Kato M, Shimoda S, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group. Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B. Liver Int. 2020 Jul;40(7):1578-1589. doi: 10.1111/liv.14482. Epub 2020 Apr 30.

  PMID: 32304611 BACKGROUND

• 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.

  PMID: 34587302 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Peng Hu, phD

  The Second Affiliated Hospital of Chongqing Medical University

  STUDY DIRECTOR

Central Study Contacts

Jie Wu

CONTACT

+86 18652100702; wuj6@hspharm.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 6, 2023
• Study Start: March 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: September 21, 2023

Record last verified: 2022-10

Locations

CN (13)