HBsAg Related Response Guided Therapy (S-RGT)

A Multi Center, Phase IIIb Study to Evaluate the Efficacy of Response Guided Therapy Using Quantitative HBsAg Measurement in Patient With HBeAg Positive Chronic Hepatitis B:

Primary objective: Compare Pegasys RGT overall response rate (i.e., HBeAg seroconversion rate) with Pegasys mono historical response rate at week 72 (48 week treatment with 24 week follow up)

Secondary objective :

• The changes of HBsAg titer

  • The rate of combined HBeAg seroconversion and HBV DNA < 300 copies/mL

    • The rate of serum HBV DNA < 300 copies/mL ⅳ. The rate of ALT normalization

      • The rate of HBsAg loss ⅵ. The rate of serum HBV DNA < 10,000 copies/mL

Study Overview

• Status: Unknown
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Peginterferon alfa-2a; Drug: Entecavir

Detailed Description

After 12w treatment of Pegasys, depends on results of quantitative HBsAg test, Patients will be allocated to one of three groups.

• HBsAg >20,000 : study termination
• Group A :1,500<HBsAg≤ 20,000
• Group B : .HBsAg ≤ 1500 At week 48, according to HbeAg seroconversion, patients will be allocated to one of two sub-groups(A-1, A-2, B-1, B-2) Patients are seen for evaluation at treatment weeks 4,8,12,24,36,48. Post-treatment assessments will be performed at 4,12 and 24 week during off-treatment phase for the assessment of the primary and main secondary endpoints of the study.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kwansik Lee, professor; Phone Number: +82 11 9636 9935; Email: leeks519@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120742
    • Recruiting
    • Shinchon Severance Hospital
    • Contact: Sanghoon Ahn, professor; Phone Number: 82-2-2228-1936; Email: ahnsh@yuhs.ac
    • Principal Investigator: Sanhoon Ahn, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Positive HBsAg for more than 6 months, positive HBeAg, detectable HBV DNA(patients must have > 100,000 copies/ml as measured by PCR) and anti-HBs negative
3. Elevated serum ALT > 2ULN but ≤ 10 × ULN as determined by two abnormal values taken ≥ 14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained ≤ 35 days prior to the first dose.

Exclusion Criteria:

1. Patients must not have received antiviral therapy for their chronic hepatitis B. Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded. Exception: patients who have had less than 6 months treatment of NA(Nucleos(t)ide analog) and more than 1 year wash-out period for systemic antiviral therapy and negative results in the NA resistance test at baseline are not excluded.
2. Positive test at screening for HAV IgM Ab, HCV-RNA or HCV Ab, HDV Ab or HIV Ab.
3. Diagnosed hepatic cellular carcinoma
4. Any evidence of decompensated liver disease (Childs B-C)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: HBsAg quantification>20,000 IU/ml; stop peginterferon alfa 2a if patients reach HBsAg quantification>20,000 Iu/ml at 12w	Drug: Peginterferon alfa-2a; Duration and combination; Other Names: Pegasys
Sham Comparator: HBsAg<=1500IU/ml; extend peginterferon alfa 2a until 48weeks	Drug: Peginterferon alfa-2a; Duration and combination; Other Names: Pegasys
Sham Comparator: HBsAg >1500 <=20,000 IU/ML; add Entecavir for 12w with peginterferon alfa 2a then, extend peginterferon alfa 2a until 48w	Drug: Peginterferon alfa-2a; Duration and combination; Other Names: Pegasys; Drug: Entecavir; combination; Other Names: Baraclude Tab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HBeAg seroconversion	24 weeks post treatment follow up

Secondary Outcome Measures

Outcome Measure	Time Frame
The changes of HBsAg titer	baseline and 24weeks post treatment follow up

Collaborators and Investigators

• Sponsor: Gangnam Severance Hospital
• Collaborators: Roche Pharma AG
• Investigators: Study Chair: Kwansik Lee, professor, Gangnam Severance Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): August 1, 2016

Study Registration Dates

• First Submitted: October 15, 2011
• First Submitted That Met QC Criteria: October 19, 2011
• First Posted (Estimate): October 20, 2011

Study Record Updates

• Last Update Posted (Estimate): October 31, 2012
• Last Update Submitted That Met QC Criteria: October 29, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Entecavir; Chronic Hepatitis B; Peginterferon alfa 2a; Response Guided Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2a; Entecavir
• Other Study ID Numbers: ML25588