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

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
TDF
Stop TDF
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring stopping oral antiviral therapy, HBsAg loss, seroconversion, restarting oral antiviral therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Leberzentrum am Checkpoint
  • Charite CVK
  • Zentrum für HIV und Hepatitis
  • J.W. Goethe Universitaetsklinikum
  • ifi Studien und Projekte GmbH
  • Universitaetsklinikum Hamburg Eppendorf
  • Medizinische Hochschule Hannover
  • Universitaetsklinik Heidelberg
  • Gastroenterologische Gemeinschaftspraxis
  • Universitaetsklinikum Leipzig
  • Gemeinschaftspraxis Gastroenterologie
  • Klinikum der LMU Grosshadern
  • Universitaetsklinikum Ulm

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Stop TDF

Continue TDF

Arm Description

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

Participants randomized to this arm will continue TDF therapy.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm
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.
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF)
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.

Full Information

First Posted
March 9, 2011
Last Updated
July 27, 2017
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01320943
Brief Title
Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
April 26, 2011 (Actual)
Primary Completion Date
July 28, 2016 (Actual)
Study Completion Date
August 23, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
stopping oral antiviral therapy, HBsAg loss, seroconversion, restarting oral antiviral therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stop TDF
Arm Type
Experimental
Arm Description
Participants randomized to this arm will stop TDF therapy at baseline.
Arm Title
Continue TDF
Arm Type
Active Comparator
Arm Description
Participants randomized to this arm will continue TDF therapy.
Intervention Type
Drug
Intervention Name(s)
TDF
Other Intervention Name(s)
Viread®
Intervention Description
Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily
Intervention Type
Other
Intervention Name(s)
Stop TDF
Intervention Description
Participants will stop TDF therapy
Primary Outcome Measure Information:
Title
Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms
Description
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.
Time Frame
Week 144
Secondary Outcome Measure Information:
Title
Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144
Description
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.
Time Frame
Weeks 96 and 144
Title
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms
Description
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.
Time Frame
Baseline to Week 144
Title
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm
Time Frame
Weeks 48, 96, and 144
Title
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups)
Description
Viral suppression is defined as 2 consecutive assessments of HBV DNA < 400 copies/mL (69 IU/mL) through Week 144.
Time Frame
Baseline to Week 144
Title
Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF)
Time Frame
Baseline to Week 144
Title
Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms
Description
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.
Time Frame
Week 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Leberzentrum am Checkpoint
City
Berlin
ZIP/Postal Code
10969
Country
Germany
Facility Name
Charite CVK
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Zentrum für HIV und Hepatitis
City
Duesseldorf
ZIP/Postal Code
40237
Country
Germany
Facility Name
J.W. Goethe Universitaetsklinikum
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
ifi Studien und Projekte GmbH
City
Hamburg
ZIP/Postal Code
20099
Country
Germany
Facility Name
Universitaetsklinikum Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Universitaetsklinik Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Gastroenterologische Gemeinschaftspraxis
City
Herne
ZIP/Postal Code
44623
Country
Germany
Facility Name
Universitaetsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Gemeinschaftspraxis Gastroenterologie
City
Leverkusen
ZIP/Postal Code
51375
Country
Germany
Facility Name
Klinikum der LMU Grosshadern
City
Muenchen
ZIP/Postal Code
81377
Country
Germany
Facility Name
Universitaetsklinikum Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany

12. IPD Sharing Statement

Citations:
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.
Results Reference
result
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.
Results Reference
result
PubMed Identifier
28736139
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.
Results Reference
derived

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

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