Hepatitis BPhase 3NCT00412750
Efficacy and Safety of Telbivudine in Treatment naïve Patients With Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB)
A Phase 3 study testing Telbivudine (LdT) and peginterferon alpha-2a in people with Hepatitis B, run by Novartis at 1 site in United States.
Trial summary
To evaluate the combination of telbivudine 600 mg orally (PO) once daily and peginterferon alpha-2a 180 ug subcutaneous (sq) injection weekly for antiviral efficacy in comparison to peginterferon alpha-2a monotherapy. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B
- What is being tested?
- Telbivudine (LdT) and peginterferon alpha-2a
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 159 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Feb 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented Chronic hepatitis B (CHB) defined by all of the following:
- Clinical history compatible with CHB
- Detectable serum Hepatitis B Surface Antigen (HBsAg) at the Screening visit and at least 6 months prior
- HBeAg-positive at the Screening visit
- Hepatitis B 'e' Antibody (HBeAb)-negative at the Screening visit
- History of evidence of chronic liver inflammation,
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- Elevated serum Alanine aminotransferase (ALT) level (1.3 - 10 x upper limit of normal (ULN)) at the Screening visit
- Serum HBV DNA level ≥ 6 log10 copies/mL,
- Chronic liver inflammation on previous liver biopsy within the previous 24 months.
Who cannot join
- Co-infection with Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), or Human Immunodeficiency Virus (HIV).
- Has any of the following drug therapy:
- Previously been treated in a trial with telbivudine
- Received nucleoside or nucleotide therapy whether approved or investigational
- Received any immunomodulatory treatment in the 12 months before Screening for this study.
- Has a medical condition that required prolonged or frequent use of systemic acyclovir or famciclovir.
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- Has a medical condition that requires frequent or prolonged use of systemic corticosteroids although inhaled or intra-articular corticosteroids are allowed.
- Has a medical condition requiring the chronic or prolonged use of potentially hepatotoxic drugs or nephrotoxic drugs.
- Is currently abusing alcohol or illicit drugs or has a history of alcohol abuse illicit substance abuse within the preceding two years.
- Uses other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
- Is currently receiving methadone.
- Patient has any of the following:
- History of or clinical signs/symptoms of hepatic decompensation such as ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis.
- History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. Patients with previous findings suggestive of possible HCC should have the disease ruled out prior to entrance into the study.
- One or more additional known primary or secondary causes of liver disease other than hepatitis B, including steatohepatitis.
- History of clinical and laboratory evidence of chronic pancreatitis, or demonstrates a clinical and laboratory course consistent with current pancreatitis.
- Has laboratory values during screening visit not within normal limits.
- Is pregnant or breastfeeding.
- Is a women of child-bearing potential that is unwilling to practice birth control.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open-label, Controlled, Multi-center Two-year Study Comparing Efficacy and Safety of Telbivudine, 600 mg PO in Combination With Peginterferon Alpha-2a sq 180 µg With Peginterferon Alpha-2a Monotherapy, and With Telbivudine Monotherapy in Treatment naïve Patients With HBeAg-positive CHB.
To evaluate the combination of telbivudine 600 mg orally (PO) once daily and peginterferon alpha-2a 180 ug subcutaneous (sq) injection weekly for antiviral efficacy in comparison to peginterferon alpha-2a monotherapy.
- Conditions
- Hepatitis B
- Being tested
- Telbivudine (LdT), peginterferon alpha-2a
- Keywords
- hepatitis B, hepatitis B Virus (HBV), chronic hepatitis B, telbivudine, peginterferon
- Medical subject headings
- Hepatitis B, Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Telbivudine (LdT)Drug
Also called Sebivo
600 mg orally once daily for 104 weeks.
peginterferon alpha-2aDrug
Also called Pegasys
180 μg subcutaneous injection once a week for 52 weeks.
| Study group | Role | What they receive |
|---|---|---|
| LdT+ PEG-INF | Experimental | Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peginterferon alpha-2a (PEG-INF)180 μg subcutaneous injection once a week for 52 weeks. Receives: Drug: Telbivudine (LdT); Drug: peginterferon alpha-2a |
| LdT Monotherapy | Experimental | Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks. Receives: Drug: Telbivudine (LdT) |
| PEG-INF Monotherapy | Active comparator | Peginterferon alpha-2a (PEG- INF) monotherapy: 180 μg subcutaneous injection once a week for 52 weeks. Receives: Drug: peginterferon alpha-2a |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Peginterferon Alpha-2a Monotherapy
The original primary efficacy variable was the percentage of patients achieving HBV DNA non-detectability utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.
Measured: At week 52
Percentage of Participants With HBV DNA Non-detectability and Alanine Aminotransferase (ALT) Normalization at Week 12 and Week 24 in Participants With HBeAg-positive Chronic Hepatitis B (CHB)
The percentage of participants who achieved HBV DNA non-detectability using the COBAS Amplicor HBV Monitor assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL) and Alanine aminotransferase (ALT) normalization defined as ALT within normal limits on two successive visits for a patient with an elevated ALT (>1.0 x upper limit normal) at baseline summarized at Weeks 12 and 24.
Measured: Weeks 12 and 24
Secondary outcomes (5)
Change From Baseline in HBV DNA Concentration
The change from baseline in HBV DNA concentration at Weeks 12 and 24 was analyzed using an analysis of covariance (ANCOVA) model with baseline HBV DNA concentration (log10 copies/ml) as a covariate, treatment and country as factors.
Measured: Weeks 12 and 24
Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52
The percentage of participants with Virologic breakthrough at Week 48 and 52 by treatment. For the subgroup of patients on treatment who achieve HBV DNA >= 1 log10 copies/mL reduction from baseline on 2 consecutive visits, Virologic Breakthrough is defined as HBV DNA >= 1 log10 copies/mL from nadir on two consecutive visits.
Measured: Weeks 48 and 52
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion
HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline. HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb). The efficacy was assessed for 18 weeks, 24 weeks, 48 weeks, 52 weeks and on treatment completion (TC).
Measured: Weeks 18, 24, 48, 52 and Treatment completion (TC)
Percentage of Participants Who Achieved HBV DNA Non-detectability With Telbivudine Monotherapy Versus Peginterferon Alpha-2a Monotherapy
Antiviral efficacy was assessed by percentage of patients achieving HBV DNA non-detectability assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.
Measured: Week 52
Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Telbivudine Monotherapy
Antiviral efficacy was assessed by percentage of patients achieving HBV DNA non-detectability assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2006 (estimated)
- Study startDec 2006
- Primary completionFeb 2009
- Study completionFeb 2009
Why it stopped: Enrollment stopped for safety issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00412750
- Sponsor's protocol ID
- CLDT600A2406
- Status last verified
- Jun 2011
- First submitted
- 15 Dec 2006
- Last updated
- 13 Jul 2011
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Marcellin P, Wursthorn K, Wedemeyer H, Chuang WL, Lau G, Avila C, Peng CY, Gane E, Lim SG, Fainboim H, Foster GR, Safadi R, Rizzetto M, Manns M, Bao W, Trylesinski A, Naoumov N. Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy. J Hepatol. 2015 Jan;62(1):41-7. doi: 10.1016/j.jhep.2014.08.021. Epub 2014 Aug 23.
PubMed 25152207
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Controlled, Multi-center Two-year Study Comparing Efficacy and Safety of Telbivudine, 600 mg PO in Combination With Peginterferon Alpha-2a sq 180 µg With Peginterferon Alpha-2a Monotherapy, and With Telbivudine Monotherapy in Treatment naïve Patients With HBeAg-positive CHB.
- ClinicalTrials.gov ID
- NCT00412750
- Acronym / sponsor ID
- CLDT600A2406
- Conditions
- Hepatitis B
- Keywords
- hepatitis B, hepatitis B Virus (HBV), chronic hepatitis B, telbivudine, peginterferon
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment stopped for safety issues
- Enrolment
- 159 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Dec 2006
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 18 Dec 2006 (estimated)
- Results
- Posted 13 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the combination of telbivudine 600 mg orally (PO) once daily and peginterferon alpha-2a 180 ug subcutaneous (sq) injection weekly for antiviral efficacy in comparison to peginterferon alpha-2a monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| LdT+ PEG-INF | Experimental | Drug: Telbivudine (LdT), Drug: peginterferon alpha-2aTelbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peginterferon alpha-2a (PEG-INF)180 μg subcutaneous injection once a week for 52 weeks. |
| LdT Monotherapy | Experimental | Drug: Telbivudine (LdT)Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks. |
| PEG-INF Monotherapy | Active comparator | Drug: peginterferon alpha-2aPeginterferon alpha-2a (PEG- INF) monotherapy: 180 μg subcutaneous injection once a week for 52 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Clinical history compatible with CHB
- Detectable serum Hepatitis B Surface Antigen (HBsAg) at the Screening visit and at least 6 months prior
- HBeAg-positive at the Screening visit
- Hepatitis B 'e' Antibody (HBeAb)-negative at the Screening visit
- History of evidence of chronic liver inflammation,
Key exclusion criteria (19 listed)
- Co-infection with Hepatitis C Virus (HCV), Hepatitis D Virus (HDV), or Human Immunodeficiency Virus (HIV).
- Has any of the following drug therapy:
- Patient has any of the following:
- Has laboratory values during screening visit not within normal limits.
- Is pregnant or breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Telbivudine (LdT)Also: Sebivo600 mg orally once daily for 104 weeks. | Drug | LdT Monotherapy, LdT+ PEG-INF |
| peginterferon alpha-2aAlso: Pegasys180 μg subcutaneous injection once a week for 52 weeks. | Drug | LdT+ PEG-INF, PEG-INF Monotherapy |
Primary outcome
Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Peginterferon Alpha-2a Monotherapy
Time frame: At week 52
The original primary efficacy variable was the percentage of patients achieving HBV DNA non-detectability utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.
Percentage of Participants With HBV DNA Non-detectability and Alanine Aminotransferase (ALT) Normalization at Week 12 and Week 24 in Participants With HBeAg-positive Chronic Hepatitis B (CHB)
Time frame: Weeks 12 and 24
The percentage of participants who achieved HBV DNA non-detectability using the COBAS Amplicor HBV Monitor assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL) and Alanine aminotransferase (ALT) normalization defined as ALT within normal limits on two successive visits for a patient with an elevated ALT (>1.0 x upper limit normal) at baseline summarized at Weeks 12 and 24.
5 secondary outcomes
Change From Baseline in HBV DNA Concentration
Time frame: Weeks 12 and 24
Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52
Time frame: Weeks 48 and 52
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion
Time frame: Weeks 18, 24, 48, 52 and Treatment completion (TC)
Percentage of Participants Who Achieved HBV DNA Non-detectability With Telbivudine Monotherapy Versus Peginterferon Alpha-2a Monotherapy
Time frame: Week 52
Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Telbivudine Monotherapy
Time frame: Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25152207Marcellin P, Wursthorn K, Wedemeyer H, Chuang WL, Lau G, Avila C, Peng CY, Gane E, Lim SG, Fainboim H, Foster GR, Safadi R, Rizzetto M, Manns M, Bao W, Trylesinski A, Naoumov N. Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy. J Hepatol. 2015 Jan;62(1):41-7. doi: 10.1016/j.jhep.2014.08.021. Epub 2014 Aug 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Telbivudine (LdT) and peginterferon alpha-2a in people with Hepatitis B, run by Novartis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Achieved HBV DNA Non-detectability With Peginterferon Alpha-2a Plus Telbivudine Combination Therapy Versus Peginterferon Alpha-2a Monotherapy (time frame: At week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00412750, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2011.