Combined Therapy With Peginterferon Alfa-2a With NA in NA-treated HBeAg Positive Patients

Phase 4

• Conditions: Chronic Hepatitis B
• Interventions: Drug: Peginterferon alfa-2a; Drug: nucleos(t)ide analgoue

• Registration Number: NCT02474316
• Lead Sponsor: Ruijin Hospital

Brief Summary

This is a prospective, randomized, multicenter, open-label study. After more than 24 weeks NA treatment, HBeAg positive CHB patients who achieved HBV DNA\<1000copies/ml but HBeAb negative, will be randomized (1:1) into 2 study arms as follows:

Arm A: Peginterferon alfa-2a 180μg /wk plus NA 1 piece qd for 48 weeks Arm B: Entecavir 0.5mg qd for 48 weeks

Detailed Description

This is a prospective, randomized, multicenter, open-label study. After more than 24 weeks NA treatment, HBeAg positive CHB patients who achieved HBV DNA\<1000copies/ml but HBeAb negative, will be randomized (1:1) into 2 study arms as follows:

Arm A: Peginterferon alfa-2a 180μg /wk plus NA 1piece qd for 48 weeks Arm B:NA 1 piece qd for 48 weeks

The primary endpoint: HBeAg seroconversion at week 48

Study Timeline

• Study Start: 2014-08
• Study First Submitted: 2015-03-25
• Status Verified: 2015-06
• Study First Submitted QC: 2015-06-12
• Study First Posted: 2015-06-17
• Last Update Submitted: 2015-12-02
• Last Update Posted: 2015-12-03
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 366

Inclusion Criteria

Not provided

Exclusion Criteria

1. Co-infection with active hepatitisA, hepatitisC, hepatitisD and/or human immunodeficiency virus (HIV)

2. AFP>50ng/ml and/or evidence of hepatocellular carcinoma

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

   1. Serum albumin <35 g/L;
   2. Prothrombine time prolonged≥ 4 seconds or PTA < 60%;
   3. Serum bilirubin > 34 µmol/L;
   4. History of encephalopathy;
   5. Ascites

4. 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)

5. Pregnant or breast-feeding Women

6. ANC<1.5x 10^9/L or PLT<90x 10^9/L

7. Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment

8. 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

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

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

11. History of chronic pulmonary disease associated with functional limitation

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

13. Hemodialysis patients or patients with renal insufficiency

14. History of a severe seizure disorder or current anticonvulsant use

15. 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

16. History of thyroid disease poorly controlled on prescribed medications

17. Evidence of severe retinopathy or clinically relevant ophthalmologic disorder

18. 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

19. Immunomodulatory treatment (including interferon) or LDT within 1 year prior to the first dose of treatment

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PegINF plus nucleos(i)de analgoue	Peginterferon alfa-2a	Peginterferon alfa-2a 180μg /wk plus nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks
PegINF plus nucleos(i)de analgoue	nucleos(t)ide analgoue	Peginterferon alfa-2a 180μg /wk plus nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks
nucleos(t)ide analgoue	nucleos(t)ide analgoue	nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks

Primary Outcome Measures

Name	Time	Method
Number of participants who achieve HBeAg seroconversion	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the HBeAg seroconversion in HBeAg positive CHB patients on treatment with Entecavir and with HBV DNA \<1000copies/ml which will be measured by the number of participants who achieve HBeAg seroconversion

Secondary Outcome Measures

Name	Time	Method
Number of participants who achieve combined response II (defined as HBeAg seroconversion and HBV DNA<1000copies/mL)	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the combined response II which will be measured by number of participants who achieve combined response II
Percentage of participants who achieve HBsAg <1000IU/mL	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the percentage of participants who achieve HBsAg\<1000IU/mL
Percentage of of participants who achieve HBsAg <100IU/mL	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the percentage of of participants who achieve HBsAg\<100IU/mL
Number of participants who achieve combined response I (defined as HBeAg seroconversion and HBV DNA<100000copies/mL)	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the combined response I which will be measured by number of participants who achieve combined response I
Number of participants who achieve HBeAg loss	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBeAg seroconversion which will be measured by number of participants who achieve HBeAg loss
Number of participants who achieve HBsAg loss	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg loss which will be measured by number of participants who achieve HBsAg loss
Number of participants who achieve HBsAg seroconversion	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg seroconversion which will be measured by number of participants who achieve HBsAg seroconversion
HBsAg decline from baseline	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg decline from baseline
Number of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<1000IU/mL)	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the dural response I which will be measured by number of participants who achieve dural response I
Number of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<100IU/mL)	at week 48	To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the dural response II which will be measured by number of participants who achieve dural response II
Number of Participants with AE	at week 48	Number of participants with adverse events as a measure of safety and tolerability
Number of Participants with SAE	at week 48	Number of participants with SAEs as a measure of safety and tolerability

Trial Locations

Locations (3)

The Third People's Hospital of Guilin; 🇨🇳 Guilin, China

Shanghai Public Health Clinical Center; 🇨🇳 Shanghai, China

Ruijin Hospital; 🇨🇳 Shanghai, China