Clinical trial NCT01320943: Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB
Official title: FINITE CHB - First Investigation in Stopping Tenofovir Disoproxil Fumarate (TDF) Treatment After Long Term Virologic Suppression in HBeAg-negative Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: stopping oral antiviral therapy
HBsAg loss
seroconversion
restarting oral antiviral therapy
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-03-23
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate hepatitis B surface antigen (HBsAg) loss and seroconversion in participants who stop tenofovir disoproxil fumarate (TDF) (Stop TDF arm) compared to participants who continue TDF (Continue TDF arm).

Only participants who already are on treatment with 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. Participants in the Stop TDF arm will be monitored very closely with special focus on biochemical flares (especially alanine aminotransferase (ALT) increases) and virological relapses (Hepatitis B viral load increases). If any participant in the Stop TDF arm exceeds one or more predefined limits for such flares or relapses, TDF treatment will be reinstituted.


Eligibility criteria: Key Inclusion Criteria:

* Chronic hepatitis B, hepatitis B e-antigen negative, hepatitis B e-antibody positive, and hepatitis B surface antigen-positive
* Hepatitis B e Antigen (HBeAg)-negative at the beginning of TDF therapy (i.e. TDF monotherapy or combination of TDF + lamivudine or TDF + emtricitabine)
* Received continuous TDF therapy (i.e. TDF monotherapy or combination of TDF + lamivudine or TDF + emtricitabine) treatment for at least 4 years prior to screening. If TDF has been used in combination with lamivudine or emtricitabine, lamivudine or emtricitabine must have been stopped at least 12 weeks prior to screening
* Documented hepatitis B virus DNA (HBV DNA) \< 400 copies/mL for at least 3.5 years prior to screening and at screening
* ALT within normal range
* α-fetoprotein (AFP) \<= 50 ng/mL
* Calculated creatinine clearance \>= 70 mL/min by Cockcroft-Gault formula using ideal body weight
* \<= 10 kPa on Fibroscan assessment
* A negative serum pregnancy test for female subjects
* Adult subjects \>= 18 years of age

Key Exclusion Criteria:

* Known cirrhosis
* Evidence of fibrosis \>= Stage 3 (METAVIR) on liver biopsy or Fibroscan \> 10 kPa within 6 months prior to screening
* Documentation of confirmed episodes (i.e., 2 consecutive values) of HBV DNA \> 400 copies/mL within 3.5 years prior to screening
* History of decompensated liver disease (defined as direct \[conjugated\] bilirubin \> 1.5 x upper limit of normal, prothrombin time (PT) \> 1.5 x upper limit of normal, platelets \< 75,000/mm³, serum albumin \< 3.0 g/dL
* History of clinical hepatic decompensation in the judgement of the investigator
* Evidence of hepatocellular carcinoma
* Significant bone disease (in the judgment of the investigator)
* Serological evidence of coinfection with human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis D infection
* Known hypersensitivity to TDF, its metabolites, or formulation excipients
* Concomitant therapy with disallowed medications
* History of malignant disease
* Lactating females
* Females wishing to became pregnant during the duration of the stud
* Subjects participating in another clinical trial can only be enrolled at the discretion of the Medical Monitor

Note: Other protocol defined inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms
timeFrame: Week 144
Secondary outcomes:
measure: Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144
timeFrame: Weeks 96 and 144
measure: Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms
timeFrame: Baseline to Week 144
measure: Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm
timeFrame: Weeks 48, 96, and 144
measure: Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups)
timeFrame: Baseline to Week 144
measure: Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF)
timeFrame: Baseline to Week 144
measure: Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms
timeFrame: Week 96
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Leberzentrum am Checkpoint
city: Berlin
country: Germany
facility: Charite CVK
city: Duesseldorf
country: Germany
facility: Zentrum für HIV und Hepatitis
city: Frankfurt
country: Germany
facility: J.W. Goethe Universitaetsklinikum
city: Hamburg
country: Germany
facility: ifi Studien und Projekte GmbH
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitaetsklinik Heidelberg
city: Herne
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Leverkusen
country: Germany
facility: Gemeinschaftspraxis Gastroenterologie
city: Muenchen
country: Germany
facility: Klinikum der LMU Grosshadern
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Berg T, Schott E, Felten G, Eisenbach C, Welzel TM, Warger T, et al. Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-Negative CHB: Two Cases From an Ongoing Randomized, Controlled Trial [Poster Number P47] The Viral Hepatitis Congress; 2012 September 7-9; Frankfurt am Main, Germany.
citation: Berg T, Simon K-G, Mauss S, Schott E, Heyne R, Klass D, et al. Stopping Tenofovir Disoproxil Fumarate Treatment After Long-Term Virologic Suppression in HBeAg-Negative CHB: Week 48 Interim Results From an Ongoing Randomized, Controlled Trial ("FINITE CHB") [Presentation P119]. The European Association for the Study of the Liver (EASL). 50th International Liver Congress; 2015 22-26 April; Vienna, Austria.
citation: Berg T, Simon KG, Mauss S, Schott E, Heyne R, Klass DM, Eisenbach C, Welzel TM, Zachoval R, Felten G, Schulze-Zur-Wiesch J, Cornberg M, Op den Brouw ML, Jump B, Reiser H, Gallo L, Warger T, Petersen J; FINITE CHB study investigators [First investigation in stopping TDF treatment after long-term virological suppression in HBeAg-negative chronic hepatitis B]. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study. J Hepatol. 2017 Nov;67(5):918-924. doi: 10.1016/j.jhep.2017.07.012. Epub 2017 Jul 21.