A Study of Peginterferon Alfa-2b Combined With TDF in Patients With Chronic Hepatitis B

Chronic Hepatitis B Clinical Trial

Official title:

A Multi-center, Randomized, Blinded Study to Evaluate the Efficacy and Safety of Peginterferon Alfa-2b Injection Combined With Tenofovir Disoproxil Fumarate Tablets in Patients With Chronic Hepatitis B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04846491
• Other study ID #: TB1901IFN
• Status: Completed
• Phase: Phase 3
• Start date: December 4, 2019
• Est. completion date: December 7, 2023

Study information

• Verified date: August 2023
• Source: Xiamen Amoytop Biotech Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Current clinical practices has shown promising prospects of the therapy strategy of interferon combined with nucleos(t)ides in patients with chronic hepatitis B, but the safety and efficacy has not been fully studied. This study is aimed to exploit the safety and efficacy of the study drug, Peginterferon alfa-2b injection, with nucleos(t)ide (NAs), tenofovir disoproxil fumarate tablets (TDF), in the patients with hepatitis B, who has previously treated with nucleos(t)ides and who are treatment naïve.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 475
• Est. completion date: December 7, 2023
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Understand and sign the informed consent form voluntarily.

• Age between 18 and 65 years (including 18 and 65), no gender limit.

• HBsAg-positive for at least 6 months or other evidence supporting chronic infection with hepatitis B virus.

• HBsAg positive at screening.

• For NAs treated patients: Who should have continuously taken NAs for at least 9 months prior to screening, and are currently receiving the NAs. Simultaneously, the patients should have achieved the following criteria: HBsAg<1500IU/mL, HBV DNA<100IU/ml, HBeAg<10s/co at screening.

• For treatment naive patients: HBV DNA=1×10^4IU/ml, and 2×ULN (upper limit of normal) =ALT=10×ULN at screening.

• Pregnancy test of female of childbearing must be negative within 24 hours before the first medication, and the subjects (male and female) should take effective contraceptive measures during the whole study period.

Exclusion Criteria:

• Women who are pregnant, breastfeeding or planning to pregnant during the study period.

• Subjects with neuropsychiatric diseases and/or neuropsychiatric family history, especially depression, anxiety, or mania schizophrenia.

• Co-infected with Hepatitis A, Hepatitis C, Hepatitis D, Hepatitis E, or HIV.

• Chronic hepatitis other than hepatitis B, e.g. alcoholic hepatitis, drugs-induced hepatitis, or autoimmune hepatitis, etc.

• Moderate to severe steatohepatitis.

• Evidence of acute severe hepatitis, e.g. ALT>10×ULN, significantly increasing in ALT accompanied by elevated bilirubin, etc.

• Evidence of liver decompensation, e.g. total bilirubin higher than 2×ULN, albumin lower than 35g/L, prothrombin time is 3 seconds longer than the upper limit of normal, prothrombin activity lower than 60%, or history of decompensated liver cirrhosis, etc.

• Evidence of hepatocellular carcinoma, or AFP>1×ULN.

• Significant kidney diseases, including acute nephritis, chronic nephritis, renal insufficiency, nephrotic syndrome, etc. or serum creatinine higher than upper limit of normal.

• Neutrophil count less than 1.5×10^9/L, or platelet count less than 90×10^9/L at screening.

• Serum phosphorus lower than 0.8mmol/L.

• Antinuclear antibody (ANA) exceeds 1:100.

• Autoimmune disease, including psoriasis, systemic lupus erythematosus, etc.

• Subjects with endocrine system disease, including thyroid, Diabetes mellitus, etc.

• Poorly controlled hypertension (blood pressure =140/90 mmHg).

• Subjects with severe heart disease, especially those with unstable angina or poorly controlled heart disease within 6 months prior to screening.

• Severe retinopathy or any other severe diseases in the eyes.

• Subject who had ever received organ transplants or are planning to receive organ transplant.

• For NAs-treated patients: who have received standard treatment of interferon products within 6 months prior to screening .

• For treatment naive patients: who have ever received standard treatment of interferon products, or who have ever received NAs within 6 months prior to screening.

• Subject who are allergic to interferon, tenofovir, or any excipients, or meet any of the contraindications described in the drug instructions.

• Subjects who participated in any other interventional trials within 3 months prior to screening, or with any other conditions which in the opinion of the investigator precluding enrollment from the study.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Peginterferon alfa-2b injection
Peginterferon alfa-2b injection (high dose) will be weekly subcutaneous injected for 8 weeks and then stop for 4 weeks, 12 week a cycle, up to 12 cycles (144 weeks) at most. TDF will be taken orally during the whole treatment period. And then followed for 24 weeks after treatment.
• Peginterferon alfa-2b injection
Peginterferon alfa-2b injection (low dose) will be weekly subcutaneous injected for 8 weeks and then stop for 4 weeks, 12 week a cycle, up to 12 cycles (144 weeks) at most. TDF will be taken orally during the whole treatment period. And then followed for 24 weeks after treatment.
• TDF
Patients will take TDF orally for the first 48 weeks, and then one can choose to continue the single-TDF treatment up to 144 weeks, or may choose to change to receive peginterferon alfa-2b combined TDF therapy for the later 96 weeks, peginterferon alfa-2b will be weekly subcutaneous injected for 8 weeks and then stop for 4 weeks, 12 weeks a cycle. And then followed for 24 weeks after treatment.
• Peginterferon alfa-2b injection
Peginterferon alfa-2b injection will be weekly subcutaneous injected for 8 weeks and then stop for 4 weeks, 12 week a cycle, up to 12 cycles (144 weeks) at most. TDF will be taken orally during the whole treatment period. And then followed for 24 weeks after treatment.

Locations

Country	Name	City	State
China	Beijing Ditan Hospital, Capital Medical University	Beijing
China	Beijing Youan Hospital, Capital Medical University	Beijing
China	Peking University First Hospital	Beijing
China	The fifth medical center of PLA General Hospital	Beijing
China	The Second Xiangya Hospital of Central South University	Changsha
China	Xiangya Hospital Central South University	Changsha
China	Public Health Clinical Center of Chengdu	Chengdu
China	Sichuan Provincial People's Hospital	Chengdu
China	Mengchao Hepatobiliary Hosipital of Fujian Medical University	Fuzhou
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou
China	The Ninth Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army	Fuzhou
China	Guangzhou Eighth People's Hospital	Guangzhou
China	The Third Affiliated Hospital,SUN YAT-SEN University	Guangzhou
China	The Fourth Affiliated Hospital of Harbin Medical University	Harbin
China	The First Affiliated Hospital of Anhui Medical University	Hefei
China	Nanjing Drum Tower Hospital/The First Affiliated Hospital of Nanjing University Medical School	Nanjing
China	Huashan Hospital affiliated to Fudan University	Shanghai
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai
China	The Sixth People's Hospital of Shenyang	Shenyang
China	Peiking University Shenzhen Hospital	Shenzhen
China	The Third People's Hospital of shenzhen	Shenzhen
China	The First Hospital of Shanxi Medical University	Taiyuan
China	First Teaching Hospital of Tianjin University of Traditional Chinese Medicine	Tianjin
China	Tianjin Third Central Hospital	Tianjin
China	The First Affiliated Hospital of Xinjiang Medical University	Urumqi
China	Traditional Chinese Medicine hospital of Xinjiang Uygur Autonomous Region	Urumqi
China	Tongji Hospital/Tongji Medical College Huazhong University of Science & Technology	Wuhan
China	Tangdu Hospital	Xi'an
China	The First Affiliated Hospital of Xian Jiaotong University	Xi'an
China	The First Affiliated Hospital of Xiamen University	Xiamen
China	Xiamen Hospital of Traditional Chinese Medicine	Xiamen
China	Yanbian University Hospital/Yanbian Hospital	Yanbian
China	Henan Provincial People's Hospital	Zhengzhou

Sponsors (2)

Lead Sponsor	Collaborator
Xiamen Amoytop Biotech Co., Ltd.	Peking University First Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with HBsAg negative.		24 weeks post treatment.
Secondary	Changes of HBsAg level from baseline.		up to 168 weeks.
Secondary	Proportion of patients with HBsAg seroconversion.		up to 168 weeks.
Secondary	Proportion of patients with HBeAg negative.		up to 168 weeks
Secondary	Proportion of patients with HBeAg seroconversion.		up to 168 weeks.
Secondary	Changes of HBeAg level from baseline.		up to 168 weeks.
Secondary	Proportion of patients with HBV DNA undetectable.		up to 168 weeks.
Secondary	Changes of HBV DNA level from baseline.		up to 168 weeks.
Secondary	Proportion of patients with ALT normalization.		up to 168 weeks.
Secondary	Proportion of patients with liver fibrosis.		up to 168 weeks.
Secondary	Proportion of patients with liver cirrhosis.		up to 168 weeks.