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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01320943
First received: March 9, 2011
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

Withdrawal of antiviral therapy can result in hepatic or alanine aminotransferase (ALT) flares as Hepatitis B Virus (HBV) replication resumes; however, in some participants, a flare exacerbates chronic hepatitis temporarily but can also result in viral clearance. Hepatic flares are common after stopping anti-HBV therapy.

Only participants 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.

Participants in the Stop TDF arm will be monitored very closely with special focus on biochemical flares (especially 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 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 participants who need to restart TDF therapy in the Stop TDF arm will also be evaluated.


Condition Intervention Phase
Chronic Hepatitis B
Drug: TDF
Other: Stop TDF
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 the Stop TDF arm [ Time Frame: Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]
    The proportion of participants who restart TDF therapy in Stop TDF arm 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 the Stop TDF arm [ 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 the Stop TDF arm [ 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 ]

Estimated Enrollment: 90
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)
Arms Assigned Interventions
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 Name: Viread®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01320943

Locations
Germany
Leberzentrum am Checkpoint
Berlin, Germany, 10969
Charite CVK
Berlin, Germany, 13353
Zentrum für HIV und Hepatitis
Duesseldorf, Germany, 40237
J.W. Goethe Universitaetsklinikum
Frankfurt, Germany, 60590
ifi Studien und Projekte GmbH
Hamburg, Germany, 20099
Universitaetsklinikum Hamburg Eppendorf
Hamburg, Germany, 20246
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Universitaetsklinik Heidelberg
Heidelberg, Germany, 69120
Gastroenterologische Gemeinschaftspraxis
Herne, Germany, 44623
Universitaetsklinikum Leipzig
Leipzig, Germany, 04103
Gemeinschaftspraxis Gastroenterologie
Leverkusen, Germany, 51375
Klinikum der LMU Grosshadern
Muenchen, Germany, 81377
Universitaetsklinikum Ulm
Ulm, Germany, 89081
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Eduardo Martins, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01320943     History of Changes
Other Study ID Numbers: GS-EU-174-0160, 2010-021925-12
Study First Received: March 9, 2011
Last Updated: May 29, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Gilead Sciences:
stopping oral antiviral therapy
HBsAg loss
seroconversion
restarting oral antiviral therapy

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014