- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00307242
Study Comparing the Safety of Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir Before Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B
A Single Center Open-Label, Randomized Study Comparing the Safety of Immediately Switching From Lamivudine to Adefovir Dipivoxil Versus Overlapping Lamivudine and Adefovir for 12 Weeks Before Instituting Adefovir Dipivoxil Monotherapy in Patients With Chronic Hepatitis B
In earlier clinical studies, when patients who have been on lamivudine (LAM) were switched to adefovir dipivoxil (ADV), some patients developed ALT flares with an elevation of ALT > 10 x the upper limits of normal (ULN).
There were no cases of hepatic decompensation with the flares, however. The transition methods were varied among physicians from no overlapping to overlapping for 1 to 3 months with LAM and ADV. There is still some uncertainty about the optimal approach to switching from LAM to ADV.
This study will compare the safety of directly switching to ADV to a protocolled switch after a period of overlap of 12 weeks. This will facilitate pro-active switching in patients on LAM and will also highlight genotypic resistance ahead of phenotypic resistance as a reason to switch patients. Data to date have only been presented as part of a controlled study in patients with clinically evident LAM-resistance. This study will enroll patients who still have serum hepatitis B virus (HBV) DNA suppression whilst receiving LAM.
Panoramica dello studio
Descrizione dettagliata
Chronic HBV infection is an important worldwide cause of morbidity, mortality and source of potential new infections. There are an estimated 350 million carriers of HBV in the world. In China, Southeast Asia and sub-Saharan Africa, as many as 10-15% of the population are chronically infected. In North America and Northern Europe, infection and carrier rates are much lower, usually below 1%. Intermediate carrier rates of 1-5% are found in Southern Europe (e.g., Italy, Greece and Spain), parts of South and Central America, the Middle East and Japan. Persistent infection develops in over 90% of perinatally infected children and in 3-10% of people who become infected after the age of 6 years. Worldwide, it has been estimated that more than one million people die annually due to HBV-related end stage diseases such as cirrhosis and hepatocellular carcinoma.
The goal of antiviral therapy for hepatitis B is to reduce a patient's risks for progressive liver disease through prolonged suppression or eradication of HBV infection and to arrest or ameliorate HBV-related liver damage.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 4
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Males and females ≥ 18 years of age with chronic hepatitis B
- Hepatitis B surface antigen (HBsAg)(+) for a minimum of 6 months prior to entry
- Hepatitis B envelope antigen (HBeAg)(+) or (-) at baseline
- Patients having previously received LAM for at least 24 weeks
- Patients with compensated liver function (Child-Pugh score ≤ 6)
Exclusion Criteria:
- Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol.
- Received immunoglobulins, interferon or other immune or cytokine-based therapies with possible activity in hepatitis B disease within 6 months prior to study screening.
- Organ or bone marrow transplant recipients.
- Evidence of active liver disease due to other causes (e.g., Wilson's disease, hemochromatosis, autoimmune hepatitis, hepatitis C or hepatitis D co-infection)
- Patients taking parenteral (intravenous or intramuscular or subcutaneous) or oral steroids, immuno-suppressant therapies or chemotherapeutic agents within 2 months of study screening or expected to receive these agents during the course of the study.
- Previous participation in an investigational trial involving administration of any investigational compound within 2 months prior to the study screening or those who received anti-HBV therapy other than lamivudine within the previous 3 months (e.g. anabolic steroids, ketaconazole, itraconazole, isoniazid, rifampin, rifabutin, simvastatin, lovastatin)
- Clinically relevant alcohol or drug use or history of alcohol or drug use considered by the investigator to be sufficient to hinder compliance with treatment, follow up procedures or evaluation of adverse events
- Lactating females or females with a positive serum pregnancy test.
- Females of childbearing potential (post-puberty) unwilling or unable to have pregnancy testing at any study visit
- Therapy with nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin pentamidine, tacrolimus, cyclosporine) or competitors of renal excretion (e.g. probenecid) within 2 months prior to study screening or the expectation that subject will receive these during the course of the study.
- The use of antiviral therapy with agents demonstrating potential anti-HBV activity other than lamivudine within the previous 3 months (e.g. famciclovir, lobucavir, emtricitabine, DAPD, L-FMAU, entecavir, ganciclovir or others).
- History of hypersensitivity to nucleoside and/or nucleotide analogues.
- Clinical, ultrasonographic or radiologic evidence of hepatic mass suggestive of hepatocellular carcinoma.
- Serum alphafetoprotein (AFP) > 50 ng/mL at the first screening visit. However, if the AFP level is > 50 ng/mL at the first screening visit, but has remained stable or decreased over the 6 months preceding the first screening visit, and if there is no radiologic or ultrasonic evidence of hepatic mass(es) suggestive of hepatocellular carcinoma, the patient will be allowed to enroll.
- Inability to comply with study requirements.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Comparatore attivo: Direct switch to Adefovir Dipivoxil from Lamivudine
|
|
Comparatore attivo: Overlapping Lamivudine and Adefovir Dipivoxil for 3 months followed by ADV monotherapy
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
---|---|
Observe the proportion of patients with ALT elevations (> 10 x ULN) at any time over the course of the switch
Lasso di tempo: baseline, 3, 6, 9, and 12 months
|
baseline, 3, 6, 9, and 12 months
|
Study serum HBV DNA levels over time
Lasso di tempo: baseline, 3, 6, 9, and 12 months
|
baseline, 3, 6, 9, and 12 months
|
Study serum ALT levels over time
Lasso di tempo: baseline, 3, 6, 9, and 12 months
|
baseline, 3, 6, 9, and 12 months
|
Study the proportion of patients with YMDD variants at entry
Lasso di tempo: baseline, 3, 6, 9, and 12 months
|
baseline, 3, 6, 9, and 12 months
|
Study the safety during the switching period
Lasso di tempo: baseline, 3, 6, 9, and 12 months
|
baseline, 3, 6, 9, and 12 months
|
Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Hie-Won Hann, M.D., Thomas Jefferson University
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie dell'apparato digerente
- Infezioni da virus a RNA
- Malattie virali
- Infezioni
- Infezioni a trasmissione ematica
- Malattie trasmissibili
- Malattie del fegato
- Epatite, virale, umana
- Infezioni da Hepadnaviridae
- Infezioni da virus del DNA
- Infezioni da enterovirus
- Infezioni da Picornaviridae
- Epatite B
- Epatite
- Epatite A
- Epatite B, cronica
- Epatite cronica
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti antivirali
- Inibitori della trascrittasi inversa
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Adefovir
- Adefovir dipivoxil
Altri numeri di identificazione dello studio
- 05U.164
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Epatite cronica B
-
Northwestern UniversityNational Cancer Institute (NCI)Attivo, non reclutanteLinfoma diffuso a grandi cellule B | Linfoma diffuso a grandi cellule B, non altrimenti specificato | Linfoma a cellule B di alto grado, non altrimenti specificato | Linfoma a grandi cellule B ricco di cellule T/istiociti | Linfoma a cellule B di alto grado con riarrangiamenti di MYC e BCL2... e altre condizioniStati Uniti
-
Nathan DenlingerBristol-Myers SquibbReclutamentoLinfoma non Hodgkin a cellule B ricorrente | Linfoma diffuso a grandi cellule B-ricorrente | Linfoma follicolare ricorrente | Linfoma ricorrente a cellule B di alto grado | Linfoma primario mediastinico a grandi cellule B-ricorrente | Linfoma non Hodgkin indolente a cellule B trasformato in linfoma... e altre condizioniStati Uniti
-
National Cancer Institute (NCI)Attivo, non reclutanteLinfoma diffuso ricorrente a grandi cellule B Tipo a cellule B attivato | Linfoma diffuso a grandi cellule B refrattario Tipo di cellule B attivatoStati Uniti, Arabia Saudita
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); AmgenAttivo, non reclutanteLinfoma diffuso ricorrente a grandi cellule B | Linfoma diffuso a grandi cellule B refrattario | CD20 Positivo | Linfoma diffuso a grandi cellule B stadio I | Linfoma diffuso a grandi cellule B stadio II | Linfoma diffuso a grandi cellule B stadio III | Linfoma diffuso a grandi cellule B stadio IVStati Uniti
-
University of NebraskaBristol-Myers SquibbReclutamentoLinfoma follicolare | Linfoma non Hodgkin refrattario | Linfoma a cellule B di alto grado | DLBCL - Linfoma diffuso a grandi cellule B | Linfoma non Hodgkin recidivato | Linfoma mediastinico a grandi cellule B | Linfoma non Hodgkin a cellule B indolenteStati Uniti
-
Curocell Inc.ReclutamentoLinfoma a cellule B di alto grado | Linfoma diffuso a grandi cellule B (DLBCL) | Linfoma primario a grandi cellule B del mediastino (PMBCL) | Linfoma follicolare trasformato (TFL) | Linfoma refrattario a grandi cellule B | Linfoma a grandi cellule B recidivatoCorea, Repubblica di
-
Lapo AlinariReclutamentoLinfoma ricorrente a cellule B di alto grado con riarrangiamenti di MYC, BCL2 e BCL6 | Linfoma refrattario a cellule B di alto grado con riarrangiamenti di MYC, BCL2 e BCL6 | Linfoma ricorrente a cellule B di alto grado con riarrangiamenti di MYC e BCL2 o BCL6 | Linfoma refrattario a cellule... e altre condizioniStati Uniti
-
Ohio State University Comprehensive Cancer CenterReclutamentoLinfoma diffuso a grandi cellule B | Linfoma a cellule B di alto grado | Linfoma diffuso a grandi cellule B, non altrimenti specificato | Linfoma diffuso a grandi cellule B Tipo di cellule B del centro germinaleStati Uniti
-
First Affiliated Hospital Xi'an Jiaotong UniversityEureka Therapeutics Inc.SconosciutoLinfoma CD19+, cellule B | Leucemia CD19+, cellule BCina
-
Athenex, Inc.ReclutamentoLinfoma a cellule B | CLL/SLL | TUTTI, Infanzia | DLBCL - Linfoma diffuso a grandi cellule B | Leucemia a cellule B | NHL, recidivato, adulto | ALL, cellula B adultaStati Uniti
Prove cliniche su Adefovir Dipivoxil
-
Bukwang PharmaceuticalCompletato
-
Gilead SciencesApprovato per il marketing
-
GlaxoSmithKlineCompletato
-
Jun ChengSanofi; Fujian Cosunter Pharmaceutical Co. LtdSconosciuto
-
GlaxoSmithKlineCompletatoFibrosi | Epatite cronica B | Epatite B, cronica | CirrosiTaiwan, Corea, Repubblica di, Singapore, Hong Kong, Vietnam
-
GlaxoSmithKlineCompletatoEpatite cronica B | Epatite B, cronicaCorea, Repubblica di
-
National Institute of Allergy and Infectious Diseases...CompletatoInfezioni da HIV | Epatite cronica BStati Uniti
-
NovartisNovartis PharmaceuticalsCompletatoEpatite cronica BAustralia, Canada, Francia, Stati Uniti, Taiwan, Corea, Repubblica di, Singapore, Tailandia, Cina
-
Third Affiliated Hospital, Sun Yat-Sen UniversityGuangdong Provincial People's Hospital; Guangzhou 8th People's HospitalCompletato