A Study of Combination or Sequential Treatment With PEGASYS (Peginterferon Alfa-2a) and Entecavir in Patients With HBeAg Positive Chronic Hepatitis B

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00940485
First received: June 16, 2009
Last updated: February 26, 2016
Last verified: February 2016
  Purpose
This 2 arm study will assess the efficacy and safety of Pegasys in combination or sequential treatment with entecavir in patients with HBeAg positive chronic hepatitis B. Patients who have been pretreated with, and responded to, entecavir for 9 to 36 months were randomized to one of 2 groups, to receive Pegasys 180micrograms/week sc for 48 weeks + entecavir 0.5mg po daily for 8 weeks, or entecavir 0.5mg po daily for 48 weeks. The anticipated time on study treatment is 3-12 months.

Condition Intervention Phase
Hepatitis B, Chronic
Drug: entecavir
Drug: peginterferon alfa-2a [Pegasys]
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study on Optimizing HBeAg Seroconversion in HBeAg Positive CHB Patients With Combination or Sequential Treatment of Pegylated Interferon Alpha-2a and Entecavir

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Hepatitis B Envelope Antigen Seroconversion at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    Hepatitis B envelope Antigen (HBeAg) seroconversion was defined as the absence of HBeAg and the presence of antibody to Hepatitis B envelope antigen (anti-HBe).


Secondary Outcome Measures:
  • Percentage of Participants With Loss of Hepatitis B Envelope Antigen at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    Loss of Hepatitis B Envelope Antigen (HBeAg) is defined as the absence of HBeAg.

  • Percentage of Participants With Hepatitis B Virus - Deoxyribonucleic Acid <1000 Copies/ Millilitre at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    Blood was collected for Hepatitis B Virus - Deoxyribonucleic Acid (HBV -DNA) and was analysed at the central laboratories using the Roche approved polymerase chain reaction (PCR) methodology at Week 48. Percentage of participants with HBV-DNA < 1000 copies/mL was reported.

  • Percentage of Participants With Hepatitis B Surface Antigen Loss at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.

  • Percentage of Participants With Hepatitis B Surface Antigen Seroconversion at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    Hepatitis B Surface Antigen (HBsAg) seroconversion was defined as loss of HBsAg and presence of anti-HBs .(antibody to Hepatitis B surface antigen)

  • Percentage of Participants With Normalized Alanine Aminotransferase at Week 48 [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
    Normalized Alanine Aminotransferase (ALT) is defined as having a baseline ALT value > upper limit of normal (ULN), and a decrease in ALT value to ≤ ULN at the given time point.

  • Quantitative Change in Mean Hepatitis B Envelope Antigen Over Time [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Quantitative hepatitis B envelope antigen (HBeAg) results were analyzed in central lab. Values that were less than lower limit of quantification (LLOQ) had been replaced by LLOQ when analyzed, e.g. <1000 was replaced by 1000 and <0.2 was replaced by 0.2. Quantitative HBeAg value unit was calculated using 'Paul Ehrlich Institute units per millilitre' (PEIU/ml). Change in HBeAg was analysed at Weeks 0, 8, 12, 24, 36, and 48.

  • Quantitative Change in Mean Hepatitis B Surface Antigen Change Over Time [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Quantitative Hepatitis B Surface Antigen (HBsAg) results were analyzed in central lab. Values that were less than LLOQ had been replaced by LLOQ when analyzed, e.g. <1000 was replaced by 1000 and <0.2 was replaced by 0.2. Quantitative HBsAg calculated using 'International Units Per Millilitre' (IU/mL). Change in HBsAg was analysed at Weeks 0, 8, 12, 24, 36, and 48.

  • Number of Participants With Incidence of Adverse Events and Serious Adverse Events [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Events (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

  • Number of Participants With Laboratory Abnormalities Which Were Captured as an Adverse Event [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    Participants with clinically significant laboratory abnormalities which were captured as an AE (at the >=5% threshold) were presented.


Enrollment: 200
Study Start Date: April 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peginterferon alfa-2a + entecavir
Participants received PEGASYS® (peginterferon alfa-2a)180 micrograms (mcg) subcutaneously once weekly for 48 weeks, plus entecavir 0.5 milligram (mg) orally once daily for 8 weeks.
Drug: entecavir
0.5mg po daily for 8 weeks
Drug: peginterferon alfa-2a [Pegasys]
180 micrograms sc/week for 48 weeks
Active Comparator: Entecavir
Participants received entecavir 0.5 mg orally once daily for 48 weeks.
Drug: entecavir
0.5mg po daily for 48 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >=18 and </= 65 years of age
  • HBeAg positive chronic hepatitis B
  • Pre-treatment with entecavir for 9-36 months

Exclusion Criteria:

  • Antiviral, antineoplastic or immunomodulatory treatment
  • Co-infection with active hepatitis A, C or D, or HIV
  • Evidence of decompensated liver disease
  • History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00940485

Locations
China
Changsha, China, 410008
Chengdu, China, 610041
Fu Zhou, China, 350005
Guangzhou, China, 510515
Hangzhou, China, 310003
Wuhan, China, 430030
Xi'an, China, 710038
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00940485     History of Changes
Other Study ID Numbers: ML22265 
Study First Received: June 16, 2009
Results First Received: January 24, 2016
Last Updated: February 26, 2016
Health Authority: China: Ministry of Health

Additional relevant MeSH terms:
Hepatitis
Hepatitis B
Hepatitis B, Chronic
DNA Virus Infections
Digestive System Diseases
Hepadnaviridae Infections
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
Virus Diseases
Entecavir
Interferon-alpha
Peginterferon alfa-2a
Anti-Infective Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on April 27, 2016