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

Sponsor

Xiamen Amoytop Biotech Co., Ltd. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04846491

Collaborator

Peking University First Hospital (Other)

475

Enrollment

Locations

Arms

48.9

Anticipated Duration (Months)

14.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: Peginterferon alfa-2b injection Drug: Peginterferon alfa-2b injection Drug: TDF Drug: Peginterferon alfa-2b injection	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

475 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 4, 2019

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nucleot(s)ide-treated patients-Experimental Group 1	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.
Experimental: Nucleot(s)ide-treated patients-Experimental Group 2	Drug: 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.
Active Comparator: Nucleot(s)ide-treated patients-Control Group	Drug: 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.
Other: Treatment Naive Group	Drug: 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.

Outcome Measures

Primary Outcome Measures

Proportion of patients with HBsAg negative. [24 weeks post treatment.]

Secondary Outcome Measures

Changes of HBsAg level from baseline. [up to 168 weeks.]
Proportion of patients with HBsAg seroconversion. [up to 168 weeks.]
Proportion of patients with HBeAg negative. [up to 168 weeks]
Proportion of patients with HBeAg seroconversion. [up to 168 weeks.]
Changes of HBeAg level from baseline. [up to 168 weeks.]
Proportion of patients with HBV DNA undetectable. [up to 168 weeks.]
Changes of HBV DNA level from baseline. [up to 168 weeks.]
Proportion of patients with ALT normalization. [up to 168 weeks.]
Proportion of patients with liver fibrosis. [up to 168 weeks.]
Proportion of patients with liver cirrhosis. [up to 168 weeks.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Beijing Ditan Hospital, Capital Medical University	Beijing	China
2	Beijing Youan Hospital, Capital Medical University	Beijing	China
3	Peking University First Hospital	Beijing	China
4	The fifth medical center of PLA General Hospital	Beijing	China
5	The Second Xiangya Hospital of Central South University	Changsha	China
6	Xiangya Hospital Central South University	Changsha	China
7	Public Health Clinical Center of Chengdu	Chengdu	China
8	Sichuan Provincial People's Hospital	Chengdu	China
9	Mengchao Hepatobiliary Hosipital of Fujian Medical University	Fuzhou	China
10	The First Affiliated Hospital of Fujian Medical University	Fuzhou	China
11	The Ninth Hospital of the Joint Logistic Support Force of the Chinese People's Liberation Army	Fuzhou	China
12	Guangzhou Eighth People's Hospital	Guangzhou	China
13	The Third Affiliated Hospital,SUN YAT-SEN University	Guangzhou	China
14	The Fourth Affiliated Hospital of Harbin Medical University	Harbin	China
15	The First Affiliated Hospital of Anhui Medical University	Hefei	China
16	Nanjing Drum Tower Hospital/The First Affiliated Hospital of Nanjing University Medical School	Nanjing	China
17	Huashan Hospital affiliated to Fudan University	Shanghai	China
18	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	China
19	The Sixth People's Hospital of Shenyang	Shenyang	China
20	Peiking University Shenzhen Hospital	Shenzhen	China
21	The Third People's Hospital of shenzhen	Shenzhen	China
22	The First Hospital of Shanxi Medical University	Taiyuan	China
23	First Teaching Hospital of Tianjin University of Traditional Chinese Medicine	Tianjin	China
24	Tianjin Third Central Hospital	Tianjin	China
25	The First Affiliated Hospital of Xinjiang Medical University	Urumqi	China
26	Traditional Chinese Medicine hospital of Xinjiang Uygur Autonomous Region	Urumqi	China
27	Tongji Hospital/Tongji Medical College Huazhong University of Science & Technology	Wuhan	China
28	Tangdu Hospital	Xi'an	China
29	The First Affiliated Hospital of Xian Jiaotong University	Xi'an	China
30	The First Affiliated Hospital of Xiamen University	Xiamen	China
31	Xiamen Hospital of Traditional Chinese Medicine	Xiamen	China
32	Yanbian University Hospital/Yanbian Hospital	Yanbian	China
33	Henan Provincial People's Hospital	Zhengzhou	China