Ignite Creation Date:
2025-12-24 @ 9:42 PM
Ignite Modification Date:
2026-02-22 @ 3:56 PM
Study NCT ID:
NCT03681132
Status:
COMPLETED
Last Update Posted:
2023-03-20
First Post:
2018-09-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Norwegian Nucleoside Analogue Stop Study
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'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 127}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-09-20', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-03', 'completionDateStruct': {'date': '2023-01-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-03-17', 'studyFirstSubmitDate': '2018-09-20', 'studyFirstSubmitQcDate': '2018-09-20', 'lastUpdatePostDateStruct': {'date': '2023-03-20', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-09-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-01-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'HBsAg loss', 'timeFrame': 'Within 3 years after stopping therapy', 'description': 'Undetectable HBsAg measured by a standard assay'}], 'secondaryOutcomes': [{'measure': 'Time to HBsAg loss', 'timeFrame': 'Within 3 years after stopping therapy', 'description': 'Time from randomization to undetectable HBsAg'}, {'measure': 'Time to re-start of antiviral therapy', 'timeFrame': 'Within 3 years after stopping therapy', 'description': 'Time from randomization to re-start of therapy according to the specified criteria'}, {'measure': 'Severe unintended medical events', 'timeFrame': 'Within 3 years after stopping therapy', 'description': 'Liver failure or other liver-related grade 4/5 SAEs'}, {'measure': 'Immune control', 'timeFrame': 'Within 3 years after stopping therapy', 'description': 'Sustained off-therapy response viz HBV DNA \\<2000 IU/ml and ALT \\<40 U/L'}, {'measure': 'Changes in health-related quality of life', 'timeFrame': 'Within 3 years after stopping therapy', 'description': 'Changes in the EuroQol standardized measure of health status (EQ-5D-5L) score. The summary index (from 0 to 1) as described by the manufacturer (euroqol.org) will be employed.'}, {'measure': 'Liver fibrosis evolution', 'timeFrame': 'Within 3 years after stopping therapy', 'description': 'Changes in transient elastography from baseline'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Hepatitis B, Chronic']}, 'referencesModule': {'references': [{'pmid': '38114718', 'type': 'DERIVED', 'citation': 'Holmberg M, Aass HCD, Dalgard O, Samuelsen E, Sun D, Bjorkstrom NK, Johannessen A, Reikvam DH. Treatment cessation in HBeAg-negative chronic hepatitis B: clinical response is associated with increase in specific proinflammatory cytokines. Sci Rep. 2023 Dec 18;13(1):22590. doi: 10.1038/s41598-023-50216-y.'}]}, 'descriptionModule': {'briefSummary': 'Globally, an estimated 257 million individuals have chronic hepatitis B-virus infection (CHB). In the absence of treatment 15-40% of these will progress to liver cirrhosis and/or hepatocellular carcinoma. Oral antiviral treatment suppresses the virus and improves prognosis, but less than 0.5% per year achieve a "functional cure" (i.e. HBsAg loss). One remaining controversy, therefore, is whether antiviral treatment must continue life-long. Observational studies have assessed stopping antiviral treatment after years of viral suppression; however, HBsAg loss has rarely been seen. But interestingly, a few small trials that chose watchful waiting instead of re-initiation of treatment when reactivation occurred, achieved 40% HBsAg loss during 6 years follow-up.\n\nThe present proposal is a randomized controlled trial that will assess the safety, efficacy, and cost-effectiveness of treatment discontinuation - and delayed restart - in HBeAg negative CHB. The study is sufficiently powered to address the hypotheses, and a pilot study that demonstrates feasibility has been performed. Patients will be enrolled at 12 Norwegian hospitals, in addition to our collaborating institution in Ethiopia - the largest CHB treatment center in sub-Saharan Africa. If the study shows that discontinuation is safe and effective, it will directly impact both national and international treatment guidelines.\n\nMain objective:\n\n-To study whether stopping nucleoside analogue (NA) therapy - and delaying re-start - can trigger an immune response and set off a functional cure (viz HBsAg loss)\n\nSecondary objectives:\n\n* Assess whether stopping NA therapy - and delaying re-start - leads to a higher chance of HBsAg loss\n* Assess the safety of stopping NA therapy - and delaying re-start - in terms of hepatic decompensation, fibrosis progression, and/or adverse events\n* Study whether stopping NA therapy - and delaying re-start - leads to a higher chance of sustained off-therapy immune control (low viral load and normal ALT)\n* Assess the quality of life and cost-effectiveness of stopping NA therapy - and delaying re-start\n* Identify predictors of HBsAg loss'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Adults (18-70 years) with HBeAg negative chronic hepatitis B\n* HBeAg negative at start of antiviral therapy\n* Treated minimum 2 years with either tenofovir or entecavir without interruption (i.e. no self-reported episodes of ≥2 weeks off therapy)\n* Full viral suppression \\>2 years: at least 3 measurements at least 6 months apart with at least 24 months between the first and last measurement.\n* Most recent liver fibrosis assessment, performed within the past 12 months, does not show advanced fibrosis (i.e. Metavir score \\<F3 or Fibroscan \\<9 kPa). For the (few) patients who lack pre-treatment fibrosis assessment, a more conservative Fibroscan threshold of \\<8 kPa will apply.\n\nExclusion Criteria:\n\n* A history of decompensated liver disease, either by clinical signs (ascites, encephalopathy, portal hypertension, jaundice) or suggestive laboratory results (total bilirubin \\>38 umol/L, INR \\>1.5, platelets \\<75,000/mm3, serum albumin \\<30 g/L).\n* Any previous diagnosis of cirrhosis, either by liver biopsy (Metavir score F4) or elastography (Fibroscan \\>12 kPa). Elastography results with concomitant ALT \\>200 U/L are not considered.\n* Previous hepatocellular carcinoma (HCC).\n* Co-infections with HIV, hepatitis C or hepatitis D.\n* Other disease or medication that can interfere with the study (e.g. ongoing alcohol or illicit drug abuse, immunosuppressive medication, other active liver disease, or any other condition which in the opinion of the physician is incompatible with participation)'}, 'identificationModule': {'nctId': 'NCT03681132', 'acronym': 'Nuc-Stop', 'briefTitle': 'The Norwegian Nucleoside Analogue Stop Study', 'organization': {'class': 'OTHER', 'fullName': 'Oslo University Hospital'}, 'officialTitle': 'The Norwegian Nucleoside Analogue Stop Study: a Randomized Open-label Trial in HBeAg Negative Chronic Hepatitis B, Aiming at Achieving a Functional Cure.', 'orgStudyIdInfo': {'id': '2018/988'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'Low-threshold re-start', 'description': 'Re-start antiviral therapy if HBV DNA viral load \\>2000 IU/ml and ALT \\>80 U/L.', 'interventionNames': ['Other: Stop of therapy']}, {'type': 'OTHER', 'label': 'High-threshold re-start', 'description': 'Re-start antiviral therapy if:\n\n* ALT \\>100 U/L persisting for more than 4 months without any spontaneous decline toward normal; OR\n* ALT \\>400 U/L persisting for more than 2 months in consecutive assays.', 'interventionNames': ['Other: Stop of therapy']}], 'interventions': [{'name': 'Stop of therapy', 'type': 'OTHER', 'description': 'The active intervention is to stop antiviral therapy, and delay re-start in the high-threshold group.', 'armGroupLabels': ['High-threshold re-start', 'Low-threshold re-start']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Copenhagen', 'country': 'Denmark', 'facility': 'Hvidovre Hospital', 'geoPoint': {'lat': 55.67594, 'lon': 12.56553}}, {'city': 'Addis Ababa', 'country': 'Ethiopia', 'facility': 'St Paul Hospital Millennium Medical College', 'geoPoint': {'lat': 9.02497, 'lon': 38.74689}}, {'city': 'Ålesund', 'country': 'Norway', 'facility': 'Ålesund Hospital', 'geoPoint': {'lat': 62.47225, 'lon': 6.15492}}, {'city': 'Bodø', 'country': 'Norway', 'facility': 'Bodø Hospital', 'geoPoint': {'lat': 67.28267, 'lon': 14.37513}}, {'city': 'Drammen', 'country': 'Norway', 'facility': 'Drammen Hospital', 'geoPoint': {'lat': 59.74389, 'lon': 10.20449}}, {'city': 'Lørenskog', 'country': 'Norway', 'facility': 'Akershus University Hospital'}, {'city': 'Oslo', 'country': 'Norway', 'facility': 'Oslo University Hospital', 'geoPoint': {'lat': 59.91273, 'lon': 10.74609}}, {'city': 'Sandvika', 'country': 'Norway', 'facility': 'Bærum Hospital', 'geoPoint': {'lat': 64.46377, 'lon': 13.59125}}, {'city': 'Stavanger', 'country': 'Norway', 'facility': 'Stavanger University Hospital', 'geoPoint': {'lat': 58.97005, 'lon': 5.73332}}, {'city': 'Tønsberg', 'country': 'Norway', 'facility': 'Tønsberg Hospital', 'geoPoint': {'lat': 59.26754, 'lon': 10.40762}}, {'city': 'Stockholm', 'country': 'Sweden', 'facility': 'Karonlinska University Hospital', 'geoPoint': {'lat': 59.32938, 'lon': 18.06871}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Oslo University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'University Hospital, Akershus', 'class': 'OTHER'}, {'name': 'Addis Ababa University', 'class': 'OTHER'}, {'name': "St. Paul's Hospital Millennium Medical College, Ethiopia", 'class': 'OTHER'}, {'name': 'South-Eastern Norway Regional Health Authority, Norway', 'class': 'UNKNOWN'}, {'name': 'Bærum Hospital, Norway', 'class': 'UNKNOWN'}, {'name': 'Drammen Hospital, Norway', 'class': 'UNKNOWN'}, {'name': 'Tønsberg Hospital, Norway', 'class': 'UNKNOWN'}, {'name': 'Helse Stavanger HF', 'class': 'OTHER_GOV'}, {'name': 'Ålesund Hospital, Norway', 'class': 'UNKNOWN'}, {'name': 'Bodø Hospital, Norway', 'class': 'UNKNOWN'}, {'name': 'Hvidovre University Hospital', 'class': 'OTHER'}, {'name': 'Karolinska University Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Consultant/ researcher', 'investigatorFullName': 'Asgeir Johannessen', 'investigatorAffiliation': 'Oslo University Hospital'}}}}