Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB (FINITE CHB)
Withdrawal of antiviral therapy can result in hepatic or alanine aminotransferase (ALT) flares as Hepatitis B Virus (HBV) replication resumes; however, in some patients, a flare exacerbates chronic hepatitis temporarily but can also result in viral clearance. Hepatic flares are common after stopping anti-HBV therapy.
Only patients who already are on treatment with tenofovir disoproxil fumarate (TDF) monotherapy or TDF in combination with lamivudine or emtricitabine for at least 4 years and who achieved and maintained virologic suppression (< 400 copies/mL) for 3.5 or more years will be included in this study. One treatment arm will stop the TDF therapy while the other treatment arm will continue the TDF therapy.
Patients who stop TDF (Arm A) will be monitored very closely with special focus on biochemical flares (especially ALT increases) and virological relapses (Hepatitis B viral load increases). If any subject in the stop therapy arm exceeds one or more predefined limits for such flares or relapses, TDF will be reinstituted.
The study will assess Hepatitis B surface antigen (HBsAg) loss (i.e. specific Hepatitis B virus components are no longer detectable) and seroconversion (occurrence of Hepatitis B surface antibody, a specific antibody which usually occurs after HBsAg loss) rates during study duration. The percentage of patients who need to restart TDF therapy in the stop arm will also be evaluated.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||FINITE CHB - First Investigation in Stopping Tenofovir Disoproxil Fumarate (TDF) Treatment After Long Term Virologic Suppression in HBeAg-negative Chronic Hepatitis B|
- Proportion of participants with HBsAg loss at Week 144 in both study arms [ Time Frame: Week 144 ] [ Designated as safety issue: No ]The proportion of participants with HBsAg loss will be evaluated using the Kaplan-Meier (KM) product limit method. Participants who have not experienced HBsAg loss but discontinue from the study prior to Week 144 are considered censored at the last HBsAg collection date. Log-rank test statistic will be used to compare the time to HBsAg loss between the two treatment arms.
- Proportion of participants with seroconversion in both study arms [ Time Frame: Weeks 96 and 144 ] [ Designated as safety issue: No ]The proportion of participants with seroconversion at Weeks 96 and 144 and will be summarized.
- Change from baseline in quantitative HBsAg (IU/mL) in both study arms [ Time Frame: Baseline to Week 144 ] [ Designated as safety issue: No ]
- Proportion of participants who restart TDF therapy in Arm A [ Time Frame: Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]The proportion of participants who restart TDF therapy in Arm A at Weeks 48, 96 and 144 will be estimated using the Kaplan-Meier (KM) product limit method. Participants who have not re-started TDF therapy but discontinue from the study will be considered as censored at the last laboratory collection date.
- Proportion of participants with viral suppression in Arm A [ Time Frame: Baseline to Week 144 ] [ Designated as safety issue: No ]Viral suppression is defined as not having two consecutive HBV DNA ≥ 400 copies/mL.
- Proportion of participants with ALT < upper limit of the normal range in Arm A [ Time Frame: Baseline to Week 144 ] [ Designated as safety issue: No ]
- Proportion of participants with HBsAg loss at Week 96 in both study arms [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||August 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm A (stop TDF)
Subjects randomized to this arm will stop TDF therapy at baseline
Drug: Stopping TDF therapy
The TDF therapy will be stopped at baseline.
No Intervention: Arm B (continue TDF)
Subjects randomized to this arm will continue their usual TDF therapy
|Berlin, Germany, 10117|
|Berlin, Germany, 13353|
|Leberzentrum am Checkpoint|
|Berlin, Germany, 10969|
|Zentrum für HIV und Hepatitis|
|Duesseldorf, Germany, 40237|
|J.W. Goethe Universitaetsklinikum|
|Frankfurt, Germany, 60590|
|Universitaetsklinikum Hamburg Eppendorf|
|Hamburg, Germany, 20246|
|ifi Studien und Projekte GmbH|
|Hamburg, Germany, 20099|
|Medizinische Hochschule Hannover|
|Hannover, Germany, 30625|
|Heidelberg, Germany, 69120|
|Herne, Germany, 44623|
|Leipzig, Germany, 04103|
|Leverkusen, Germany, 51375|
|Klinikum der LMU Grosshadern|
|Muenchen, Germany, 81377|
|Centrum interdisziplinaere Medizin|
|Muenster, Germany, 48143|
|Tuebingen, Germany, 72076|
|Ulm, Germany, 89081|
|Study Director:||Eduardo Martins, MD||Gilead Sciences|