Ignite Creation Date:
2025-12-25 @ 2:54 AM
Ignite Modification Date:
2025-12-26 @ 1:35 AM
Study NCT ID:
NCT00117533
Status:
UNKNOWN
Last Update Posted:
2006-05-25
First Post:
2005-06-30
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Pegylated Interferon Alfa-2b Plus Ribavirin in Chronic Hepatitis B and Delta
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019694', 'term': 'Hepatitis B, Chronic'}, {'id': 'D019701', 'term': 'Hepatitis D, 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'}, {'id': 'D003699', 'term': 'Hepatitis D'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D012254', 'term': 'Ribavirin'}], 'ancestors': [{'id': 'D012263', 'term': 'Ribonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'count': 20}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2005-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2005-09', 'completionDateStruct': {'date': '2007-06'}, 'lastUpdateSubmitDate': '2006-05-24', 'studyFirstSubmitDate': '2005-06-30', 'studyFirstSubmitQcDate': '2005-06-30', 'lastUpdatePostDateStruct': {'date': '2006-05-25', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2005-07-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'the efficacy of 24-week pegylated IFN alfa-2b plus RBV for SVR of HDV in patients with dual chronic hepatitis D and B'}], 'secondaryOutcomes': [{'measure': 'the efficacy of pegylated IFN alfa-2b plus RBV in patients with dual chronic hepatitis D and B on: The biochemical response rate'}, {'measure': 'The degree of histologic change'}]}, 'conditionsModule': {'keywords': ['chronic hepatitis B;', 'chronic hepatitis delta;', 'treatment;', 'pegylated interferon alfa-2b;', 'ribavirin'], 'conditions': ['Chronic Hepatitis B', 'Chronic Hepatitis D']}, 'descriptionModule': {'briefSummary': 'The treatment of choice for chronic hepatitis D is uncertain. The investigators hypothesize that pegylated interferon (IFN) alfa-2b in combination with ribavirin (RBV) may be effective in the treatment of chronic hepatitis D patients who are also infected by hepatitis B virus (HBV). The purpose of this study is to test this hypothesis. The investigators will use pegylated IFN alfa-2b in combination with RBV for the treatment of patients with dual chronic hepatitis D virus (HDV) and HBV infection. A 24-week course of combination therapy pegylated IFN+RBV will be used.', 'detailedDescription': 'Recombinant IFN alfa possesses anti-viral and immunomodulatory effects and has been shown to be effective in chronic hepatitis B \\[Davis et al. 1989; Bisceclie et al, 1989\\]. Interferon alfa is also one of the approved treatments for chronic hepatitis B. Administration of IFN alfa-2b to adults leads to disappearance of HBV DNA with or without HBeAg seroconversion in 30-50% of patients, which is two to three times above the rate of yearly spontaneous HBeAg seroconversion (10-15%). Normalization of serum ALT occurs in most cases. Loss of HBsAg is observed in 10-15% of Caucasian patients during the prolonged post-treatment follow-up period. Recently, studies suggested that a higher proportion of patients receiving pegylated IFN could achieve HBeAg seroconversion and control of HBV replication \\[Marcellin et al, 2004; Lau et al, 2004; Jensen et al, 2004\\].\n\nRBV is another antiviral nucleotide analogue with few adverse effects \\[Sidwell et al, 1972; Patterson et al, 1990\\]. RBV alone can modestly inhibit HDV or HBV replication \\[Choi et al, 1989\\]. The beneficial effect of combined IFN plus RBV in the treatment of chronic hepatitis B has also been shown in previous studies \\[Cotonat et al, 2000\\]. Why RBV can greatly enhance the treatment efficacy is not clear. It had been shown that ribavirin could inhibit interleukin-4, an inhibitor of cytotoxic T lymphocyte activity, and preserves the interleukin-2 and gamma IFN activities. Other studies revealed that the enhanced efficacy was associated with HBV- or other virus-specific type 1 cytokine-mediated T helper cell responses \\[Cramp et al, 2000; Tam et al, 1999; Hultgren et al, 1998; Fang et al, 2002; Fang et al, 2000; Rico et al, 2001\\]. Thus, the combination therapy may augment virus-specific cytotoxic T lymphocytes and non-specific immune response, and effectively shift the immune responses to the more potent antiviral type 1 T-helper profile \\[Hultgren et al, 1998\\].\n\nHDV, like HCV, is a RNA virus. Indeed, RBV had also been shown to be active against HDV replication in cell cultures \\[Choi et al, 1989\\]. The investigators therefore hypothesize that pegylated IFN alfa-2b in combination with RBV can yield an efficacy in chronic hepatitis D patients who are dually infected by HBV. The purpose of this protocol is to test this hypothesis. A previous study found that high-dose IFN may improve the efficacy for chronic hepatitis D patients. Another pilot study using IFN alfa plus RBV also demonstrated that the seroclearance of HCV RNA was not affected by HBV coinfection \\[Liu et al, 2003\\]. The investigators thus use pegylated IFN alfa-2b in combination with RBV for the treatment of patients with dual chronic HDV and HBV infection.\n\nThe treatment choice for chronic hepatitis D was not clarified till now. In this proposal, the dosage and duration for the combination regimen are decided mainly by the experience from the treatment of chronic hepatitis B and chronic hepatitis C.\n\nThe investigators recent study using ribavirin and interferon (IFN) combination therapy for dual chronic hepatitis B and C suggested that combining ribavirin 1,200 mg daily for 6 months, together with 6 million units (MU) IFN-alpha 2a thrice weekly for 12 weeks and then 3 MU for another 12 weeks was effective for the clearance of HCV RNA \\[Liu et al, 2003\\]. Twenty-four patients with chronic hepatitis seropositive for both hepatitis B surface antigen and antibody to HCV received ribavirin 1,200 mg daily for 6 months, together with 6 million units (MU) IFN-alpha 2a thrice weekly for 12 weeks and then 3 MU for another 12 weeks. The serum HCV clearance rate was 43% 24 weeks posttreatment. The serum ALT normalization rate was 43% 24 weeks posttreatment. In hepatitis B and C dually infected patients, combination IFN with ribavirin can achieve a sustained HCV clearance rate comparable with hepatitis C alone. Furthermore, a previous study revealed that a 12-week RBV therapy was not effective for patients with chronic hepatitis B \\[Kakumu et al, 1993\\]. Therefore, a 24-week course of combination therapy pegylated IFN+RBV will be used.\n\nIncreased RBV dosage has been considered a contributory factor to the better efficacy in treating refractory genotype HCV. For example, recent studies suggested that using RBV 800 mg daily is adequate to treat HCV genotype non-1 while the standard dosage of RBV is required to treat HCV genotype 1 \\[NIH 2002\\]. The investigators thus propose to use RBV 1000-1200 mg daily according to the body weight of the patient.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Be positive for both anti-HDV and HBsAg for more than 6 months\n* Present with elevated serum ALT levels at least 1.5 times the upper limit of normal, documented on two occasions (at least one month apart), within six months prior to enrollment\n* Be HDV RNA positive by PCR (sensitivity: 103 copies/mL) \\[Yamashiro et al, 2004\\]\n* Be HBV DNA positive by PCR\n* Present with liver biopsy findings compatible with the diagnosis of chronic liver disease (the liver biopsy needs to be taken within 52 weeks prior to enrollment)\n* Have adequate liver reserve (defined as equal to or better than Child-Pugh Class A)\n* Present with WBC ≥3000/mm3, ANC ≥1500/mm3, and platelet ≥80,000/mm3\n* Be able to and likely to attend regularly for treatment and follow-up\n* Give their written informed consent\n* Be negative for urine pregnancy test (for females of childbearing potential), documented once within the screening period and again within 24 hours prior to the first dose of study drug\n* All male patients with female partners of childbearing age should use a barrier method of contraception\n* All female patients of childbearing potential must use two reliable forms of effective contraception\n\nExclusion Criteria:\n\n* Drug addicts or have any history or histological evidence of alcohol abuse, or currently receive prescriptions that may cause hepatotoxicity\n* Have decompensated cirrhosis as coded by Child-Pugh classification (i.e. history of ascites, history of bleeding from esophageal varices, severe portal hypertension, serum albumin \\<30 g/l, serum bilirubin \\>30 mg/l)\n* Present with WBC \\<3000/mm3, ANC \\<1500/mm3, or platelets \\<90,000/mm3\n* Present with hemoglobin \\<12.0 gm/dl for female and \\<13.0 gm/dl for male\n* Have been treated with immunosuppressive therapy within the past six months (e.g. steroids, azathioprine, cyclophosphamide)\n* Have renal insufficiency (serum creatinine \\>150 μmol/l)\n* Have clotting abnormalities which preclude a liver biopsy\n* Have evidence of any serious neurological dysfunction\n* Have obesity or diabetes mellitus-induced liver disease\n* Have serological evidence of autoimmune chronic liver disease (e.g. antinuclear antibody titers \\>1:320, and/or smooth muscle antibody titers\\>1:160)\n* Hemophiliacs\n* Have evidence of inheritable disorders such as haemochromatosis, alpha-1-antitrypsin deficiency or Wilson's disease\n* Have been exposed to hepatotoxic substances which might be the cause of hepatitis\n* Pregnant, lactating or not practicing an adequate form of birth control, such as oral contraceptives or intrauterine devices\n* Seropositive for anti-HIV or anti-HCV\n* Have serious psychological or psychiatric problems disrupting daily activities\n* Have AFP (alpha-fetoprotein) greater than 20 ng/ml; in case of elevated AFP, abdomen ultrasonography is required to exclude the possibility of HCC\n* Have serious heart diseases (coronary heart disease, etc)\n* Have a history of asthma or drug allergy which may lead to hypersensitivity to ribavirin"}, 'identificationModule': {'nctId': 'NCT00117533', 'briefTitle': 'Pegylated Interferon Alfa-2b Plus Ribavirin in Chronic Hepatitis B and Delta', 'organization': {'class': 'OTHER', 'fullName': 'National Taiwan University Hospital'}, 'officialTitle': 'A Pilot Study to Evaluate the Efficacy and Safety of Pegylated Interferon Alfa-2b Plus Ribavirin in the Treatment of Patients With Dual Chronic Hepatitis B and Delta', 'orgStudyIdInfo': {'id': '930904'}}, 'armsInterventionsModule': {'interventions': [{'name': 'pegylated IFN alfa-2b plus ribavirin', 'type': 'DRUG'}]}, 'contactsLocationsModule': {'locations': [{'zip': '100', 'city': 'Taipei', 'state': 'Taipei', 'status': 'RECRUITING', 'country': 'Taiwan', 'facility': 'National Taiwan University Hospital'}, {'zip': '100', 'city': 'Taipei', 'state': 'Taipei', 'status': 'NOT_YET_RECRUITING', 'country': 'Taiwan', 'contacts': [{'name': 'Pei-Jer Chen, M.D.; Ph.D.', 'role': 'CONTACT', 'email': 'peijer@ha.mc.ntu.edu.tw', 'phone': '886-2-23123456', 'phoneExt': '7072'}, {'name': 'Pei-Jer Chen, M.D., Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'National Taiwan University'}], 'centralContacts': [{'name': 'Pei-Jer Chen, M.D., Ph.D.', 'role': 'CONTACT', 'email': 'peijer@ha.mc.ntu.edu.tw', 'phone': '886-2-23123456', 'phoneExt': '7072'}], 'overallOfficials': [{'name': 'Pei-Jer Chen, M.D., Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'National Taiwan University Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Taiwan University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Health Research Institutes, Taiwan', 'class': 'OTHER'}, {'name': 'National Science and Technology Council, Taiwan', 'class': 'OTHER_GOV'}]}}}