Clinical trial NCT04846491: A Study of Peginterferon Alfa-2b Combined With TDF in Patients With Chronic Hepatitis B
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis B
Keywords: peginterferon alfa-2b injection
interferon alfa
nucleos(t)ide
NUCs
NAs
chronic hepatitis B
Lead sponsor: Xiamen Amoytop Biotech Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking University First Hospital
First posted: 2021-04-15
Enrollment: 475
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients with HBsAg negative.
timeFrame: 24 weeks post treatment.
Secondary outcomes:
measure: Changes of HBsAg level from baseline.
timeFrame: up to 168 weeks.
measure: Proportion of patients with HBsAg seroconversion.
timeFrame: up to 168 weeks.
measure: Proportion of patients with HBeAg negative.
timeFrame: up to 168 weeks
measure: Proportion of patients with HBeAg seroconversion.
timeFrame: up to 168 weeks.
measure: Changes of HBeAg level from baseline.
timeFrame: up to 168 weeks.
measure: Proportion of patients with HBV DNA undetectable.
timeFrame: up to 168 weeks.
measure: Changes of HBV DNA level from baseline.
timeFrame: up to 168 weeks.
measure: Proportion of patients with ALT normalization.
timeFrame: up to 168 weeks.
measure: Proportion of patients with liver fibrosis.
timeFrame: up to 168 weeks.
measure: Proportion of patients with liver cirrhosis.
timeFrame: up to 168 weeks.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Youan Hospital, Capital Medical University
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: The fifth medical center of PLA General Hospital
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: Public Health Clinical Center of Chengdu
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hosipital of Fujian Medical University
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Fuzhou
country: China
facility: The Ninth Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army
city: Guangzhou
country: China
facility: Guangzhou Eighth People's Hospital
city: Guangzhou
country: China
facility: The Third Affiliated Hospital,SUN YAT-SEN University
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital/The First Affiliated Hospital of Nanjing University Medical School
city: Shanghai
country: China
facility: Huashan Hospital affiliated to Fudan University
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
city: Shenzhen
country: China
facility: Peiking University Shenzhen Hospital
city: Shenzhen
country: China
facility: The Third People's Hospital of shenzhen
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
city: Tianjin
country: China
facility: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
city: Urumqi
country: China
facility: Traditional Chinese Medicine hospital of Xinjiang Uygur Autonomous Region
city: Wuhan
country: China
facility: Tongji Hospital/Tongji Medical College Huazhong University of Science & Technology
city: Xi'an
country: China
facility: Tangdu Hospital
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xiamen
country: China
facility: Xiamen Hospital of Traditional Chinese Medicine
city: Yanbian
country: China
facility: Yanbian University Hospital/Yanbian Hospital
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
Study officials:
affiliation: Peking University First Hospital
name: Guiqiang Wang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: