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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
Secondary ID [1] 0 0
2006-000977-31
Secondary ID [2] 0 0
NV25361
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pediatric Immuno-Tolerant Chronic Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Loss of Hepatitis B Surface Antigen (HBsAg) at 24 Weeks Post-End of Treatment/End of Untreated Observation
Timepoint [1] 0 0
24 weeks post-treatment/at the end of untreated observation (Week 80)
Secondary outcome [1] 0 0
Percentage of Participants With Loss of HBsAg
Timepoint [1] 0 0
1 year post-end of treatment (End of treatment = Week 56)
Secondary outcome [2] 0 0
Percentage of Participants With Loss of Hepatitis B Virus Envelope Antigen (HBeAg)
Timepoint [2] 0 0
24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Secondary outcome [3] 0 0
Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs), Defined as Loss of HBsAg and Presence of Anti-HBs
Timepoint [3] 0 0
24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Secondary outcome [4] 0 0
Percentage of Participants With Seroconversion to Hepatitis B Envelope Antibody (Anti-HBe), Defined as Loss of HBeAg and Presence of Anti-HBe
Timepoint [4] 0 0
24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Secondary outcome [5] 0 0
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)
Timepoint [5] 0 0
24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Secondary outcome [6] 0 0
Change From Baseline in HBV DNA Levels in the Peg-INF-Alfa-2A (Treated) Arm
Timepoint [6] 0 0
Baseline, Week 8, 20, 32, 44, 56, Follow up Week 4 and 24
Secondary outcome [7] 0 0
Change From Baseline in HBV DNA Levels in the Untreated Control Participants
Timepoint [7] 0 0
Baseline, Week 32, 56 and end of untreated observation (Week 80)
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
24 weeks post-treatment /end of untreated observation (Week 80), and 1 year post-end of treatment (End of treatment = Week 56)
Secondary outcome [10] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [10] 0 0
Baseline up to 24 weeks post-treatment/end of untreated observation (Week 80)
Secondary outcome [11] 0 0
Percentage of Participants With AEs Leading to Dose Modification or Interruption
Timepoint [11] 0 0
Baseline up to 24 weeks post-end of treatment
Secondary outcome [12] 0 0
Serum Concentration of Peg-INF-Alfa-2A
Timepoint [12] 0 0
At Weeks 12, 16, 20, 32, 44, 56

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)
Minimum age
3 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/01/2020
Sample size
Target
Accrual to date
Final
62
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Womens and Childrens Hospital; Department of Gastroenterology - North Adelaide
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Missouri
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
Belgium
State/province [4] 0 0
Bruxelles
Country [5] 0 0
Belgium
State/province [5] 0 0
Gent
Country [6] 0 0
Germany
State/province [6] 0 0
Essen
Country [7] 0 0
Germany
State/province [7] 0 0
Mainz
Country [8] 0 0
Germany
State/province [8] 0 0
München
Country [9] 0 0
Germany
State/province [9] 0 0
Wuppertal
Country [10] 0 0
Italy
State/province [10] 0 0
Emilia-Romagna
Country [11] 0 0
Malaysia
State/province [11] 0 0
Kuala Lumpur
Country [12] 0 0
Romania
State/province [12] 0 0
Bucharest
Country [13] 0 0
Russian Federation
State/province [13] 0 0
Saint Petersburg
Country [14] 0 0
Russian Federation
State/province [14] 0 0
Samara
Country [15] 0 0
Taiwan
State/province [15] 0 0
Taoyuan County
Country [16] 0 0
Turkey
State/province [16] 0 0
Adana
Country [17] 0 0
Turkey
State/province [17] 0 0
Ankara
Country [18] 0 0
Ukraine
State/province [18] 0 0
Kyiv
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Birmingham
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Leeds
Country [21] 0 0
United Kingdom
State/province [21] 0 0
London
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

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
Trial website
https://clinicaltrials.gov/study/NCT02263079
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02263079