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Enrollment stopped for safety issues
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| LdT Monotherapy | Experimental | Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks. |
|
| PEG-INF Monotherapy | Active Comparator | Peginterferon alpha-2a (PEG- INF) monotherapy: 180 μg subcutaneous injection once a week for 52 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Telbivudine (LdT) | Drug | 600 mg orally once daily for 104 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Weeks 12 and 24 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Weeks 12 and 24 |
| Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52 |
Not provided
Inclusion Criteria:
Documented Chronic hepatitis B (CHB) defined by all of the following:
Exclusion Criteria:
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.
Is a women of child-bearing potential that is unwilling to practice birth control.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis | San Francisco | California | 94115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25152207 | Derived | 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. |
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This is a randomized, open-label, controlled, multi-center two-year study enrolling male and female subjects starting December 2006 and ending February 2009.
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| ID | Title | Description |
|---|---|---|
| FG000 | LdT + PEG-INF | Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks. |
| FG001 | LdT Monotherapy | Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks. |
| FG002 | PEG-INF Monotherapy | Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | LdT + PEG-INF | Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks. |
| BG001 | LdT Monotherapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The analysis was planned on intention to treat (ITT) population. Due to premature study termination, the analysis was not performed. | Posted | Number | Percentage of participants | At week 52 |
|
Not provided
Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LdT + PEG-INF | Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mitochondrial myopathy | Congenital, familial and genetic disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
Not provided
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D019694 | Hepatitis B, Chronic |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
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Not provided
| ID | Term |
|---|---|
| D000077712 | Telbivudine |
| C100416 | peginterferon alfa-2a |
| ID | Term |
|---|---|
| D013936 | Thymidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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| peginterferon alpha-2a | Drug | 180 μg subcutaneous injection once a week for 52 weeks. |
|
|
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. |
| 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). | 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. | 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. | Week 52 |
| Adverse Event |
|
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| Lack of Efficacy |
|
Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks.
| BG002 | PEG-INF Monotherapy | Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | PEG-INF Monotherapy | Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks. |
|
| Secondary | 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. | Intent to Treat (ITT) population. n= the number of patients who have both baseline and post baseline observation for the respective week | Posted | Least Squares Mean | Standard Error | log 10 copies/ml | Weeks 12 and 24 |
|
|
|
| Secondary | 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. | Intent to treat (ITT) population. As most patients did not reach Week 48 and Week 52, the LOCF was used. | Posted | Number | Percentage of participants | Weeks 48 and 52 |
|
|
|
| Secondary | 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). | Intent to Treat (ITT) population. The study was terminated and some participants did not complete all visits. "n" in each of the categories represents the number of participants in each arm with non-missing efficacy endpoint observations for the respective week and on treatment completion (TC). | Posted | Number | Percentage of participants | Weeks 18, 24, 48, 52 and Treatment completion (TC) |
|
|
|
| Secondary | 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. | The analysis was planned on intent to treat (ITT) population. Due to premature study termination, the analysis was not performed. | Posted | Number | Percentage of participants | Week 52 |
|
|
| Secondary | 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. | The analysis was planned on intent to treat (ITT) population. Due to premature study termination, the analysis was not performed. | Posted | Number | percentage of participants | Week 52 |
|
|
| Primary | 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. | Intent to Treat (ITT) population. The study was terminated and some participants did not complete all visits. "n" in each of the categories represents the number of participants in each arm with non-missing efficacy endpoint observations for the respective week. | Posted | Number | Percentage of participants | Weeks 12 and 24 |
|
|
|
| 11 |
| 50 |
| 38 |
| 50 |
| EG001 | LdT Monotherapy | Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks. | 2 | 54 | 35 | 54 |
| EG002 | PEG-INF Monotherapy | Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks. | 2 | 54 | 47 | 54 |
| Chest pain | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Hepatitis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA | Systematic Assessment |
|
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Dysaesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Polyneuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Depression suicidal | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA | Systematic Assessment |
|
| Irritability | General disorders | MedDRA | Systematic Assessment |
|
| Pain | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| D004266 |
| DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006521 | Hepatitis, Chronic |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006571 |
| Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
|
|
|
| HBeAg loss Week 24 (n=17,48,42) |
|
| HBeAg seroconversion Week 24 (n=17,48,42) |
|
| HBeAg loss Week 48 (n=0,19,12) |
|
| HBeAg seroconversion Week 48 (n=0,19,12) |
|
| HBeAg loss Week 52 (n=0,10,6) |
|
| HBeAg seroconversion Week 52 (n=0,10,6) |
|
| HBeAg loss TC (n=14,24,9) |
|
| HBeAg seroconversion TC (n=14,24,9) |
|
|
| HBV DNA non-detectability Week 24 (n=17,48,42) |
|
| ALT normalization Week 24 (n=17,48,41) |
|