| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | To assess antiviral efficacy (serum HBV DNA reductions) in hepatitis B patients
randomly switched to telbivudine or continued on lamivudine treatment after 3-12 months of previous treatment with lamivudine. | |
| E.2.2 | Secondary objectives of the trial | To compare clinical efficacy outcomes. Clinical efficacy will be assessed by serum ALT normalization and a composite serologic efficacy endpoint termed Therapeutic Response (HBV DNA < 5 log10 copies/mL with HBeAg loss or ALT normalized). The number of patients with HBV DNA PCR negative and HBeAg responses (HBeAg loss and seroconversion) will be assessed in an exploratory fashion, in the patient subgroup who are HBeAg-seropositive at study entry.
To compare clinical and laboratory safety observations.
To characterize the frequency of viral breakthrough, and treatment-emergent HBV viral genotypes associated with viral breakthrough.
The featured data analyses will be targeted to 12, 24, and 52 weeks after initiation of study treatment. The final data analysis is the Week 52 analysis.
| |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Patients must meet all of the following inclusion criteria:
Male or female, 18 to 70 years of age
Documented compensated chronic hepatitis B defined by all of the following:
• Clinical history compatible with compensated chronic hepatitis B
• Detectable serum HBsAg at the Screening visit
• HBeAg seropositive or seronegative
• History of evidence of chronic liver inflammation, documented by previous history
of elevated serum ALT and/or AST levels (at least two elevated ALT or AST values
spanning six months or more, documented in available records), and/or chronic
liver inflammation documented on previous liver biopsy with available pathology
report.
• Serum ALT level at Screen < 10 x ULN
• Serum HBV DNA > 3 log10 copies/mL by the COBAS Amplicor HBV PCR assay at
the central study laboratory
Patient is currently receiving lamivudine treatment for his/her hepatitis B, and has
received lamivudine continuously for a duration of at least 12 weeks (3 months) and
not more than one year (12 months). The start of lamivudine therapy must be
documented in the patient’s available medical records.
Patient is willing and able to comply with the study drug regimen and all other study
requirements.
The patient is willing and able to provide written informed consent to participate in the study. | |
| E.4 | Principal exclusion criteria | Patient is pregnant or breastfeeding.
Patient is of childbearing potential (men and women) and unwilling to use a barrier
method of contraception. It is required that a barrier method of contraception be
used (i.e. condom with spermicide or diaphragm with spermicide) by patients of
childbearing potential (men and women) regardless of whether a hormonal agent
also is used as a method of contraception.
Patient is coinfected with hepatitis C virus (HCV), hepatitis D virus (HDV), HIV-1 or
HIV-2. Patients will be tested for antibodies to HCV, HIV, and HDV in the
Screening assessments performed at the central laboratory.
Patient previously received antiviral treatment for hepatitis B other than lamivudine
in the preceding 12 months. Precluded therapies include, but are not limited to,
the following: interferon alpha-, beta-, or gamma-interferon), adefovir dipivoxil or
other PMEA analogs (tenofovir, MCC-478), ganciclovir, ribavirin, entecavir, emtricitabine (FTC), L-FMAU, L-Fd4C, or other investigational anti-HBV
nucleosides/nucleotides.
Patient has received other systemic immunomodulatory treatment for HBV infection in the preceding 12 months. Precluded therapies include, but are not limited to any exposure to thymosin, IL-12, or other putative systemic immunomodulators.
Patient has a medical condition that requires prolonged or frequent use of systemic
acyclovir or famciclovir. Prolonged use means episodic treatment with these agents for periods exceeding 10 days every 3 months, or chronic suppressive therapy.
A history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of hepatic decompensation.
Patient has a history of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha-fetoprotein (AFP) levels. In patients with such findings, HCC should be ruled-out prior to randomization for the present study.
Patient is currently abusing alcohol or illicit drugs, or has a history of alcohol abuse
or illicit substance abuse within the preceding two years. For the purposes of the
present study, alcohol abuse is defined as frequent consumption of alcoholic beverages with an average daily intake of more than 40 g of ethanol. Patients
currently on methadone maintenance treatment programs are NOT eligible for this
study due to potential interference with study evaluations.
Patient has a medical condition that requires frequent or prolonged use of systemic
corticosteroids
Patient has one or more additional known primary or secondary causes of liver
disease, other than hepatitis B. Gilbert’s syndrome and Dubin-Johnson syndrome, two benign disorders associated with low-grade hyberbilirubinemia, will not exclude patients from participation in this trial. The presence of either of these two disorders should be so indicated on the appropriate page in the case report form.
Patient has any other concurrent medical condition likely to preclude compliance
with the schedule of evaluations in the protocol, or likely to confound the efficacy or
safety observations of the study (e.g., concurrent malignancies, history of unstable
angina, repeated myocardial infarction or congestive heart failure, renal insufficiency, uncontrolled asthma or diabetes, unstable thyroid disease or other significant hormonal conditions, uncontrolled seizure disorders, severe psychiatric disorders, active tuberculosis under current treatment, etc.). A history of treated malignancy (other than hepatocellular carcinoma) is allowable if the patient’s malignancy has been in complete remission off chemotherapy and without additional surgical interventions during the preceding three years.
Patient has a history of clinical pancreatitis.
Patient is enrolled or plans to enroll in another clinical trial of an investigational
agent while participating in this study.
Patient has any of the following laboratory values at Screening:
• Hemoglobin <11 g/dL for men or < 10 g/dL for women [Female <100 g/L;
Male <110 g/L
• Total WBC < 3,000/ mm3
• Absolute neutrophil count (ANC) < 1,500/mm3 [<1.50 x 109/L]
• Platelet count < 75,000/mm3 [<75 x 109/L]
• Serum albumin < 3.3 g/dL [<33g/L]
• Total bilirubin ≥ 2.0 mg/dl [ > 34 µmol/L]
• Serum creatinine > 1.5 mg/dl [Female >106 µmol/L; Male >115 µmol/L]
• AFP > 50 ng/mL [>50 µg/L] (requires further evaluation, to rule-out hepatocellular carcinoma)
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | The primary endpoint will be reduction from study Baseline in serum HBV DNA level,
involving a comparison of results with telbivudine treatment (Group A) vs. continued
lamivudine treatment (Group B).
Featured data analyses on the primary endpoint and the secondary endpoints will
occur at Weeks 12, 24, and 52. The main purpose of this interim analysis is to assure
that continued pursuit of the scientific goals of the study is reasonable, by assessing
whether the switch from lamivudine to telbivudine is, at least, not likely to produce any efficacy detriment for the patients. The principal treatment comparison on the primary endpoint will be the Week 24 comparison, with the Week 52 analysis considered to be confirmatory. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.3.1 | Comparator description | |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
