- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01369199
Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B (HBRN)
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
To determine the efficacy of treatment with 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon in the treatment of chronic hepatitis B in hepatitis B "e" antigen (HBeAg) positive adults who are in the immune tolerant phase.
To evaluate safety and sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults who are in the immune tolerant phase.
A single arm treatment study of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon alfa-2a in adults with HBeAg-positive chronic hepatitis B with normal or near normal alanine aminotransferase (ALT) levels and high serum levels of hepatitis B virus (HBV) DNA ("immune tolerant" HBeAg-positive chronic hepatitis B). All participants followed for 48 weeks after treatment discontinuation (week 96 for those who completed treatment).
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 3
Kontakter og lokationer
Studiesteder
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Ontario
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Toronto, Ontario, Canada, M5T 2S8
- University of Toronto
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California
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Los Angeles, California, Forenede Stater, 90095
- University of California Los Angeles
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Los Angeles, California, Forenede Stater, 90048
- Cedars Sinai Medical Center
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San Francisco, California, Forenede Stater, 94143
- University of California San Francisco
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San Francisco, California, Forenede Stater, 94115
- California Pacific Medical Center
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Hawaii
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Honolulu, Hawaii, Forenede Stater, 96813
- Queen's Medical Center
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Maryland
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Bethesda, Maryland, Forenede Stater, 20892
- NIH Clinical Center
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Forenede Stater, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan Health System
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Minnesota
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Minneapolis, Minnesota, Forenede Stater, 55446
- University of Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic
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Missouri
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Saint Louis, Missouri, Forenede Stater, 63110
- Washington University
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Saint Louis, Missouri, Forenede Stater, 63104
- Saint Louis University
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North Carolina
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Chapel Hill, North Carolina, Forenede Stater, 27599
- University of North Carolina
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Durham, North Carolina, Forenede Stater, 27710
- Duke University Medical Center
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Texas
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Dallas, Texas, Forenede Stater, 75390
- University of Texas Southwestern
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Dallas, Texas, Forenede Stater, 75246
- Baylor University Medical Center
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Virginia
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Richmond, Virginia, Forenede Stater, 23498
- Virginia Commonwealth University
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Washington
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Seattle, Washington, Forenede Stater, 98101
- Virginia Mason Medical Center
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Seattle, Washington, Forenede Stater, 98105
- University of Washington Medical Center
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Enrolled in & completed the baseline evaluation for NCT01263587 or completed the necessary components of NCT01263587 by the end of baseline visit.
- >18 years of age at the baseline visit (day 0). Patients >50 years of age at baseline will need to have a liver biopsy as standard of care with hepatic activity index (HAI) ≤3 & Ishak fibrosis score ≤1 within 96 weeks prior to baseline visit.
- Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥24 weeks prior to baseline visit OR at least one positive HBsAg & negative anti-hepatitis B core (HBc) immunoglobulin (IgM) within 24 weeks prior to baseline visit OR at least one positive HBsAg & two positive HBV DNA over a period of ≥24 weeks prior to baseline visit.
- Presence of HBeAg in serum at last screening visit within 6 weeks of baseline visit.
- Serum HBV DNA level >10˄7 IU/mL on at least two occasions at least 12 weeks apart during the 52 weeks before baseline visit. One of the two HBV DNA levels must be within 6 weeks of baseline visit.
- ALT levels persistently ≤45 U/L in males, ≤30 U/L in females (approx. 1.5 times the upper limit of normal (ULN) range) as documented by at least three values: one taken 28-52 weeks before baseline visit, one taken 6 to 24 weeks before the baseline visit, & the final value within 6 weeks prior to baseline visit.
- No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening visit (up to 6 weeks prior to baseline visit). a. Participants who meet American Association for the Study of Liver Diseases (AASLD) criteria for HCC surveillance must have negative liver imaging as shown by ultrasound, computerized tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to baseline visit. b. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging & shown not to have HCC on CT or MRI before they can be enrolled.
Exclusion Criteria:
- History of hepatic decompensation
- Evidence of decompensated liver disease prior to or during screening, including direct bilirubin >0.5 mg/dL, international normalization ratio (INR) >1.5, or serum albumin <3.5 g/dL.
- Platelet count <120,000/mm3, hemoglobin <13 g/dL (males) or <12 g/dL (females), absolute neutrophil count < 1500 /mm3 (<1000/mm3 for African-Americans) at last screening visit.
- Previous treatment with medications that have established activity against HBV including interferon & nucleos(t)ide analogs ≥24 weeks. Patients with <24 weeks of prior HBV treatment & a wash-out period >24 weeks are not excluded.
- Known allergy or intolerance to study medications.
- Females who are pregnant or breastfeeding. Females of childbearing potential unable or unwilling to use a reliable method of contraception during the treatment period.
- Renal insufficiency with calculated creatinine clearance <50 mL/min at screening.
- History of alcohol or drug abuse within 48 weeks of baseline visit.
- Previous liver or other organ transplantation (including engrafted bone marrow).
- Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty liver disease (NAFLD) with steatosis &/or mild to moderate steatohepatitis is acceptable but NAFLD with severe steatohepatitis is exclusionary.
- Presence of anti-hepatitis D virus (HDV) or anti-hepatitis C virus (HCV) (unless HCV RNA negative) in serum on any occasion in the 144 weeks prior to baseline visit. Presence of anti-HIV (test completed within 6 weeks prior to baseline visit).
- Pre-existing psychiatric condition(s), including, but not limited to: current moderate or severe depression, history of depression requiring hospitalization within the past 10 years, history of suicidal or homicidal attempt within the past 10 years, history of severe psychiatric disorders as determined by a study physician.
- History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.
- Any medical condition that would, in the opinion of a study physician, be predicted to be exacerbated by therapy or that would limit study participation.
- Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study.
- Evidence of active or suspected malignancy, or a history of malignancy within the 144 weeks prior to baseline visit (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
- Expected need for ongoing use of any antivirals with activity against HBV during the course of the study.
- Concomitant use of complementary or alternative medications purported to have antiviral activity.
- Participation in any other clinical trial involving investigational drugs within 30 days of the baseline visit or intention to participate in another clinical trial involving investigational drugs during participation in this study.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Peginterferon and entecavir
A combination of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon.
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Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Forekomst af alvorlige bivirkninger (SAE) pr. person-år
Tidsramme: Fra første behandling til slutningen af behandlingen (op til 48 uger) og slutningen af opfølgningen (op til 96 uger)
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Incidensen beregnes som antallet af SAE divideret med antallet af personår med observation, som er summen, på tværs af alle deltagere, af antallet af år mellem behandlingsstart og afslutning af behandling, eller slutningen af opfølgningen. -op, hhv.
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Fra første behandling til slutningen af behandlingen (op til 48 uger) og slutningen af opfølgningen (op til 96 uger)
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Proportion of Participants With HBeAg Loss (Lack of Detectable HBeAg) AND HBV DNA ≤1,000 IU/mL
Tidsramme: End of follow-up (up to 96 weeks)
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Lack of data was considered to be treatment failure.
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End of follow-up (up to 96 weeks)
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Incidence of Adverse Events (AEs) Per Person-Year of Observation
Tidsramme: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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The number of AEs includes both AEs and Serious Adverse Events (SAEs).
The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.
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From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Andel af deltagere med HBeAg serokonvertering
Tidsramme: Afslutning af behandlingen (op til 48 uger)
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Afslutning af behandlingen (op til 48 uger)
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Andel af deltagere med HBeAg serokonvertering
Tidsramme: Slut på opfølgning (op til 96 uger)
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Slut på opfølgning (op til 96 uger)
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Andel af deltagere med HBsAg serokonvertering
Tidsramme: Afslutning af behandlingen (op til 48 uger)
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Afslutning af behandlingen (op til 48 uger)
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Andel af deltagere med HBsAg serokonvertering
Tidsramme: Slut på opfølgning (op til 96 uger)
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Slut på opfølgning (op til 96 uger)
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Andel af deltagere med HBV-DNA ≤1000 IE/ml
Tidsramme: Afslutning af behandlingen (op til 48 uger)
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Afslutning af behandlingen (op til 48 uger)
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Andel af deltagere med HBV-DNA ≤1000 IE/ml
Tidsramme: Slut på opfølgning (op til 96 uger)
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Slut på opfølgning (op til 96 uger)
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Proportion of Participants With HBeAg Loss
Tidsramme: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBeAg Loss
Tidsramme: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBsAg Loss
Tidsramme: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBsAg Loss
Tidsramme: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With Alanine Aminotransferase (ALT) <45 U/L for Men, <30 U/L for Women
Tidsramme: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT <45 U/L for Men, <30 U/L for Women
Tidsramme: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
Tidsramme: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With ALT Normalization (Men <30 U/L, Women <20 U/L)
Tidsramme: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
Tidsramme: End of treatment (up to 48 weeks)
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End of treatment (up to 48 weeks)
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Proportion of Participants With HBV DNA <20 IU/mL
Tidsramme: End of follow-up (up to 96 weeks)
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End of follow-up (up to 96 weeks)
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Absence of Detectable Antiviral Drug-resistance HBV Mutations
Tidsramme: End of treatment (up to 48 weeks)
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HBV drug resistance variant testing was performed at the CDC laboratory.
The sequences of the HBV polymerase spanning nucleotide positions 311-1021 were determined by Sanger sequencing.
Drug resistance mutations that were tested in this study included L80VI, L82M, T128N, W153Q, F166L, I169T, V173L, L180M, A181TV, T184ACFGILMS, V191T, A194T, A200V, S202ETV, M204IV, V207I, N236T, M250ILV, and G145R.
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End of treatment (up to 48 weeks)
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Samarbejdspartnere og efterforskere
Efterforskere
- Studiestol: Averell Sherker, MD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Ledende efterforsker: Anna Lok, MD, University of Michigan
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i fordøjelsessystemet
- RNA-virusinfektioner
- Virussygdomme
- Infektioner
- Blodbårne infektioner
- Overførbare sygdomme
- Leversygdomme
- Hepatitis, viral, menneskelig
- Hepadnaviridae infektioner
- DNA-virusinfektioner
- Enterovirus infektioner
- Picornaviridae infektioner
- Hepatitis, kronisk
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, kronisk
- Anti-infektionsmidler
- Antivirale midler
- Peginterferon alfa-2a
- Entecavir
Andre undersøgelses-id-numre
- DK082864 HBRN IT Adult Trial
- UL1RR024986 (U.S. NIH-bevilling/kontrakt)
- UL1TR001111 (U.S. NIH-bevilling/kontrakt)
- U01DK082916 (U.S. NIH-bevilling/kontrakt)
- U01DK082864 (U.S. NIH-bevilling/kontrakt)
- U01DK082874 (U.S. NIH-bevilling/kontrakt)
- U01DK082944 (U.S. NIH-bevilling/kontrakt)
- U01DK082843 (U.S. NIH-bevilling/kontrakt)
- U01DK082871 (U.S. NIH-bevilling/kontrakt)
- UL1TR000004 (U.S. NIH-bevilling/kontrakt)
- A-DK-3002-001 (Andet bevillings-/finansieringsnummer: Interagency agreement with NIDDK)
- U01DK082863 (U.S. NIH-bevilling/kontrakt)
- U01DK082866 (U.S. NIH-bevilling/kontrakt)
- U01DK082867 (U.S. NIH-bevilling/kontrakt)
- U01DK082872 (U.S. NIH-bevilling/kontrakt)
- U01DK082919 (U.S. NIH-bevilling/kontrakt)
- U01DK082923 (U.S. NIH-bevilling/kontrakt)
- U01DK082927 (U.S. NIH-bevilling/kontrakt)
- U01DK082943 (U.S. NIH-bevilling/kontrakt)
- UL1TR000058 (U.S. NIH-bevilling/kontrakt)
- P30DK050306 (U.S. NIH-bevilling/kontrakt)
- M01RR000040 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
IPD-delingsadgangskriterier
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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Kliniske forsøg med Hepatitis B
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The Affiliated Nanjing Drum Tower Hospital of Nanjing...Gilead SciencesIkke rekrutterer endnu
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Tongji HospitalChia Tai Tianqing Pharmaceutical Group Co., Ltd.UkendtKronisk hepatitis b
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National Taiwan University HospitalChiayi Christian Hospital; E-DA Hospital; Taipei City Hospital; Taipei Tzu... og andre samarbejdspartnereRekrutteringKronisk hepatitis b | Reaktivering af hepatitis BTaiwan
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Mahidol UniversityUkendtKronisk Hepatitis B, HBsAg, Hepatitis B-vaccineThailand
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Tongji HospitalGilead SciencesRekruttering
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Jiangsu HengRui Medicine Co., Ltd.Ukendt
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Changhai HospitalAfsluttet
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Brii Biosciences LimitedVir Biotechnology, Inc.Aktiv, ikke rekrutterendeKronisk hepatitis B-virusinfektionSingapore, Thailand, Australien, Kina, Korea, Republikken
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Nanfang Hospital of Southern Medical UniversityRekruttering
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IlDong Pharmaceutical Co LtdRekrutteringKronisk hepatitis bKorea, Republikken
Kliniske forsøg med Entecavir and peginterferon
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National Institute of Diabetes and Digestive and...AfsluttetEntecavir/pegyleret interferon hos immuntolerante børn med kronisk hepatitis B-virus (HBV) infektionHepatitis BForenede Stater, Canada
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Third Affiliated Hospital, Sun Yat-Sen UniversityAfsluttetAntiviral Treatment of Chronic Hepatitis B
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Hoffmann-La RocheTrukket tilbage
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National Taiwan University HospitalRoche Pharma AGUkendtKronisk hepatitis BTaiwan
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National Taiwan University HospitalNational Science Council, TaiwanUkendtHepatitis B, kroniskTaiwan
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National Taiwan University HospitalBristol-Myers SquibbUkendtKronisk hepatitis BTaiwan
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Beijing 302 HospitalUkendt
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National Taiwan University HospitalNational Science Council, TaiwanUkendtHepatitis B, kroniskTaiwan
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Ziv HospitalUkendt
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Gangnam Severance HospitalRoche Pharma AGUkendt