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

NCT02474316 | Unknown Phase 4

• 1 other identifier: HOPE
• Study Type: interventional
• Target: 366
• Locations: 1 country
• Sites: 3

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

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Number of participants who achieve HBeAg seroconversion

  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

  at week 48

Secondary Outcomes (12)

• Number of participants who achieve HBeAg loss

  at week 48

• Number of participants who achieve HBsAg loss

  at week 48

• Number of participants who achieve HBsAg seroconversion

  at week 48

• HBsAg decline from baseline

  at week 48

• Percentage of participants who achieve HBsAg <1000IU/mL

  at week 48

Study Arms (2)

PegINF plus nucleos(i)de analgoue

EXPERIMENTAL

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

Drug: Peginterferon alfa-2a; Drug: nucleos(t)ide analgoue

nucleos(t)ide analgoue

ACTIVE COMPARATOR

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

Drug: nucleos(t)ide analgoue

Interventions

Peginterferon alfa-2a DRUG

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

Also known as: Pegasys

PegINF plus nucleos(i)de analgoue

nucleos(t)ide analgoue DRUG

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

PegINF plus nucleos(i)de analgoue; nucleos(t)ide analgoue

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients with age ≥18 and ≤65 years;
• 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;
• Treated with NA for more than 24 weeks and achieve HBV DNA\<1000copies/ml with HBeAb negative;
• Women without ongoing pregnancy or breast feeding and willing to take an effective contraceptive measure during the treatment
• Agree to participate in the study and sign the patient informed consent.

You may not qualify if:

• Co-infection with active hepatitisA, hepatitisC, hepatitisD and/or human immunodeficiency virus (HIV)
• AFP\>50ng/ml and/or evidence of hepatocellular carcinoma
• 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:
• Serum albumin \<35 g/L;
• Prothrombine time prolonged≥ 4 seconds or PTA \< 60%;
• Serum bilirubin \> 34 µmol/L;
• History of encephalopathy;
• Ascites
• 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)
• Pregnant or breast-feeding Women
• ANC\<1.5x 10\^9/L or PLT\<90x 10\^9/L
• Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment
• 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
• History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.)
• History of esophageal varices bleeding or other evidence of esophageal varices bleeding or other symptoms consistent with decompensated liver disease

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (3)

The Third People's Hospital of Guilin

Guilin, China

RECRUITING

Ruijin Hospital

Shanghai, China

RECRUITING

Shanghai Public Health Clinical Center

Shanghai, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 14697813 RESULT

• 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.

  PMID: 24954675 RESULT

• 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.

  PMID: 10051494 RESULT

• 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.

  PMID: 12606735 RESULT

• 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.

  PMID: 20049753 RESULT

• 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.

  PMID: 25348661 RESULT

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Qing Xie

  Ruijin Hospital

  STUDY CHAIR

Central Study Contacts

Qing Xie

CONTACT

86-13651804273; xieqingrjh2015@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of infectious disease

Study Record Dates

• First Submitted: March 25, 2015
• First Posted: June 17, 2015
• Study Start: August 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: December 3, 2015

Record last verified: 2015-06

Locations

CN (3)