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Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection

30. januar 2014 opdateret af: Sang Hoon Ahn, Yonsei University

A Multicenter, Open-label, Prospective Study to Evaluate Antiviral Efficacy and Safety of Entecavir Plus Tenofovir Combination in Subjects With Multi-drug Resistant Chronic Hepatitis B Virus Infection

Entecavir(ETV) plus Tenofovir Disoproxil Fumarate(TDF) combination will show effective antiviral activity and prevent further development of antiviral resistance in hepatitis B e antigen(HBeAg)-positive or -negative Chronic Hepatitis B(CHB) patients who experienced multidrug resistance

All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

Studieoversigt

Status

Ukendt

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

  1. It has been one of unsolved issues and unmet needs in CHB management to develop an optimal combination regimen to manage multidrug resistant HBV characterized by selection of variants with two or more classes A of signature genotypic resistant mutations1-3
  2. Currently adding on Adefovir(ADV) has been generally recommended in Lamivudine(LAM)- or Telbivudine(LdT)-resistant patients but little is known about the optimal management of CHB patients who developed multidrug resistance4
  3. Recent report has shown that the combination of LAM plus ADV did not suppress HBV DNA effectively in CHB patients with resistance mutations to both drugs. Only 12.2% of these pts achieved virologic response(VR; HBV DNA <60 IU/mL) at 12 months and multivariable analysis showed that LAM+ADV group and the presence of the rtA181V/T mutation were independently associated with a decreased rate of virologic response (HBV DNA <2,000 IU/ml) at 12 months4
  4. ETV has been demonstrated to be effective in patients with ADV resistance but not in patients with proven YMDD mutation. In contrast, TDF has been shown to be effective in patients with YMDD mutation but not necessarily in all patients with ADV resistance.1-3
  5. Thus theoretically, the combination of the most potent nucleoside analogue and nucleotide analogue with non-overlapping resistance profiles, such as ETV plus TDF, is expected to be a promising salvage treatment for multidrug resistant HBV but clinical evidence is limited
  6. Therefore, this study will explore that adequate management of multidrug resistant patients using ETV plus TDF combination may lead to faster and greater viral suppression and prevent further emergence of antiviral resistance

All subjects will orally take investigational drugs once daily for 48 weeks. All subjects will be assessed at baseline, Week 4, 12, 24, 36 and 48. Evaluations at each visit will include vital signs, physical examinations, laboratory tests and HBV DNA levels. They were also questioned about adverse events and concomitant medications. At baseline and every six months thereafter, serum will be assayed for HBV serology. Genotypic analysis will be performed at baseline and 48 weeks.

Undersøgelsestype

Interventionel

Tilmelding (Forventet)

90

Fase

  • Fase 4

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

20 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. ≥ 20 years of age
  2. History of HBsAg positive for more than 6 months
  3. Subject who has a history of genotypic resistance to NAs from two different classes A
  4. Detectable HBV DNA (≥ 60 IU/mL) while on any rescue treatment regimen for at least 24 weeks
  5. HBeAg-positive and -negative
  6. Compensated liver disease (Child-Pugh A)
  7. Signed written informed consent after being instructed about the objective and procedure of the clinical study

Exclusion Criteria:

  1. Subjects with Alanine Aminotransferase(ALT) > 10xUpper Limit of normal(ULN)
  2. Co-infected with hepatitis C virus(HCV) or HIV
  3. Pregnant or lactating woman
  4. 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
  5. History of liver transplantation or planned for liver transplantation
  6. Subject who was diagnosed malignant tumor and has been receiving chemotherapy
  7. Subject who has hepatocellular carcinoma(HCC) history or who shows potential HCC finding such as suspicious region in the radiologic exam(abdominal US or CT) or serum Alpha Feto Protein(AFP) elevation
  8. Renal Insufficiency (CLcr < 50ml/min based on Cockcroft-Gault equation considering weight, ages and serum creatinine)
  9. Patient 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.)
  10. Subject who has a history of hypersensitivity to study drug or its ingredients
  11. Subject who is involved in other clinical trial within 60 days prior to study entry
  12. Subject who the investigator deems inappropriate to participate in this study

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

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
Eksperimentel: Entecavir 1.0mg + Tenofovir 300mg
All subjects will orally take investigational drugs once daily for 48 weeks.
Medicin: Entecavir + Tenofovir (MDR group)
Entecavir 1.0mg + Tenofovir 300mg
Andre navne:
  • Entecavir 1.0mg - Braclude
  • Tenofovir 300mg - Viread

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
The proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time PCR at Week 48
Tidsramme: at Week 48
To evaluate the proportion of subjects who achieve virologic response(HBV DNA < 60 IU/mL, approximately 300 copies/mL) by real-time Polymerase chain reaction(PCR) at Week 48 after Entecavir plus Tenofovir combination therapy
at Week 48

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Virologic, serologic, biochemical efficacy and safety profile, as measured by the incidence of clinical adverse events and laboratory abnormalities including renal marker
Tidsramme: Week 4, 12, 24, 36, and 48
To evaluate virologic, serologic and biochemical response and safety of Entecavir plus Tenofovir combination therapy for 48 weeks
Week 4, 12, 24, 36, and 48

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Yonsei University

Samarbejdspartnere

Bristol-Myers Squibb
Seoul St. Mary's Hospital
The Catholic University of Korea

Efterforskere

  • Ledende efterforsker: Sang Hoon Ahn, MD, PhD, Yonsei University

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. august 2012

Primær færdiggørelse (Forventet)

1. april 2014

Studieafslutning (Forventet)

1. april 2014

Datoer for studieregistrering

Først indsendt

7. maj 2012

Først indsendt, der opfyldte QC-kriterier

8. maj 2012

Først opslået (Skøn)

9. maj 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

31. januar 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

30. januar 2014

Sidst verificeret

1. januar 2014

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • AI463-273

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Kronisk hepatitis B

Kliniske forsøg med Entecavir + Tenofovir (MDR group)

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in India

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner