Chronic Hepatitis BPhase 4FINITE CHBNCT01320943
Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB
A Phase 4 study testing TDF and Stop TDF in people with Chronic Hepatitis B, run by Gilead Sciences at 13 sites in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- TDF and Stop TDF
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 13 sitesGermany
- Study dates
- 26 Apr 2011to 23 Aug 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Germany13 sites
Leberzentrum am Checkpoint
Berlin, 10969
Charite CVK
Berlin, 13353
Zentrum für HIV und Hepatitis
Düsseldorf, 40237
J.W. Goethe Universitaetsklinikum
Frankfurt, 60590
ifi Studien und Projekte GmbH
Hamburg, 20099
Universitaetsklinikum Hamburg Eppendorf
Hamburg, 20246
Medizinische Hochschule Hannover
Hanover, 30625
Universitaetsklinik Heidelberg
Heidelberg, 69120
Gastroenterologische Gemeinschaftspraxis
Herne, 44623
Universitaetsklinikum Leipzig
Leipzig, 04103
Gemeinschaftspraxis Gastroenterologie
Leverkusen, 51375
Klinikum der LMU Grosshadern
München, 81377
Universitaetsklinikum Ulm
Ulm, 89081
About this study
Official title: FINITE CHB - First Investigation in Stopping Tenofovir Disoproxil Fumarate (TDF) Treatment After Long Term Virologic Suppression in HBeAg-negative Chronic Hepatitis B
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
- Being tested
- TDF, Stop TDF
- Keywords
- stopping oral antiviral therapy, HBsAg loss, seroconversion, restarting oral antiviral therapy
- Medical subject headings
- Hepatitis B, Chronic, HIV Seropositivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDFDrug
Also called Viread®
Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily
Stop TDFOther
Participants will stop TDF therapy
| Study group | Role | What they receive |
|---|---|---|
| Stop TDF | Experimental | Participants randomized to this arm will stop TDF therapy at baseline. Receives: Other: Stop TDF |
| Continue TDF | Active comparator | Participants randomized to this arm will continue TDF therapy. Receives: Drug: TDF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 144
Secondary outcomes (6)
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.
Measured: Weeks 96 and 144
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.
Measured: Baseline to Week 144
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm
Measured: Weeks 48, 96, and 144
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.
Measured: 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)
Measured: Baseline to Week 144
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.
Measured: Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2011 (estimated)
- Study start26 Apr 2011
- Primary completion28 Jul 2016
- Study completion23 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01320943
- Sponsor's protocol ID
- GS-EU-174-0160
- Other IDs
- 2010-021925-12
- Acronym
- FINITE CHB
- Status last verified
- Jul 2017
- First submitted
- 9 Mar 2011
- Last updated
- 29 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
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.
PubMed 28736139
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FINITE CHB - First Investigation in Stopping Tenofovir Disoproxil Fumarate (TDF) Treatment After Long Term Virologic Suppression in HBeAg-negative Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT01320943
- Acronym / sponsor ID
- FINITE CHB / GS-EU-174-0160
- Conditions
- Chronic Hepatitis B
- Keywords
- stopping oral antiviral therapy, HBsAg loss, seroconversion, restarting oral antiviral therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 26 Apr 2011 (actual)
- Primary completion
- 28 Jul 2016 (actual)
- Study completion
- 23 Aug 2016 (actual)
- First posted
- 23 Mar 2011 (estimated)
- Results
- Posted 29 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stop TDF | Experimental | Other: Stop TDFParticipants randomized to this arm will stop TDF therapy at baseline. |
| Continue TDF | Active comparator | Drug: TDFParticipants randomized to this arm will continue TDF therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TDFAlso: Viread®Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily | Drug | Continue TDF |
| Stop TDFParticipants will stop TDF therapy | Other | Stop TDF |
Primary outcome
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.
6 secondary outcomes
Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144
Time frame: Weeks 96 and 144
Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms
Time frame: Baseline to Week 144
Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm
Time frame: Weeks 48, 96, and 144
Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups)
Time frame: 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)
Time frame: Baseline to Week 144
Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms
Time frame: Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationBerg 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 publicationBerg 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.
- Derived from this study: PubMed 28736139Berg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TDF and Stop TDF in people with Chronic Hepatitis B, run by Gilead Sciences at 13 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms (time frame: Week 144). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01320943, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2017.