Study on an Optimal Antiviral Treatment in HBeAg Positive Chronic Hepatitis B Patients

Chronic Hepatitis Clinical Trial

Official title:

A Prospective, Randomized, Multicenter, Open-label Study of Optimal Antiviral Treatment in HBeAg Positive Chronic Hepatitis B Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03013556
• Other study ID #: SHDC12016101
• Status: Recruiting
• Phase: Phase 4
• Start date: November 2016
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2021
• Source: Ruijin Hospital
• Contact: Xinxin Zhang
• Email: zhangx[@]shsmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The current study is a prospective, randomized, open, multi-center investigation. The aim of the study is to investigate whether the HBeAg seroconversion rate can be improved if applying combination therapy in HBeAg positive CHB patients who has achieved HBVDNA<105copies/ml，HBsAg≤5000IU/ml, ALT≥ 2ULN or Liver histology G2S2.

Description:

The HBeAg positive chronic hepatitis B(CHB) subjects who has achieved HBV DNA<10*5copies/ml，HBsAg≤5000IU/ml, ALT≥ 2ULN or Liver histology G2S2 will be randomized to three groups. The subjects who go into group A will be treated by tenofovir disoproxil fumarate (TDF) for 96 weeks; The subjects who go into group B will be treated by TDF in the first 48 weeks, then will be treated by the combination of TDF and Peginterferon alfa-2a for another 48 weeks; The subjects who go into group C will be treated by the combination of TDF and Peginterferon alfa-2a for the first 48 weeks, then will be treated by TDF for another 48 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 31, 2021
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male and female patients with age =18 and =65 years;

2. There should be evidences that HBsAg and HBeAg have been positive for more than 6 months with HBsAb and HBeAb negative;HBsAg=50000IU/ml, ALT= 2ULN,Liver histology above G2S2 and HBV DNA=10*5 copies/mL;

3. Women without ongoing pregnancy or breast feeding and both women and men willing to take an effective contraceptive measure during the treatment;

4. Agree to participate in the study and sign the patient informed consent form.

Exclusion Criteria:

1. Treated by immunosuppressant,immunomodulator,Systemic cytotoxic drug,herbs or HBIg within 6 months prior to the first dose of treatment;

2. ALT=10 X ULN or total bilirubin =2 X ULN;

3. Allergic history to interferon;

4. Co-infection with active hepatitis A, hepatitis C, hepatitis D and/or human immunodeficiency virus (HIV);

5. Child-Pugh scores >7;

6. History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);

7. Pregnant or breast-feeding Women;

8. Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment or drug taking history;

9. ANC(absolute neutrophil count)<1.5x 10^9/L or PLT(platelet count)<90x 10^9/L

10. Creatinine over upper limit of normal;

11. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis that treated with antidepressant medication or a major tranquilizer at therapeutic doses respectively at any time prior to 3 months or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;

12. History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);

13. History of esophageal varices bleeding or other evidence of esophageal varices bleeding or other symptoms consistent with decompensated liver disease;

14. History of severe cardiac disease (e.g., New York Heart Association Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases);

15. Hemodialysis patients or patients with renal insufficiency;

16. History of a severe seizure disorder or current anticonvulsant use;

17. Major organ transplantation or other evidence of severe illness, malignancy, or any other conditions, which would make the patient, in the opinion of the investigator, unsuitable for the study;

18. History of thyroid disease poorly controlled on prescribed medications;

19. Evidence of severe retinopathy or clinically relevant ophthalmologic disorder;

20. History of other severe disease or evidence of other severe disease or any other illness or conditions that the investigator believe that patients are not suitable to join in the study;

21. Patients included in another trial or having been given investigational drugs within 12 weeks prior to screening;

22. AFP(alpha feto protein)>50ng/ml and/or evidence of hepatocellular carcinoma;

23. Other disease should exclusive considered by the investigator.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Group A, TDF
TDF for 96 weeks
• Group B:TDF then TDF and Peginterferon alfa-2a
Subjects will be treated by TDF in the first 48 weeks, then will be treated by the combination of TDF and Peginterferon alfa-2a for another 48 weeks
• Group C:TDF and Peginterferon alfa-2a then TDF
Subjects will be treated by the combination of TDF and Peginterferon alfa-2a for the first 48 weeks, then will be treated by TDF for another 48 weeks.

Locations

Country	Name	City	State
China	Xixi Hospital of Hangzhou	Hangzhou
China	Changhai Hospital	Shanghai
China	Hua shan Hospital,Fudan University	Shanghai
China	Infectious diesease hospital of Huangpu district in Shanghai	Shanghai
China	No.9 hospital of shanghai	Shanghai
China	Shanghai public health clinical center	Shanghai
China	Shuguang Hospital of Shanghai T.C.M	Shanghai
China	Tongren hospital Shanghai Jiaotong University School of medicine	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, Streinu-Cercel A, Wang JY, Idilman R, Reesink HW, Diculescu M, Simon K, Voiculescu M, Akdogan M, Mazur W, Reijnders JG, Verhey E, Hansen BE, Janssen HL; ARES Study Group. Adding pegylated interfe — View Citation

Marcellin P, Ahn SH, Ma X, Caruntu FA, Tak WY, Elkashab M, Chuang WL, Lim SG, Tabak F, Mehta R, Petersen J, Foster GR, Lou L, Martins EB, Dinh P, Lin L, Corsa A, Charuworn P, Subramanian GM, Reiser H, Reesink HW, Fung S, Strasser SI, Trinh H, Buti M, Gaet — View Citation

Xie Q, Zhou H, Bai X, Wu S, Chen JJ, Sheng J, Xie Y, Chen C, Chan HL, Zhao M. A randomized, open-label clinical study of combined pegylated interferon Alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B. Clin In — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects who achieve HBeAg seroconversion	The number of subjects with HBeAg seroconversion at week 96 will be measured	at 96 week
Secondary	Number of participants who achieve HBeAg seroconversion	The number of subjects with HBeAg seroconversion at week 48 and 72 will be measured	at 48 week;at 72 week
Secondary	The percentage decrease of HBsAg level at group A,B,C	The level of HBsAg in group A,B,C at week 48 ,72 and 96 will be measured,changing from baseline	at 48 week;at 72 week;at 96 week
Secondary	Number of participants who achieve HBeAg loss	The number of subjects with HBeAg loss at week48.72 and 96 will be measured	at 48 week;at 72 week;at 96 week
Secondary	The number of subjects who achieve HBVDNA undetectable	The number of subjects with HBVDNA undetectable at week 24,48,72 and 96 will be measured	at 24 week;48 week;at 72 week;at 96 week
Secondary	The factor such as HBsAg level related to responsible rate	The HBsAg level at week 48,72,96 will be measured, to assess whether the quantitative HBsAg level related to the responsible rate	at week 48,72,96
Secondary	The number of subjects who achieve ALT back to normal	The number of subjects with normal ALT at week 48,72 and 96 will be measured	at 48 week;at 72 week;at 96 week