- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01369199
Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B (HBRN)
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert 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).
Studietype
Registrering (Faktiske)
Fase
- Fase 3
Kontakter og plasseringer
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, Forente stater, 90095
- University of California Los Angeles
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Los Angeles, California, Forente stater, 90048
- Cedars Sinai Medical Center
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San Francisco, California, Forente stater, 94143
- University of California San Francisco
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San Francisco, California, Forente stater, 94115
- California Pacific Medical Center
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Hawaii
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Honolulu, Hawaii, Forente stater, 96813
- Queen's Medical Center
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Maryland
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Bethesda, Maryland, Forente stater, 20892
- NIH Clinical Center
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Massachusetts
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Boston, Massachusetts, Forente stater, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Forente stater, 02114
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Forente stater, 48109
- University of Michigan Health System
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Minnesota
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Minneapolis, Minnesota, Forente stater, 55446
- University of Minnesota
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Rochester, Minnesota, Forente stater, 55905
- Mayo Clinic
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Missouri
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Saint Louis, Missouri, Forente stater, 63110
- Washington University
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Saint Louis, Missouri, Forente stater, 63104
- Saint Louis University
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North Carolina
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Chapel Hill, North Carolina, Forente stater, 27599
- University of North Carolina
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Durham, North Carolina, Forente stater, 27710
- Duke University Medical Center
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Texas
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Dallas, Texas, Forente stater, 75390
- University of Texas Southwestern
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Dallas, Texas, Forente stater, 75246
- Baylor University Medical Center
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Virginia
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Richmond, Virginia, Forente stater, 23498
- Virginia Commonwealth University
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Washington
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Seattle, Washington, Forente stater, 98101
- Virginia Mason Medical Center
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Seattle, Washington, Forente stater, 98105
- University of Washington Medical Center
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
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 studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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 navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Forekomst av alvorlige bivirkninger (SAE) per person-år
Tidsramme: Fra første behandling til slutten av behandlingen (opptil 48 uker) og slutten av oppfølgingen (opptil 96 uker)
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Forekomsten beregnes som antall SAE delt på antall personår med observasjon, som er summen, på tvers av alle deltakere, av antall år mellom behandlingsstart og behandlingsslutt, eller slutten av oppfølgingen. - opp, henholdsvis.
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Fra første behandling til slutten av behandlingen (opptil 48 uker) og slutten av oppfølgingen (opptil 96 uker)
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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 |
Tiltaksbeskrivelse |
Tidsramme |
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Andel deltakere med HBeAg serokonvertering
Tidsramme: Slutt på behandling (opptil 48 uker)
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Slutt på behandling (opptil 48 uker)
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Andel deltakere med HBeAg serokonvertering
Tidsramme: Slutt på oppfølging (opptil 96 uker)
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Slutt på oppfølging (opptil 96 uker)
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Andel deltakere med HBsAg serokonvertering
Tidsramme: Slutt på behandling (opptil 48 uker)
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Slutt på behandling (opptil 48 uker)
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Andel deltakere med HBsAg serokonversjon
Tidsramme: Slutt på oppfølging (opptil 96 uker)
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Slutt på oppfølging (opptil 96 uker)
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Andel deltakere med HBV-DNA ≤1000 IE/mL
Tidsramme: Slutt på behandling (opptil 48 uker)
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Slutt på behandling (opptil 48 uker)
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Andel deltakere med HBV-DNA ≤1000 IE/mL
Tidsramme: Slutt på oppfølging (opptil 96 uker)
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Slutt på oppfølging (opptil 96 uker)
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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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Samarbeidspartnere og etterforskere
Etterforskere
- Studiestol: Averell Sherker, MD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Hovedetterforsker: Anna Lok, MD, University of Michigan
Publikasjoner og nyttige lenker
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- RNA-virusinfeksjoner
- Virussykdommer
- Infeksjoner
- Blodbårne infeksjoner
- Smittsomme sykdommer
- Leversykdommer
- Hepatitt, viral, menneskelig
- Hepadnaviridae-infeksjoner
- DNA-virusinfeksjoner
- Enterovirusinfeksjoner
- Picornaviridae-infeksjoner
- Hepatitt, kronisk
- Hepatitt B
- Hepatitt
- Hepatitt A-virus
- Hepatitt B, kronisk
- Anti-infeksjonsmidler
- Antivirale midler
- Peginterferon alfa-2a
- Entecavir
Andre studie-ID-numre
- DK082864 HBRN IT Adult Trial
- UL1RR024986 (U.S. NIH-stipend/kontrakt)
- UL1TR001111 (U.S. NIH-stipend/kontrakt)
- U01DK082916 (U.S. NIH-stipend/kontrakt)
- U01DK082864 (U.S. NIH-stipend/kontrakt)
- U01DK082874 (U.S. NIH-stipend/kontrakt)
- U01DK082944 (U.S. NIH-stipend/kontrakt)
- U01DK082843 (U.S. NIH-stipend/kontrakt)
- U01DK082871 (U.S. NIH-stipend/kontrakt)
- UL1TR000004 (U.S. NIH-stipend/kontrakt)
- A-DK-3002-001 (Annet stipend/finansieringsnummer: Interagency agreement with NIDDK)
- U01DK082863 (U.S. NIH-stipend/kontrakt)
- U01DK082866 (U.S. NIH-stipend/kontrakt)
- U01DK082867 (U.S. NIH-stipend/kontrakt)
- U01DK082872 (U.S. NIH-stipend/kontrakt)
- U01DK082919 (U.S. NIH-stipend/kontrakt)
- U01DK082923 (U.S. NIH-stipend/kontrakt)
- U01DK082927 (U.S. NIH-stipend/kontrakt)
- U01DK082943 (U.S. NIH-stipend/kontrakt)
- UL1TR000058 (U.S. NIH-stipend/kontrakt)
- P30DK050306 (U.S. NIH-stipend/kontrakt)
- M01RR000040 (U.S. NIH-stipend/kontrakt)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
Tilgangskriterier for IPD-deling
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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