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

• ClinicalTrials.gov Identifier: NCT01320943
• Recruitment Status: Completed
• First Posted: March 23, 2011
• Results First Posted: August 29, 2017
• Last Update Posted: August 29, 2017
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

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.

Condition or disease	Intervention/treatment	Phase
Chronic Hepatitis B	Drug: TDF; Other: Stop TDF	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Actual Study Start Date: April 26, 2011
• Actual Primary Completion Date: July 28, 2016
• Actual Study Completion Date: August 23, 2016

Arms and Interventions

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 Name: Viread®

Outcome Measures

Primary Outcome Measures :

1. Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms [ Time Frame: Week 144 ]
   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 :

1. Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144 [ Time Frame: 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.
2. Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms [ Time Frame: Baseline to Week 144 ]
   • 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.
3. Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm [ Time Frame: Weeks 48, 96, and 144 ]
4. Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) [ Time Frame: Baseline to Week 144 ]
   Viral suppression is defined as 2 consecutive assessments of HBV DNA < 400 copies/mL (69 IU/mL) through Week 144.
5. 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 ]
6. Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms [ Time Frame: Week 96 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

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: Gilead Study Director; Gilead Sciences

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01320943
• Other Study ID Numbers: GS-EU-174-0160; 2010-021925-12 ( EudraCT Number )
• First Posted: March 23, 2011
• Results First Posted: August 29, 2017
• Last Update Posted: August 29, 2017
• Last Verified: July 2017

• 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

Keywords provided by Gilead Sciences:

stopping oral antiviral therapy; HBsAg loss; seroconversion; restarting oral antiviral therapy

Additional relevant MeSH terms:

Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections