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

FINITE CHB - First Investigation in Stopping Tenofovir Disoproxil Fumarate (TDF) Treatment After Long Term Virologic Suppression in HBeAg-negative Chronic Hepatitis B

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Other: Stop TDF; Drug: TDF

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10969
    • Leberzentrum am Checkpoint
  • Berlin, Germany, 13353
    • Charité CVK
  • Duesseldorf, Germany, 40237
    • Zentrum für HIV und Hepatitis
  • Frankfurt, Germany, 60590
    • J.W. Goethe Universitaetsklinikum
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg Eppendorf
  • Hamburg, Germany, 20099
    • ifi Studien und Projekte GmbH
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Universitaetsklinik Heidelberg
  • Herne, Germany, 44623
    • Gastroenterologische Gemeinschaftspraxis
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig
  • Leverkusen, Germany, 51375
    • Gemeinschaftspraxis Gastroenterologie
  • Muenchen, Germany, 81377
    • Klinikum der LMU Grosshadern
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Stop TDF; Participants randomized to this arm will stop TDF therapy at baseline.	Other: Stop TDF; Participants will stop TDF therapy
ACTIVE_COMPARATOR: Continue TDF; Participants randomized to this arm will continue TDF therapy.	Drug: TDF; Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily; Other Names: Viread®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms	HBsAg loss is defined as qualitative HBsAg result changing from positive at baseline (BL) to negative at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.	Week 144

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144	HBsAg seroconversion is defined as qualitative HBsAb result changing from negative at baseline to positive at any postbaseline visit. Proportions are based on the Kaplan-Meier estimate.	Weeks 96 and 144
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms	The analyses were summarized by 3 treatment subgroups: Stop TDF (TDF-Free), Restart TDF, and Continue TDF; When participant randomized in the Stop TDF group restarted TDF therapy, that participant was considered part of the Restart TDF group from that point forward. For Restart TDF group, baseline is defined as the last available record on or prior to the restart date of TDF.	Baseline to Week 144
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm		Weeks 48, 96, and 144
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups)	Viral suppression is defined as 2 consecutive assessments of HBV DNA < 400 copies/mL (69 IU/mL) through Week 144.	Baseline to Week 144
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF)		Baseline to Week 144
Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms	HBsAg loss is defined as qualitative HBsAg result changing from positive at baseline (BL) to negative at any post-baseline visit. Proportions are based on a Kaplan-Meier estimate.	Week 96

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 26, 2011
• Primary Completion (ACTUAL): July 28, 2016
• Study Completion (ACTUAL): August 23, 2016

Study Registration Dates

• First Submitted: March 9, 2011
• First Submitted That Met QC Criteria: March 21, 2011
• First Posted (ESTIMATE): March 23, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2017
• Last Update Submitted That Met QC Criteria: July 27, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: seroconversion; HBsAg loss; stopping oral antiviral therapy; restarting oral antiviral therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: GS-EU-174-0160; 2010-021925-12 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes