Clinical trial NCT02474316: Combined Therapy With Peginterferon Alfa-2a With NA in NA-treated HBeAg Positive Patients
Official title: A Prospective, Randomized, Multicenter, Open-label Study Evaluating HBeAg Seroconversion in HBeAg Positive CHB Patients on Treatment With NA Switched to Combined Therapy With Peginterferon Alfa-2a and NA for 48 Weeks
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis B
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2015-06-17
Enrollment: 366
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: 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

Eligibility criteria: 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 before treated with Entecavir;
3. Treated with NA for more than 24 weeks and achieve HBV DNA\<1000copies/ml with HBeAb negative;
4. Women without ongoing pregnancy or breast feeding and willing to take an effective contraceptive measure during the treatment
5. Agree to participate in the study and sign the patient informed consent.

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

Primary outcomes:
measure: Number of participants who achieve HBeAg seroconversion
timeFrame: at week 48
Secondary outcomes:
measure: Number of participants who achieve HBeAg loss
timeFrame: at week 48
measure: Number of participants who achieve HBsAg loss
timeFrame: at week 48
measure: Number of participants who achieve HBsAg seroconversion
timeFrame: at week 48
measure: HBsAg decline from baseline
timeFrame: at week 48
measure: Percentage of participants who achieve HBsAg <1000IU/mL
timeFrame: at week 48
measure: Percentage of of participants who achieve HBsAg <100IU/mL
timeFrame: at week 48
measure: Number of participants who achieve combined response I (defined as HBeAg seroconversion and HBV DNA<100000copies/mL)
timeFrame: at week 48
measure: Number of participants who achieve combined response II (defined as HBeAg seroconversion and HBV DNA<1000copies/mL)
timeFrame: at week 48
measure: Number of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<1000IU/mL)
timeFrame: at week 48
measure: Number of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<100IU/mL)
timeFrame: at week 48
measure: Number of Participants with AE
timeFrame: at week 48
measure: Number of Participants with SAE
timeFrame: at week 48
Other outcomes:
Locations:
city: Guilin
country: China
facility: The Third People's Hospital of Guilin
city: Shanghai
country: China
facility: Ruijin Hospital
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
Study officials:
affiliation: Ruijin Hospital
name: Qing Xie
role: STUDY_CHAIR
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