Ignite Creation Date:
2025-12-25 @ 2:27 AM
Ignite Modification Date:
2025-12-27 @ 11:19 PM
Study NCT ID:
NCT01597934
Status:
UNKNOWN
Last Update Posted:
2014-01-31
First Post:
2012-05-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Antiviral Efficacy of Switching to ETV Plus TDF
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019694', 'term': 'Hepatitis B, Chronic'}], 'ancestors': [{'id': 'D006509', 'term': 'Hepatitis B'}, {'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D018347', 'term': 'Hepadnaviridae Infections'}, {'id': 'D004266', 'term': 'DNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D006525', 'term': 'Hepatitis, Viral, Human'}, {'id': 'D006521', 'term': 'Hepatitis, Chronic'}, {'id': 'D006505', 'term': 'Hepatitis'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D019259', 'term': 'Lamivudine'}, {'id': 'D000077712', 'term': 'Telbivudine'}, {'id': 'C106812', 'term': 'adefovir dipivoxil'}, {'id': 'C413685', 'term': 'entecavir'}, {'id': 'D000068698', 'term': 'Tenofovir'}], 'ancestors': [{'id': 'D016047', 'term': 'Zalcitabine'}, {'id': 'D003841', 'term': 'Deoxycytidine'}, {'id': 'D003562', 'term': 'Cytidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D003853', 'term': 'Deoxyribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D015224', 'term': 'Dideoxynucleosides'}, {'id': 'D013936', 'term': 'Thymidine'}, {'id': 'D063065', 'term': 'Organophosphonates'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000225', 'term': 'Adenine'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 104}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2012-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-01', 'completionDateStruct': {'date': '2014-05', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2014-01-30', 'studyFirstSubmitDate': '2012-05-08', 'studyFirstSubmitQcDate': '2012-05-14', 'lastUpdatePostDateStruct': {'date': '2014-01-31', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2012-05-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-05', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time PCR at Week 48', 'timeFrame': 'at Week 48', 'description': 'To compare the proportion of subjects who achieve virologic response(HBV DNA \\< 60 IU/mL, approximately 300 copies/mL) in switching group(Entecavir plus Tenofovir) with that in maintaining group(Lamivudine/Telbivudine plus Adefovir) by real-time Polymerase chain reaction(PCR) at Week 48'}], 'secondaryOutcomes': [{'measure': 'Virologic efficacy', 'timeFrame': 'Week 12, 24, 36, and 48', 'description': 'To compare virologic response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48'}, {'measure': 'serologic efficacy', 'timeFrame': 'Week 12, 24, 36, and 48', 'description': 'To compare serologic response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48'}, {'measure': 'biochemical efficacy', 'timeFrame': 'Week 12, 24, 36, and 48', 'description': 'To compare biochemical response in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48'}, {'measure': 'Safety issue', 'timeFrame': 'Week 12, 24, 36, and 48', 'description': 'To compare safety issue in switching group(Entecavir plus Tenofovir) with those in maintaining group (Lamivudine/Telbivudine plus Adefovir) at Week 48 - severity of adverse event'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Chronic hepatitis B', 'Partial virologic response', 'YMDD mutation'], 'conditions': ['Chronic Hepatitis B']}, 'referencesModule': {'references': [{'pmid': '32460460', 'type': 'DERIVED', 'citation': 'Woo HY, Park JY, Bae SH, Kim CW, Jang JY, Tak WY, Kim DJ, Kim IH, Heo J, Ahn SH. Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response. Clin Mol Hepatol. 2020 Jul;26(3):352-363. doi: 10.3350/cmh.2019.0044n. Epub 2020 May 28.'}]}, 'descriptionModule': {'briefSummary': 'Switching to Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will result in faster and greater antiviral activity and lower rates of resistance emergence over maintaining Lamivudine(LAM)/Telbivudine(LdT)+Adefovir(ADV) combination in partial responders to LAM/LdT+ADV rescue therapy.\n\nEarlier switching to combination with the most potent regimen will be more effective to achieve virologic response(VR) and prevent further resistance emergence.\n\nAll subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.', 'detailedDescription': "1. As TDF has not been approved yet in Korea, current KASL practice guideline generally recommends to add ADV in LAM-resistant or LdT-resistant patients.\n2. However, several local literatures reported a substantial proportion of patients treated with LAM plus ADV combination therapy showed a persistently inadequate or partial virologic response('VR') and YMDDm still maintained in spite of under rescue combination therapy.\n3. Due to the unavailability of TDF in Korea, ETV plus ADV combination has being considered a better salvage therapy with non-overlapping cross-resistance profiles in pts who fail to LAM plus ADV rescue therapy and local report demonstrated that the rate of VR was significantly higher with ETV+ADV switching group than LAM+ADV continuation group in partial responder to LAM plus ADV combination rescue therapy for LAM resistance.\n4. Hence, more earlier combination therapy with the most potent Nucleoside and Nucleotide analogue would be a promising salvage treatment for previous NA treatment failures but comparative prospective trials are limited.\n5. Therefore, this study will investigate the greater effectiveness and safety of switching to the most potent combination versus maintaining LAM(or LdT) plus ADV and also compare the rate of VR based on the HBV DNA cut-off level at switching - more than and less than 20,000 IU/mL.\n\nAll subjects will orally take assigned drugs once daily for 48 weeks. All subjects will be assessed at baseline and every three months thereafter. Evaluations at each visit will include vital signs, physical examinations, laboratory tests, HBV DNA levels and adverse events. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '20 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. ≥ 20 years of age\n2. History of HBsAg positive for more than 6 months\n3. History of genotypic resistance to LAM or LdT (YMDDm)\n4. Partial responder (HBV DNA ≥ 60 IU/mL) currently receiving antiviral combination rescue therapy for at least 24 weeks of treatment with LAM+ADV or LdT+ADV\n5. Hepatitis B e Antigen(HBeAg)-positive and -negative\n6. Compensated liver disease (Child-Pugh A)\n7. Signed written informed consent after being instructed about the objective and procedure of the clinical study\n\nExclusion Criteria:\n\n1. History of genotypic resistance to ADV\n2. Most previous treatment of other than LAM+ADV and LdT+ADV\n3. Subjects with Alanine Aminotransferase(ALT) \\> 10xUpper Limit of normal(ULN)\n4. Co-infected with hepatitis C virus(HCV) or HIV\n5. Pregnant or lactating woman\n6. Subject who needs long-term administration of drugs including immunosuppressive agents, agents related to high risk in the hepatic/renal toxicity, agents influencing renal excretion\n7. History of liver transplantation or planned for liver transplantation\n8. Subject who was diagnosed malignant tumor and has been receiving chemotherapy\n9. Subject who has HCC history or who shows potential hepatocellular carcinoma (HCC) finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation\n10. Renal Insufficiency (CLcr \\< 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)\n11. Subject who has a liver disease other than chronic hepatitis B (e.g. hemochromatosis, Wilson's disease, alcoholic liver disease, nonalcoholic fatty liver disease, alpha 1-antitrypsin deficiency etc.)\n12. Subject who has a history of hypersensitivity to study drug or its ingredients\n13. Subject who is involved in other clinical trial within 60 days prior to study entry\n14. Subject who the investigator deems inappropriate to participate in this study"}, 'identificationModule': {'nctId': 'NCT01597934', 'briefTitle': 'Antiviral Efficacy of Switching to ETV Plus TDF', 'organization': {'class': 'OTHER', 'fullName': 'Yonsei University'}, 'officialTitle': 'A Randomized, Multicenter, Prospective Study to Compare Antiviral Efficacy and Safety of Switching to ETV Plus TDF Versus Maintaining LAM/LDT Plus ADF Combination in CHC With PVR to LAM/LDF Plus ADF Combination Rescue Therapy for YMDD Mutation', 'orgStudyIdInfo': {'id': 'AI463-274'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Group A:', 'description': 'Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg', 'interventionNames': ['Drug: Group A (Zeffix, Sebivo, Hepsera)']}, {'type': 'EXPERIMENTAL', 'label': 'Group B', 'description': 'Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg', 'interventionNames': ['Drug: Group B (Baraclude, Viread)']}], 'interventions': [{'name': 'Group A (Zeffix, Sebivo, Hepsera)', 'type': 'DRUG', 'otherNames': ['Zeffix', 'Sebivo', 'Hepsera'], 'description': 'Maintaining LAM/LdT+ADV combination Lamivudine 100mg / Telbivudine 600mg +Adefovir 10mg', 'armGroupLabels': ['Group A:']}, {'name': 'Group B (Baraclude, Viread)', 'type': 'DRUG', 'otherNames': ['Baraclude', 'Viread'], 'description': 'Switching to ETV plus TDF combination Entecavir 1.0mg + Tenofovir 300mg', 'armGroupLabels': ['Group B']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Sang Hoon Ahn, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Yonsei University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Yonsei University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Bristol-Myers Squibb', 'class': 'INDUSTRY'}, {'name': "Seoul St. Mary's Hospital", 'class': 'OTHER'}, {'name': 'The Catholic University of Korea', 'class': 'OTHER'}, {'name': 'Soonchunhyang University Hospital', 'class': 'OTHER'}, {'name': 'Pusan National University Hospital', 'class': 'OTHER'}, {'name': 'Kyungpook National University Hospital', 'class': 'OTHER'}, {'name': 'Hallym University Medical Center', 'class': 'OTHER'}, {'name': 'Chonbuk National University Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'Sang Hoon Ahn', 'investigatorAffiliation': 'Yonsei University'}}}}