Safety and Efficacy Study of LB80380 in the Patients With Lamivudine-Refractory Chronic Hepatitis B
A PhaseII, Open-Label, Multinational, Multi-Centre, Sequential Group, Dose-Escalation Study to Assess the Safety and Antiviral Activity of LB80380 for 12 Weeks in Patients With Lamivudine-Refractory Chronic Hepatitis B
Studieoversigt
Detaljeret beskrivelse
LB80380, an oral prodrug, is a promising candidate nucleoside analogue with antiviral activity against wild-type HBV. LB80380 is undergoing clinical development by LG Life Sciences for use in the treatment of chronic HBV infection and for treatment of lamivudine-resistant disease.
In this study, the treatment period was divided into two parts: a 4-week treatment period with dose escalation assessment (Part 1), followed by an 8-week extension period (Part 2).
During Part 1, patients received LB80380 and LVD 100 mg once daily for 4 weeks. Each patient was then given only LB80380 for an additional 8 weeks (Part 2) unless dose-limiting toxicity (DLT) was observed during Part 1. At each dose level, all patients were to complete at least Part 1 of the treatment period before enrolment into the next Dose Group could commence. Dose escalation to the next group was not to be initiated if more than two patients experienced DLT during Part 1 in the previous Dose Group. Additionally, patients enrolled in LB80380 150mg and 240mg groups who agreed to participate in the pharmacokinetic (PK) analyses visited the study site the day before Week 12 for blood sampling. Follow-up period was 24 weeks, and patients were treated with adefovir dipivoxil during the follow-up period. During the study, patients were evaluated for changes from baseline in serum HBV DNA. Safety was evaluated on the basis of occurrence of AEs and changes from baseline in clinical laboratory parameters, physical examination findings, and vital signs.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
-
Hong Kong, Kina
- Queen Mary Hospital
-
-
-
-
-
Seoul, Korea, Republikken
- Korea University Medical Center
-
Seoul, Korea, Republikken
- Severance Hospital of Yonsei University
-
Seoul, Korea, Republikken
- The Catholic University of Korea, Kangnam St. Mary's Hospital
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Compensated chronic hepatitis B patient
- Presence of serum HBsAg for more than 6 months.
- Presence of HBeAg for more than 1 month with compensated liver disease
- Confirmation of YMDD mutants (M552V, M552I and its related double mutant at L528M) by genotyping of the YMDD motif using line probe assay (INNO-LiPA HBV DR assay)
- Screening HBV DNA value higher than or equal to 1,000,000 copies/mL (measured by the COBAS Amplicor HBV Monitor™ assay)
- Screening ALT value between 1.5 and 10 x ULN
Exclusion Criteria:
- Co-infection with hepatitis C or D virus (HCV or HDV) or HIV
- Pregnancy or breast-feeding
- Previous treatment with nucleoside analogue or any other treatment for HBV except for lamivudine within 6 months prior to study entry
- Treatment with immunomodulatory agent or corticosteroids within 6 months prior to study entry.
- De-compensated liver disease
- Screening alpha-fetoprotein (AFP) value > 20 ng/mL, and a follow-up ultrasonography performed prior to baseline shows findings indicative of HCC.
- Presence of anti-HBs at screening
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: LB80380 30mg
|
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
|
|
Eksperimentel: LB80380 60mg
|
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
|
|
Eksperimentel: LB80380 90mg,
LB80380 90mg
|
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
|
|
Eksperimentel: LB80380 150mg
|
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
|
|
Eksperimentel: LB80380 240mg
|
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Mean serum HBV DNA level (log10) reduction from the baseline at Week 12
Tidsramme: Week 12
|
Week 12
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Proportion of patients with HBeAg seroconversion at 12 weeks Proportion of patients with HBsAg seroconversion at 12 weeks Proportion of patients with ALT normalization at 12 weeks Safety assessment during the whole study period
Tidsramme: Week 12
|
Week 12
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Ching-Lung Lai, Dr, Queen Mary Hospital, Hong Kong
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 (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
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 B
- Hepatitis
- Hepatitis A
- Hepatitis B, kronisk
- Hepatitis, kronisk
Andre undersøgelses-id-numre
- BVCL004
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 .