A Real-World Study of Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B

Chronic Hepatitis B Clinical Trial

— COST  

Official title:

A Real-World Study of Sequential Combination Therapy With Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03357822
• Other study ID #: COST study
• Status: Recruiting
• Phase: Phase 4
• First received: November 20, 2017
• Last updated: April 23, 2018
• Start date: January 25, 2018
• Est. completion date: July 25, 2022

Study information

• Verified date: April 2018
• Source: Tongji Hospital
• Contact: Qin Ning
• Phone: 86 27 83662391
• Email: qning[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the prospective real-world study is to evaluate whether sequential combination therapy with pegylated interferon plus entecavir/tenofovir could induce higher rates of HBsAg loss in nucleoside-treated patients with chronic hepatitis B compared to continuous nucleoside treatment.

Description:

Patents who were treated with NA at least one year and achieved hepatitis B virus (HBV) DNA suppression and HBsAg level<3000 international unit (IU) /mL are enrolled in this study, they are assigned into two groups, in group I, patients will receive pegylated interferon plus entecavir/tenofovir for 48/72/96 weeks, in group II, patients will receive entecavir/tenofovir for 96 weeks. HBsAg loss rates at the end of treatment and sustained response at the end of follow up will be evaluated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: July 25, 2022
• Est. primary completion date: January 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male and female patients from 18 to 65 years of age;

2. HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history;

3. Before nucleotides or nucleosides treatment, ALT > 2 upper limit of normal value (ULN), HBV DNA >10000 copies/ml, HBsAg positive;

4. Serum HBV DNA = 500 copies/ml;

5. HBsAg<3000 IU/ml;

6. HBsAg positive;

7. Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug;

8. Absence of cirrhosis confirmed by ultrasonic test;

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

Exclusion Criteria:

1. HBV DNA > 500 copies/ml;

2. Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;

3. Women with ongoing pregnancy or breast-feeding;

4. Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);

5. ALT >10 ULN;

6. Evidence of decompensated liver disease (Child-Pugh score > 5). Child-Pugh > 5 means, if one of the following 5 conditions are met, the patient has to be excluded:

7. one of the following 5 conditions are met, the patient has to be excluded:

8. Serum albumin < 3.5 g/L;

9. Prothrombin time > 3 seconds prolonged;

10. Serum bilirubin > 34 µ mol/L;

11. History of encephalopathy;

12. History of variceal bleeding;

13. Ascites;

14. 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);

15. Signs or symptoms of hepatocellular carcinoma, patients with a value of alpha-fetoprotein > 100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. Patients with values < 20 ng/mL but > 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liver imaging;

16. Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;

17. Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;

18. Serum creatinine level > 1.5 ULN in screening period.

19. Phosphorus < 0.65 mmol/L;

20. antinuclear antibody (ANA) > 1:100;

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

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

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

24. History of chronic pulmonary disease associated with functional limitation;

25. Diseases that interferon and nucleotides or nucleosides are not suitable.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Pegylated interferon
180ug Pegylated interferon is injected subcutaneously once a week
• Entecavir
0.5mg entecavir is orally taken every day
• Tenofovir disoproxil fumarate
300mg tenofovir is orally taken every day

Locations

Country	Name	City	State
China	302 Military Hospital of China	Beijing	Beijing
China	BeiJing YouAn Hospital, Capital Medical University	Beijing	Beijing
China	Departmen of infectious disease, Xiangya Hospital, Central-south Universit	Changsha	Hunan
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The First Hospital Affiliated to AMU	Chongqing	Chongqing
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing	Jiangsu
China	The Second Hospital of Nanjing	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Traditional Chinese Medicine,Xiamen Hospital	Shantou	Xiamen
China	The first affiliated hospital of Wenzhou medical universtiy	Wenzhou	Zhejiang
China	The First Affiliated Hospital of College of Medicine, Zhejiang University	Zhejiang	Hangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Tongji Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBsAg loss rate	Percentages of patients who achieve HBsAg loss at week 48	at week 48
Secondary	HBsAg loss rate	Percentages of patients who achieve HBsAg loss at week 72	at week 72
Secondary	HBsAg loss rate	Percentages of patients who achieve HBsAg loss at week 96	at week 96
Secondary	HBsAg level	Dynamic change in HBsAg level from baseline to week 48	at week 48
Secondary	HBsAg level	Dynamic change in HBsAg level from baseline to week 72	at week 72
Secondary	HBsAg level	Dynamic change in HBsAg level from baseline to week 96	at week 96
Secondary	sustained HBsAg loss rate	Percentages of patients who achieve HBsAg loss at week 120	at week 120
Secondary	decline in HBsAg level	Decline in HBsAg level from baseline to week 48	at week 48
Secondary	decline in HBsAg level	Decline in HBsAg level from baseline to week 72	at week 72
Secondary	decline in HBsAg level	Decline in HBsAg level from baseline to week 96	at week 96
Secondary	HBsAb appearance rate	Percentages of HBsAb appearance at week 48	at week 48
Secondary	HBsAb appearance rate	Percentages of HBsAb appearance at week 72	at week 72
Secondary	HBsAb appearance rate	Percentages of HBsAb appearance at week 96	at week 96
Secondary	HBsAb seroconversion rate	Percentages of HBsAb seroconversion at week 48	at week 48
Secondary	HBsAb seroconversion rate	Percentages of HBsAb seroconversion at week 72	at week 72
Secondary	HBsAb seroconversion rate	Percentages of HBsAb seroconversion at week 96	at week 96
Secondary	HBeAg loss rate	Percentages of HBeAg loss in the HBeAg-positive patients at week 48	at week 48
Secondary	HBeAg loss rate	Percentages of HBeAg loss in the HBeAg-positive patients at week 72	at week 72
Secondary	HBeAg loss rate	Percentages of HBeAg loss in the HBeAg-positive patients at week 96	at week 96
Secondary	HBeAg seroconversion rate	Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 48	at week 48
Secondary	HBeAg seroconversion rate	Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 72	at week 72
Secondary	HBeAg seroconversion rate	Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 96	at week 96
Secondary	Rate of HBV DNA level <1000 copies/mL	Percentages of HBV DNA level <1000 copies/mL at week 96	at week 96
Secondary	Rate of alanine aminotransferase (ALT) normalization	Percentages of ALT normalization at week 96	at week 96
Secondary	The rate of progression to cirrhosis	The rate of progression to cirrhosis at week 120	at week 120
Secondary	The incidence rate of hepatocarcinoma	The incidence rate of hepatocarcinoma at week 120	at week 120