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

Chronic Hepatitis B Clinical Trial

— FINITE 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01320943
• Other study ID #: GS-EU-174-0160
• Secondary ID: 2010-021925-12
• Status: Completed
• Phase: Phase 4
• First received: March 9, 2011
• Last updated: August 29, 2016
• Start date: April 2011
• Est. completion date: August 2016

Study information

• Verified date: August 2016
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: August 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

• a-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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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

Other:
• Stop TDF
Participants will stop TDF therapy

Locations

Country	Name	City	State
Germany	Charite CVK	Berlin
Germany	Leberzentrum am Checkpoint	Berlin
Germany	Zentrum für HIV und Hepatitis	Duesseldorf
Germany	J.W. Goethe Universitaetsklinikum	Frankfurt
Germany	ifi Studien und Projekte GmbH	Hamburg
Germany	Universitaetsklinikum Hamburg Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaetsklinik Heidelberg	Heidelberg
Germany	Gastroenterologische Gemeinschaftspraxis	Herne
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Gemeinschaftspraxis Gastroenterologie	Leverkusen
Germany	Klinikum der LMU Grosshadern	Muenchen
Germany	Universitaetsklinikum Ulm	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with HBsAg loss at Week 144 in both study arms	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.	Week 144	No
Secondary	Proportion of participants with seroconversion in both study arms	The proportion of participants with seroconversion at Weeks 96 and 144 and will be summarized.	Weeks 96 and 144	No
Secondary	Change from baseline in quantitative HBsAg (IU/mL) in both study arms		Baseline to Week 144	No
Secondary	Proportion of participants who restart TDF therapy in the Stop TDF arm	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.	Weeks 48, 96, and 144	No
Secondary	Proportion of participants with viral suppression in the Stop TDF arm	Viral suppression is defined as not having two consecutive HBV DNA = 400 copies/mL.	Baseline to Week 144	No
Secondary	Proportion of participants with ALT < upper limit of the normal range in the Stop TDF arm		Baseline to Week 144	No
Secondary	Proportion of participants with HBsAg loss at Week 96 in both study arms		Week 96	No