The primary objective of this study is to demonstrate the superior antiviral efficacy of the combination of peginterferon alpha-2a plus telbivudine vs peginterferon alpha-2a monotherapy as demonstrated by HBV DNA non-detectability using the COBAS…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable of this study is the proportion of patients who
will achieve HBV DNA non-detectability by PCR at Week 52.
The proportion of patients (response rate) who will achieve HBV DNA
non-detectability at Week 52 and ALT normalization after 52 weeks* treatment
will be tested using the CMH test, stratified by country and/or baseline HBV
DNA level. The ratio of the response rates and the difference of the response
rates for combination therapy vs. peginterferon alfa-2a monotherapy will be
provided along with a 95% confidence interval.
Secondary outcome
The proportion of patients (response rate) who will achieve HBV DNA
non-detectability at Week 52 and ALT normalization after 52 weeks* treatment
will be tested using the CMH test.
Background summary
Overall, treatment of CHB is suboptimal and remains an area of unmet medical
need where better therapeutics and treatment strategies are needed. Many
treatment issues, including selection of patients for treatment, duration of
antiviral therapy, the role of combination therapy with two antivirals or an
antiviral with pegylated interferon, remain unresolved and need to be
elucidated through further clinical studies. Many clinicians are currently
treating patients indefinitely with antivirals in order to maintain viral
suppression (Hoofnagle, 2006).
Study objective
The primary objective of this study is to demonstrate the superior antiviral
efficacy of the combination of peginterferon alpha-2a plus telbivudine vs
peginterferon alpha-2a monotherapy as demonstrated by HBV DNA non-detectability
using the COBAS Amplicor HBV Monitor* assay (threshold for detection 300
copies/mL) at Week 52 in adult patients with HBeAg-positive CHB.
The key secondary objectives of the study are
* Demonstrate that telbivudine monotherapy has superior antiviral efficacy
compared to peginterferon alpha-2a monotherapy as shown via PCR
non-detectability at Week 52.
* Compare the antiviral efficacy of the combination of peginterferon alpha-2a
plus telbivudine to telbivudine monotherapy at Week 52
Other secondary objectives evaluated at various time points include:
* Assessment HBV DNA non-detectability, reduction from baseline and sustained
reduction in HBV DNA over the course of the study.
* Assessment Virologic Breakthrough (See glossary of terms) and treatment
emergent HBV resistance at Weeks 48 and 96
* Assessment of HBeAg loss and HBeAg seroconversion (defined as loss of HBeAg
and development of HBeAb).
* Assessment of HBsAg loss
* Assessment of ALT normalization
Study design
This is a randomized, open-label, global, multicenter, three-arm, study
comparing peginterferon alpha-2a plus telbivudine combination therapy to
peginterferon alpha-2a monotherapy and telbivudine monotherapy in adult
HBeAg-positive outpatients with CHB.
As there are a number of approved therapies a placebo treatment arm will not be
included in this study as it would be unethical.
Intervention
There are three treatment groups:
1)Telbivudine monotherapy: 104 weeks of oral therapy
2)Combination therapy: 52 weeks of peginterferon alpha-2a and 104 weeks of
telbivudine
3)Peginterferon alpha-2a monotherapy: 52 weeks of peginterferon alpha-2a
Peginterferon alpha-2a will be used in the first 52 weeks of the study as
monotherapy and in combination therapy.
Study burden and risks
Risks are possible side effects of study medicine or another medicine, and
those of taking blood. The most common side effects reported to date with
telbivudine are:
flu, headache, tiredness, stomach pain, sore throat, cough, diarrhea, dizziness
and creatine kinase enzym elevations.
The most common side effects reported to date with peginterferon alpha 2a:
fever, headache, initial drop of hemoglobine, tiredness, muscle aches, hair
loss and decrease in appetite. Very rare side effects are mood and behavorial
problems, decrease in white blood cells, and serious infections.
Problems or side effects that are not known could also occur.
20 visits have to be payed to the medical center. The tests done at each visit
are standard medical tests. More blood samples than standard medical care will
be taken at every visit.
The blood pressure cuff may also cause discomfort or bruising to the upper arm.
Bloodpressure will be taken every visit, physical examinations, ECG, are
routine procedures in clinical practice and present practically no risk to the
patient.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
1. Male or female, at least 18 years of age.
2. Documented Cronic Hepatitis B (CHB) defined by all of the following:
*Clinical history compatible with CHB
*Detectable serum HBsAg at the Screening visit and at least 6 months prior
*HBeAg-positive at the Screening visit
*HBeAb-negative at the Screening visit
*Documented history of evidence of chronic liver inflammation,
*Elevated serum ALT level (1.3 * 10 x upper limit of normal (ULN)) at screening
*Serum HBV DNA level * 6 log10 copies/mL (central lab), at screening
*Documented chronic liver inflammation on previous liver biopsy within the previous 24 months
Exclusion criteria
1. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures or their excipients.
2. Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), or Human immunodeficiency virus (HIV).
3. Current or passed use of excluded drug therapy e.g. other investigational therapy, immunomodulatory treatment, nucleoside or nucleoitide therapy
4. Medical condition requiring prolonged use of corticosteroids, hepatotoxic drugs or nephrotoxic drugs.
5. Alcohol or illicit drug abuse within the preceding 2 years
6. Patient is on thyroid therapy and dose is not stable for at least 5 weeks prior to Visit 2/Baseline
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR200-004003-18-NL |
| CCMO | NL14500.091.06 |