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Trial registered on ANZCTR


Registration number
ACTRN12610001101077
Ethics application status
Approved
Date submitted
5/11/2010
Date registered
16/12/2010
Date last updated
14/03/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
The Evaluation of efficacy and safety of Tenofovir in combination with peginterferon alpha-2a subcutaneous for 48 weeks in patients with chronic hepatitis B viral infections (HBV)
Scientific title
A randomized, open-label, controlled, multi-centre pilot study evaluating the efficacy and safety of Tenofovir 300 mg PO in combination with peginterferon alpha-2a subcutaneous 180 micrograms for 48 weeks in patients with HBeAg-positive CHB
Secondary ID [1] 252894 0
Study No SAR020506
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B viral infection 258424 0
Condition category
Condition code
Infection 258591 258591 0 0
Other infectious diseases
Oral and Gastrointestinal 258738 258738 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 258739 258739 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1 Oral antiviral Tenofovir 300mg (daily for 48weeks) plus Peginterferon 180micrograms (subcutaneous injection once weekly for 48 weeks)
Arm 2 Peginterferon 180micrograms (subcutaneous injection once weekly for 24weeks) followed by combination Oral antiviral Tenofovir 300mg (daily for 24weeks) plus Peginterferon 180micrograms (subcutaneous injection once weekly for 24 weeks)
Arm 3 Peginterferon monotherapy 180micrograms (subcutaneous injection once weekly for 48weeks)
Intervention code [1] 257422 0
Treatment: Drugs
Comparator / control treatment
Peginterferon alpha-2a 180micrograms (subcutaneous injection once weekly for 48weeks)
Control group
Active

Outcomes
Primary outcome [1] 259439 0
The primary objective of this study is to demonstrate the efficacy of the combination of peginterferon alpha-2a with Tenofovir in achieving sustained HBV suppression as measured by HBsAg loss in adult patients with HBeAg positive CHB by serum assay (blood test)
Timepoint [1] 259439 0
24weeks post dosing of study medication.
Secondary outcome [1] 265987 0
Evaluating the effect of the combination of peginterferon alpha-2a with Tenofovir on HBsAg clearance rates by a lead in phase of Peginterferon monotherapy for 24 weeks prior to combination therapy by serum assay (blood test)
Timepoint [1] 265987 0
24weeks post dosing of study medication.
Secondary outcome [2] 265988 0
Evaluating the effect of peginterferon and Tenofovir combination therapy on other parameters of viral suppression including; HBV DNA non-detectability, reduction from baseline, and sustained reduction in HBV DNA over the course of the study. HBeAg loss, HBeAb seroconversion and reduction in HBeAg titres from baseline HBsAg loss, HBsAb seroconversion and reduction in HBsAg titres from baseline and ALT normalization by serum assay (blood test)
Timepoint [2] 265988 0
24weeks post dosing of study medication.

Eligibility
Key inclusion criteria
Documented Chronic Hepatitis B defined by all of the following:
1.Clinical history compatible with CHB
2.Detectable serum HBsAg at the Screening visit and at least 6 months prior
3.HBeAg-positive and HBeAb-negative at the Screening visit
4.History of evidence of chronic liver inflammation, documented by previous history of elevated serum ALT (at least two documented elevated ALT values spanning six months or more))
5.Elevated serum ALT level (1.1 – 10 x upper limit of normal (ULN)) at the Screening visit
6.Serum HBV DNA level = 3 log10 IU/mL at the screening visit
7.Chronic liver inflammation on a liver biopsy performed within the previous 5 years
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures
2.Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or Human immunodeficiency virus (HIV).
3.Has had any of the following drug therapy:
*Received nucleoside or nucleotide therapy whether approved or investigational in the three months before screening for this study.
*Received conventional interferon alpha or other immunomodulatory therapies in the six months before screening for this study.
*Has previously received Pegylated Interferon alpha at any stage for the treatment of CHB
4.Has a medical condition that requires frequent or prolonged use of systemic corticosteroids although inhaled or intra-articular corticosteroids are allowed.
5.Has a medical condition requiring the chronic or prolonged use of potentially hepatotoxic drugs or nephrotoxic drugs.
6.Is currently abusing alcohol or illicit drugs or has a history of alcohol abuse or illicit substance abuse within the preceding 12 months.

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)
The investigators will ensure that only patients who meet the inclusion and exclusion criteria will be considered eligible for the study.
This is an investigator initiated, randomized, open-label, national, multicenter, three-arm, pilot study evaluating the efficacy of peginterferon alpha-2a plus Tenofovir combination therapy and Peginterferon lead in therapy followed by combination therapy with Tenofovir in adult HBeAg-positive outpatients with CHB.
Only subjects who have provided written informed consent will be enrolled in the study.
allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration. Concealment is done by sealed envelopes. Central randomisation is done by fac from the offsite central administration. Randomisation has been developed by the statistician and concealed by sealed envelopes. Each randomisation will take the next sequential envelope allocated to the sites allocated concealed sealed envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e., computerised sequence)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/01/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 258010 0
Self funded/Unfunded
Name [1] 258010 0
Country [1] 258010 0
Australia
Primary sponsor type
Individual
Name
Dr Anouk Dev
Address
Dept of Gastroenterology
Level 3, Main Building
Monash Medical Centre
246 Clayton Road
Clayton Victoria
3168
Country
Australia
Secondary sponsor category [1] 257203 0
Individual
Name [1] 257203 0
Dr. Sally Bell
Address [1] 257203 0
35 Victoria Parade
Fitzroy 3065 Victoria
Country [1] 257203 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260004 0
Southern Health Human Research and Ethics Committee
Ethics committee address [1] 260004 0
Level 4, Main Building
Monash Medical Centre
246 Clayton Road
Clayton Victoria 3168
Ethics committee country [1] 260004 0
Australia
Date submitted for ethics approval [1] 260004 0
21/07/2010
Approval date [1] 260004 0
10/03/2011
Ethics approval number [1] 260004 0
HREC/10/SHA/17 - 10213A

Summary
Brief summary
This is a randomized, openlabel, national, multicenter, three arm, pilot, investigator initiated study evaluating the
efficacy and safety of Tenofovir 300 mg PO in combination with peginterferon alpha2a sc 180 µg in patients with
HBeAg positive CHB. The patients will be randomized into three treatment arms at a ratio of 1:1:1
Arm 1: Full course combination therapy: 48 weeks of both peginterferon alpha2a plus Tenofovir disoproxil fumarate
Arm 2: Peginterferon alpha2a lead-in therapy: 24 weeks of a ‘lead in’ course of peginterferon monotherapy, followed by 24 weeks of combination peginterferon
Arm 3: Peginterferon alpha2a 180mcg weekly for 48 weeks
The study consists of four periods:
Screening (= 8 weeks prior to Baseline visit),
Baseline Visit (Day 1),
Treatment Phase (48 weeks)
Posttreatment
Followup
(24 weeks)

Study purpose: The primary purpose of this study is to evaluate whether the combination of Peginterferon and Tenofovir therapy may lead to improved antiviral outcomes compared to that typically seen with Peginterferon monotherapy.

Objectives: The primary objective of this study is to demonstrate the efficacy of the combination of peginterferon alpha-2a with Tenofovir in achieving sustained HBV suppression as measured by HBsAg loss in adult patients with HBeAg positive CHB

Secondary objectives include
1. Evaluating the effect of on HBsAg clearance rates by a lead in phase of Peginterferon monotherapy for 24 weeks prior to combination therapy
2. Evaluating the effect of peginterferon and Tenofovir combination therapy on other parameters of viral suppression including
3. HBV DNA non-detectability, reduction from baseline, and sustained reduction in HBV DNA over the course of the study.
4. HBeAg loss, Anti-HBe seroconversion and reduction in HBeAg titres from baseline
5. HBsAg loss, HBsAb seroconversion and reduction in HBsAg titres from baseline
6. ALT normalization
7. To determine which baseline and ‘on therapy’ markers may be used to predict clinical and virological outcomes including quantitative HBeAg and HBsAg titres, HBV viral load, ALT and HBV genotype

In addition a sub Immunological Study will be conducted at 2 of the study sites (Monash Medical Centre and St
Vincent’s Hospital Melbourne). Patients recruited at both sites will be invited to participate in smaller subcohort
study evaluating innate immune during the treatment and follow up periods to determine whether innate immune function can be used as a predictive marker of treatment induced HBsAg and HBeAg seroconversion.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31789 0
Address 31789 0
Country 31789 0
Phone 31789 0
Fax 31789 0
Email 31789 0
Contact person for public queries
Name 15036 0
Dr. Dilip Ratnam
Address 15036 0
Department of Gastroenterology
Level 3, Main Building
Monash Medical Centre
246 Clayton Road, Clayton Victoria
3168
Country 15036 0
Australia
Phone 15036 0
613 9594 3177
Fax 15036 0
613 9594 6586
Email 15036 0
[email protected]
Contact person for scientific queries
Name 5964 0
Dr. Dilip Ratnam
Address 5964 0
Department of Gastroenterology
Level 3, Main Building
Monash Medical Centre
246 Clayton Road, Clayton Victoria
3168
Country 5964 0
Australia
Phone 5964 0
613 9594 3177
Fax 5964 0
613 9594 6586
Email 5964 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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