Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB

NCT ID: NCT01320943

Last Updated: 2017-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-26
• Study Completion Date: 2016-08-23

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stop TDF

Participants randomized to this arm will stop TDF therapy at baseline.

Group Type: EXPERIMENTAL

Stop TDF

Intervention Type: OTHER

Participants will stop TDF therapy

Continue TDF

Participants randomized to this arm will continue TDF therapy.

Group Type: ACTIVE_COMPARATOR

TDF

Intervention Type: DRUG

Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily

Interventions

TDF

Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily

Intervention Type: DRUG

Stop TDF

Participants will stop TDF therapy

Intervention Type: OTHER

Other Intervention Names

Viread®

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Leberzentrum am Checkpoint

Berlin, , Germany

Charite CVK

Berlin, , Germany

Zentrum für HIV und Hepatitis

Düsseldorf, , Germany

J.W. Goethe Universitaetsklinikum

Frankfurt, , Germany

ifi Studien und Projekte GmbH

Hamburg, , Germany

Universitaetsklinikum Hamburg Eppendorf

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitaetsklinik Heidelberg

Heidelberg, , Germany

Gastroenterologische Gemeinschaftspraxis

Herne, , Germany

Universitaetsklinikum Leipzig

Leipzig, , Germany

Gemeinschaftspraxis Gastroenterologie

Leverkusen, , Germany

Klinikum der LMU Grosshadern

München, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: DERIVED

PMID: 28736139 (View on PubMed)

Other Identifiers

2010-021925-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-EU-174-0160

Identifier Type: -

Identifier Source: org_study_id