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

NCT ID: NCT02474316

Last Updated: 2015-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

366 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-31

Study Completion Date

2017-12-31

Brief Summary

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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

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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

Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PegINF plus nucleos(i)de analgoue

Peginterferon alfa-2a 180μg /wk plus nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks

Group Type EXPERIMENTAL

Peginterferon alfa-2a

Intervention Type DRUG

Peginterferon alfa-2a 180ug/wk s.c for 48 weeks

nucleos(t)ide analgoue

Intervention Type DRUG

nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks

nucleos(t)ide analgoue

nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks

Group Type ACTIVE_COMPARATOR

nucleos(t)ide analgoue

Intervention Type DRUG

nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks

Interventions

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Peginterferon alfa-2a

Peginterferon alfa-2a 180ug/wk s.c for 48 weeks

Intervention Type DRUG

nucleos(t)ide analgoue

nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks

Intervention Type DRUG

Other Intervention Names

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Pegasys

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ruijin Hospital

OTHER

Sponsor Role lead

Responsible Party

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Qing XIe

Director of infectious disease

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Qing Xie

Role: STUDY_CHAIR

Ruijin Hospital

Locations

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The Third People's Hospital of Guilin

Guilin, , China

Site Status RECRUITING

Ruijin Hospital

Shanghai, , China

Site Status RECRUITING

Shanghai Public Health Clinical Center

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Qing Xie

Role: CONTACT

86-13651804273

Facility Contacts

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Shuquan Chen, doctor

Role: primary

Qing Xie, doctor

Role: primary

Wei Cai, doctor

Role: backup

Liang Chen, doctor

Role: primary

References

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Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003 Dec 20;362(9401):2089-94. doi: 10.1016/S0140-6736(03)15108-2.

Reference Type RESULT
PMID: 14697813 (View on PubMed)

Trepo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014 Dec 6;384(9959):2053-63. doi: 10.1016/S0140-6736(14)60220-8. Epub 2014 Jun 18.

Reference Type RESULT
PMID: 24954675 (View on PubMed)

Tassopoulos NC, Volpes R, Pastore G, Heathcote J, Buti M, Goldin RD, Hawley S, Barber J, Condreay L, Gray DF. Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group. Hepatology. 1999 Mar;29(3):889-96. doi: 10.1002/hep.510290321.

Reference Type RESULT
PMID: 10051494 (View on PubMed)

Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003 Feb 27;348(9):808-16. doi: 10.1056/NEJMoa020681.

Reference Type RESULT
PMID: 12606735 (View on PubMed)

Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carrilho FJ, Poordad F, Halota W, Horsmans Y, Tsai N, Zhang H, Tenney DJ, Tamez R, Iloeje U. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010 Feb;51(2):422-30. doi: 10.1002/hep.23327.

Reference Type RESULT
PMID: 20049753 (View on PubMed)

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 interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study). Hepatology. 2015 May;61(5):1512-22. doi: 10.1002/hep.27586. Epub 2015 Feb 27.

Reference Type RESULT
PMID: 25348661 (View on PubMed)

Other Identifiers

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HOPE

Identifier Type: -

Identifier Source: org_study_id