Hepatitis B Clinical Trial
Official title:
A Phase 3b, Randomized, Double-Blind, Double-Dummy Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus Emtricitabine Plus Tenofovir DF Fixed-Dose Combination Therapy in Subjects With Chronic Hepatitis B Who Are Resistant to Lamivudine
Verified date | February 2016 |
Source | Gilead Sciences |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Food and Drug Administration |
Study type | Interventional |
The aim of therapy for the treatment of chronic hepatitis B virus (HBV) is to maintain
suppression of viral replication to prevent the emergence of complications, which requires
long-term therapy. Durable suppression of viral replication is achieved in the treatment of
chronic viral diseases by preventing of the emergence of drug-resistant mutations. The
clinical guidelines for the management of lamivudine resistant patients are variable. Some
recommend switching to another agent without cross-resistance, while others recommend adding
on another agent without cross-resistance. Limited clinical data exists to demonstrate
whether tenofovir disoproxil fumarate (tenofovir DF; TDF) is an effective monotherapy for
lamivudine resistant patients or if it should be used as part of a combination therapy
regimen.
This study is designed to evaluate the effectiveness, safety, and tolerability of tenofovir
DF monotherapy versus emtricitabine (FTC)/tenofovir DF combination therapy in participants
with chronic HBV with lamivudine resistance (presence of the rtM204I/V mutation with or
without the rtL180M mutation) over a 240-week period. Participants in this study must be
receiving lamivudine treatment at the time of enrollment.
Status | Completed |
Enrollment | 280 |
Est. completion date | February 2015 |
Est. primary completion date | November 2011 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 75 Years |
Eligibility |
Inclusion Criteria - Chronic HBV infection, defined as positive serum HBsAg for at least 6 months - 18 through 75 years of age, inclusive - HBV DNA = 10^3 IU/mL - Receiving treatment with lamivudine with confirmation of HBV reverse transcriptase mutation(s) known to confer resistance to lamivudine (rtM204I/V with or without rtL180M) by central laboratory assessment prior to randomization; adefovir dipivoxil treatment of = 48 weeks at the time of screening (inclusive of combination adefovir dipivoxil + lamivudine at entry) was allowed - Willing and able to provide written informed consent - Negative serum pregnancy test (for females of childbearing potential only) - Calculated creatinine clearance = 50 mL/min - Hemoglobin = 10 g/dL - Neutrophils = 1000 /mm^3 - No prior oral HBV therapy with approved nucleotide and/or nucleoside therapy or other investigational agents for HBV infection other than lamivudine or adefovir dipivoxil Exclusion Criteria - Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study - Males and females of reproductive potential who are not willing to use an effective method of contraception during the study - Alanine aminotransferase (ALT) = 10 × the upper limit of the normal range (ULN) - Decompensated liver disease - Interferon or pegylated interferon therapy within 6 months of the screening visit - Alpha fetoprotein > 50 ng/mL - Evidence of hepatocellular carcinoma - Coinfection with hepatitis C virus, HIV, or hepatitis D virus - Significant renal, cardiovascular, pulmonary, or neurological disease - Received solid organ or bone marrow transplantation - Receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion - Proximal tubulopathy - Known hypersensitivity to the study drugs, the metabolites or formulation excipients |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Gilead Sciences |
United States, Austria, Bulgaria, Canada, Czech Republic, Germany, Greece, Hungary, New Zealand, Poland, Romania, Serbia, Spain, Turkey,
Corsa AC, Liu Y, Flaherty JF, Mitchell B, Fung SK, Gane E, Miller MD, Kitrinos KM. No resistance to tenofovir disoproxil fumarate through 96 weeks of treatment in patients with lamivudine-resistant chronic hepatitis B. Clin Gastroenterol Hepatol. 2014 Dec — View Citation
Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann HW, Gurel S, Caruntu FA, Flaherty JF, Massetto B, Dinh P, Corsa A, Subramanian GM, McHutchison JG, Husa P, Gane E. Randomized comparison of tenofovir disoproxil fumarate vs emtricitabine and tenofovir dis — View Citation
Liu Y, Fung S, Gane EJ, Dinh P, Flaherty JF, Svarovskaia ES, Miller MD, Kitrinos KM. Evaluation of HBV DNA decay kinetics in patients containing both rtM204V/I mutant and wild-type HBV subpopulations during tenofovir DF (TDF) monotherapy or combination th — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of Participants With HBV DNA < 400 Copies/mL at Week 96 | Week 96 | No | |
Secondary | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 144, 192, and 240 | Weeks 48, 144, 192, and 240 | No | |
Secondary | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, 192, and 240 | Weeks 48, 96, 144, 192, and 240 | No | |
Secondary | HBV DNA Level at Weeks 48, 96, 144, 192, and 240 | Weeks 48, 96, 144, 192, and 240 | No | |
Secondary | Percentage of Participants With Normal ALT at Weeks 48, 96, 144, 192, and 240 | Normal ALT was defined as having a value less than or equal to the ULN. The ULN was 43 U/L for males and 34 U/L for females aged 18 to < 69, and 35 U/L for males and 32 U/L for females aged = 69. | Weeks 48, 96, 144, 192, and 240 | No |
Secondary | Percentage of Participants With HBeAg Loss at Weeks 48, 96, 144, 192, and 240 | The percentage of participants who were HBeAg positive at baseline and who had HBeAg Loss at the given time point was summarized. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative. | Baseline; Weeks 48, 96, 144, 192, and 240 | No |
Secondary | Percentage of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, 192, and 240 | The percentage of participants who were HBeAg positive at baseline and who had seroconversion to anti-HBe at the given time point was summarized. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive. | Baseline; Weeks 48, 96, 144, 192, and 240 | No |
Secondary | Percentage of Participants With HBV Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, 192, and 240 | The percentage of participants with HBsAg Loss at the given time point was summarized. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. | Baseline; Weeks 48, 96, 144, 192, and 240 | No |
Secondary | Percentage of Participants With Seroconversion to Antibody Against HBV Surface Antigen (Anti-HBs) at Weeks 48, 96, 144, 192, and 240 | The percentage of participants with seroconversion to anti-HBs at the given time point was summarized. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive. | Baseline; Weeks 48, 96, 144, 192, and 240 | No |
Secondary | Percentage of Participants With Virologic Breakthrough at Weeks 48, 96, 144, 192, and 240 | The percentage of participants with virologic breakthrough at the given time point was summarized. Virologic breakthrough was defined as having two consecutive 1.0 log10 or greater increases in serum HBV DNA from on-treatment nadir, or two consecutive HBV DNA values = 400 copies/mL after being < 400 copies/mL. | Baseline; Weeks 48, 96, 144, 192, and 240 | No |
Secondary | Percent Change From Baseline in Bone Mineral Density (BMD) of the Spine at Weeks 24, 48, 72, 96, 144, 192, and 240 | BMD is calculated as grams per cubic centimeter (g/cm^2); the mean (SD) percentage change is presented. | Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240 | Yes |
Secondary | Percent Change From Baseline in BMD of the Hip at Weeks 24, 48, 72, 96, 144, 192, and 240 | BMD is calculated as g/cm^2; the mean (SD) percentage change is presented. | Baseline; Weeks 24, 48, 72, 96, 144, 192, and 240 | Yes |
Secondary | Development of Drug-resistant Mutations (DRMs) | The development of DRMs was summarized, either as development of new DRMs or enrichment of existing DRMs. | Baseline to Week 240 | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01182311 -
Duration of Long-term Immunity After Hepatitis B Virus Immunization
|
||
Completed |
NCT04971928 -
Phase 1 Study of GSK3228836 Pharmacokinetics in Participants With Hepatic Impairment
|
Phase 1 | |
Completed |
NCT03285620 -
A Study of AL-034 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses in Healthy Participants
|
Phase 1 | |
Completed |
NCT01884415 -
Phase III, Study to Evaluate the Efficacy of Two Different HBV Vaccination Schemes in Patients With Hepatic Cirrhosis
|
Phase 3 | |
Recruiting |
NCT05404919 -
Utilization of Hepatitis B Virus NAT+ Donors for Hepatitis B Vaccinated Lung Transplant Candidates
|
Phase 2 | |
Completed |
NCT02153320 -
Study to Evaluate the Persistence of the Cellular and Humoral Immune Response Following Vaccinations With GlaxoSmithKline (GSK) Biologicals' Candidate Vaccines Containing HBsAg and Different Adjuvants in Healthy Adult Volunteers
|
Phase 1 | |
Completed |
NCT00352963 -
Immunogenicity & Safety Study of Combined/Separate Vaccine(s) Against Common Diseases in Infants (2,4,6 Months of Age).
|
Phase 3 | |
Completed |
NCT03567382 -
Arresting Vertical Transmission of Hepatitis B Virus
|
Phase 4 | |
Not yet recruiting |
NCT04056728 -
A Phase IV Study to Assess the Safety of EupentaTM Inj
|
Phase 4 | |
Not yet recruiting |
NCT03604016 -
Study to Assess Efficacy of Besifovir and L-carnitine in Chronic Hepatitis B Patients With Nonalcoholic Fatty Liver
|
Phase 4 | |
Completed |
NCT00753649 -
Immunogenicity and Safety of GSK Biologicals' Infanrix Hexa in Infants
|
Phase 4 | |
Recruiting |
NCT03027258 -
Point-of-Delivery Prenatal Test Results Through mHealth to Improve Birth Outcome
|
N/A | |
Completed |
NCT02540538 -
Safety and Immunogenicity of HBAI20 Hepatitis B Vaccine in Naive Adults and Non-responders
|
Phase 1 | |
Terminated |
NCT02604199 -
A Multi-dose Study of ARC-520 in Patients With Hepatitis B 'e' Antigen (HBeAg) Negative, Chronic Hepatitis B Virus (HBV) Infection
|
Phase 2 | |
Completed |
NCT02169674 -
Hepatitis B Booster Study in Adolescence
|
Phase 4 | |
Completed |
NCT02421666 -
A Comparative Trial of Improving Care for Underserved Asian Americans Infected With HBV
|
N/A | |
Completed |
NCT01917357 -
A Comparison of the Immunogenicity and Safety of Quinvaxem in Mono-dose Vials and Uniject
|
Phase 3 | |
Completed |
NCT01732354 -
Study for Consolidation Period of Chronic Hepatitis B
|
||
Completed |
NCT01368497 -
Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic Hepatitis B Virus (HBV) Infection
|
Phase 3 | |
Recruiting |
NCT01462981 -
Cohort of Hepatitis B Research of Amsterdam
|
N/A |