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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02263079
Registration number
NCT02263079
Ethics application status
Date submitted
2/10/2014
Date registered
13/10/2014
Date last updated
24/08/2020
Titles & IDs
Public title
A Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Group in Children With Hepatitis B Envelope Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) in the Immune-Tolerant Phase
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Scientific title
A Phase IIIb, Randomized, Open-Label Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Patients in Children With HBeAg Positive Chronic Hepatitis B in the Immune-Tolerant Phase
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Secondary ID [1]
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2006-000977-31
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Secondary ID [2]
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NV25361
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Pediatric Immuno-Tolerant Chronic Hepatitis B
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Condition category
Condition code
Infection
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Other infectious diseases
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Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Entecavir
Treatment: Drugs - Lamivudine
Treatment: Drugs - Pegylated Interferon Alfa-2A
Experimental: Peg-IFN-Alfa-2A + Lamivudine or Entecavir - Participants will receive lamivudine or entecavir alone for 8 weeks followed by peg-IFN-alfa-2A in combination with lamivudine or entecavir for 48 weeks.
No Intervention: Untreated Control Participants - Untreated control participants will be observed up to 80 weeks.
Experimental: Peg-INF-Alfa-2A Monotherapy - Participants will receive Peginterferon Alfa 2A subcutaneously once weekly with dosing based on body surface area (BSA) categories for 48 weeks.
Treatment: Drugs: Entecavir
Participants will receive entecavir, either as a film-coated tablet or oral solution, once daily at a dose of 0.015 milligrams per kilogram (mg/kg) (maximum daily dose of 0.5 mg).
Treatment: Drugs: Lamivudine
Participants will receive lamivudine, either as a film-coated tablet or oral solution, once daily at a dose of 3 mg/kg (maximum daily dose of 100 mg).
Treatment: Drugs: Pegylated Interferon Alfa-2A
Participants will receive pegylated interferon-alfa-2A at a body surface area (BSA) based dose of 180 micrograms per 1.73 square meter (mcg/1.73m^2) BSA.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation
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Assessment method [1]
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This endpoint is defined as loss of HBsAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80). The percentage of responders (response rate) and 95% CI (using the Clopper-Pearson method) for the response rate are presented for each group.
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Timepoint [1]
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24 weeks post-treatment/at the end of untreated observation (Week 80)
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Secondary outcome [1]
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Percentage of Participants With Loss of HBsAg
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Assessment method [1]
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This endpoint is defined as loss of HBsAg at 1 year post-treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
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Timepoint [1]
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1 year post-end of treatment (End of treatment = Week 56)
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Secondary outcome [2]
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Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)
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Assessment method [2]
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This endpoint is defined as loss of HBeAg at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
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Timepoint [2]
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24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
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Secondary outcome [3]
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Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs
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Assessment method [3]
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This endpoint measures the seroconversion to anti-HBs defined as loss of HBsAg and presence of anti-HBs at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
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Timepoint [3]
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24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
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Secondary outcome [4]
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Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe
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Assessment method [4]
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This endpoint measures the seroconversion to anti-HBe defined as loss of HBeAg and presence of anti-HBe at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
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Timepoint [4]
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24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
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Secondary outcome [5]
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Percentage of Participants With Different Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels (Less Than [<] 20,000 International Units Per Milliliter [IU/mL], < 2000 IU/mL, or Undetectable HBV DNA)
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Assessment method [5]
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This endpoint measures different HBV DNA levels (<20000 IU/mL, <2000 IU/mL and undetectable) measured by PCR or hybridization at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-treatment in the treated group. HBV-DNA undetectable is defined as <29 IU/mL. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
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Timepoint [5]
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24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
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Secondary outcome [6]
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Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm
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Assessment method [6]
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This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Peg-INF-Alfa-2A + Lamivudine or Entecavir arm.
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Timepoint [6]
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Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24
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Secondary outcome [7]
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Change From Baseline in HBV DNA Levels in the Untreated Control Participants
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Assessment method [7]
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This outcome measure presents HBV DNA levels measured at defined time points from baseline in the Untreated Control arm.
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Timepoint [7]
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Baseline, Week 32, 56 and end of untreated observation (Week 80)
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Secondary outcome [8]
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Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <20,000 IU/mL
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Assessment method [8]
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This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels <20,000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
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Timepoint [8]
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24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
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Secondary outcome [9]
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Percentage of Participants With Combined Response for HBeAg Seroconversion (Defined as Loss of HBeAg and Presence of Anti-HBe) and HBV DNA Levels <2000 IU/mL
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Assessment method [9]
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This endpoint measures the combined response for HBeAg Seroconversion and HBV DNA Levels <2000 IU/mL at 24 weeks post-treatment (follow-up Week 24)/end of untreated observation (Week 80) and at 1 year post-end of treatment in the treated group. The HBeAg is defined as loss of HBeAg and presence of anti-HBe. The 95% Confidence Interval of response rate is calculated by Clopper-Pearson method.
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Timepoint [9]
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24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
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Secondary outcome [10]
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Percentage of Participants With Adverse Events (AEs)
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Assessment method [10]
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An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
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Timepoint [10]
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Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80)
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Secondary outcome [11]
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Percentage of Participants With AEs Leading to Dose Modification or Interruption
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Assessment method [11]
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This endpoint measures AEs and lab abnormalities leading to dose interruption or dose modification. Does modification included dose reduced, dose increased or drug interrupted. Adverse events included laboratory abnormalities reported as adverse events.
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Timepoint [11]
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Baseline up to 24 weeks post-end of treatment
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Secondary outcome [12]
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Serum Concentration of Peg-INF-Alfa-2A
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Assessment method [12]
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The serum concentration of Peg-INF-Alfa-2A was measured in picogram/milliliter.
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Timepoint [12]
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At Weeks 12, 16, 20, 32, 44, 56
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Eligibility
Key inclusion criteria
- Positive for HBsAg and HBeAg for more than 6 months prior to baseline
- Detectable HBV-DNA (>20,000 IU/mL) as measured by polymerization chain reaction (PCR)
or hybridization on at least 2 occasions at least one month apart with the latest
determination obtained less than or equal to (</=) 42 days prior to baseline
- Compensated liver disease (Child-Pugh Class A clinical classification)
- Either Liver biopsy performed within 2 years prior to baseline showing no or minimal
fibrosis (Liver Biopsy Scores and stable normal ALT levels (less than or equal to
upper limit of normal [ULN]) during the 6 months leading up to baseline (including two
separate occasions at least 1 month apart over the 6 months prior to baseline).
Screening ALT levels must be normal (</= ULN) OR Stable normal ALT levels (</= ULN),
during the 1 year leading up to baseline (including three separate occasions at least
1 month apart over the 1 year prior to baseline) and no signs of hepatocellular
carcinoma (HCC), advanced fibrosis/cirrhosis, or splenomegaly on liver abdominal
ultrasound at screening. Screening ALT levels must be normal (</= ULN)
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Minimum age
3
Years
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Maximum age
17
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Participants who have received investigational drugs or licensed treatments with anti
HBV activity (Exception: Participants who have had a limited [</= 7-day] course of
acyclovir for herpetic lesions more than 1 month before the study baseline visit are
not excluded)
- Participants who have participated in any other clinical trial or who have received
any investigational drug within 6 months prior to baseline
- Known hypersensitivity to interferon (IFN), pegylated interferon-alfa-2a or lamivudine
or entecavir
- Positive test results at screening for hepatitis A virus Immunoglobulin M (IgM)
antibody (Ab), anti-hepatitis C virus (HCV) Ab, anti- hepatitis D (HDV) Ab or
anti-human immunodeficiency virus (HIV) Ab
- Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or
clinical evidence such as ascites or varices)
- Advanced fibrosis or cirrhosis
- Suspicion of HCC on liver abdominal ultrasound (all patients to have liver abdominal
ultrasound within 6 months prior to baseline)
- History or other evidence of a medical condition associated with chronic liver disease
other than CHB including metabolic liver diseases such as hemochromatosis, Wilson's
disease or alpha-1 anti-trypsin deficiency
- Active substance abuse within 6 months prior to screening
- Sexually active females of childbearing potential and sexually active males who are
not willing to utilize reliable contraception during treatment and for 90 days
following the end of treatment
- Females who are pregnant or who are breastfeeding (females of childbearing potential
who have a positive urine or serum pregnancy test result within 24 hours of baseline
are excluded)
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
16/06/2014
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
29/01/2020
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Sample size
Target
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Accrual to date
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Final
62
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Recruitment in Australia
Recruitment state(s)
SA
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Recruitment hospital [1]
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Womens and Childrens Hospital; Department of Gastroenterology - North Adelaide
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Recruitment postcode(s) [1]
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5006 - North Adelaide
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Recruitment outside Australia
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United States of America
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Missouri
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United States of America
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New York
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United States of America
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Pennsylvania
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Belgium
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Bruxelles
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Belgium
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Gent
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Germany
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Essen
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Germany
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Mainz
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Germany
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München
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Germany
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Wuppertal
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Italy
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Emilia-Romagna
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Malaysia
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Kuala Lumpur
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Romania
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Bucharest
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Russian Federation
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Saint Petersburg
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Russian Federation
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Samara
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Taiwan
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Taoyuan County
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Turkey
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Adana
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Turkey
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Ankara
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Ukraine
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Kyiv
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United Kingdom
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Birmingham
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United Kingdom
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Leeds
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United Kingdom
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London
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United Kingdom
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State/province [22]
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Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This randomized, controlled, parallel group, open-label multicenter study will evaluate the
efficacy and safety of a combination of pegylated interferon alfa-2A (Pegasys) plus
lamivudine or entecavir compared with an untreated control group in participants with HBeAg
positive CHB in the immune tolerant phase. NOTE: STUDY RECRUITMENT HAS BEEN TERMINATED
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02263079
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Clinical Trials
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Address
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Hoffmann-La Roche
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Fax
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Email
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02263079
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