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

NCT01320943 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: GS-EU-174-01602010-021925-12
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 13

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.

Conditions

Chronic Hepatitis B

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144

  Weeks 96 and 144

• Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms

  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)

  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

Study Arms (2)

Stop TDF

EXPERIMENTAL

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

Other: Stop TDF

Continue TDF

ACTIVE COMPARATOR

Participants randomized to this arm will continue TDF therapy.

Drug: TDF

Interventions

TDF DRUG

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

Also known as: Viread®

Continue TDF

Stop TDF OTHER

Participants will stop TDF therapy

Stop TDF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (13)

Leberzentrum am Checkpoint

Berlin, 10969, Germany

Location

Charite CVK

Berlin, 13353, Germany

Location

Zentrum für HIV und Hepatitis

Düsseldorf, 40237, Germany

Location

J.W. Goethe Universitaetsklinikum

Frankfurt, 60590, Germany

Location

ifi Studien und Projekte GmbH

Hamburg, 20099, Germany

Location

Universitaetsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitaetsklinik Heidelberg

Heidelberg, 69120, Germany

Location

Gastroenterologische Gemeinschaftspraxis

Herne, 44623, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Gemeinschaftspraxis Gastroenterologie

Leverkusen, 51375, Germany

Location

Klinikum der LMU Grosshadern

München, 81377, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

Related Publications (3)

• 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.

  RESULT

• 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.

  RESULT

• 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.

  PMID: 28736139 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic; HIV Seropositivity

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; HIV Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2011
• First Posted: March 23, 2011
• Study Start: April 26, 2011
• Primary Completion: July 28, 2016
• Study Completion: August 23, 2016
• Last Updated: August 29, 2017
• Results First Posted: August 29, 2017

Record last verified: 2017-07

Locations

DE (13)