Trial record 1 of 1 for:
NCT01320943
Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB (FINITE CHB)
This study is currently recruiting participants.
Verified March 2013 by Gilead Sciences
Sponsor:
Gilead Sciences
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01320943
First received: March 9, 2011
Last updated: March 11, 2013
Last verified: March 2013
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Purpose
Withdrawal of antiviral therapy can result in hepatic or alanine aminotransferase (ALT) flares as Hepatitis B Virus (HBV) replication resumes; however, in some patients, a flare exacerbates chronic hepatitis temporarily but can also result in viral clearance. Hepatic flares are common after stopping anti-HBV therapy.
Only patients 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.
Patients who stop TDF (Arm A) will be monitored very closely with special focus on biochemical flares (especially ALT increases) and virological relapses (Hepatitis B viral load increases). If any subject in the stop therapy 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 patients who need to restart TDF therapy in the stop arm will also be evaluated.
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Hepatitis B |
Drug: Stopping TDF therapy |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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 |
Resource links provided by NLM:
Further study details as provided by Gilead Sciences:
Primary Outcome Measures:
- Proportion of subjects with HBsAg loss at Week 144 in both study arms [ Time Frame: At Week 144 ] [ Designated as safety issue: No ]HBsAg loss will be evaluated by proportion of subjects with HBsAg loss at Week 144 in both Arm A and Arm B using the Kaplan-Meier (KM) product limit method. Subjects 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.
Secondary Outcome Measures:
- Seroconversion [ Time Frame: At Weeks 96 and 144 ] [ Designated as safety issue: No ]The proportion of subjects with seroconversion at Weeks 96 and 144 and will be summarized the same way as for the primary endpoint of proportion of subjects with HBsAg loss at Week 144
- Restarting Therapy [ Time Frame: At Weeks 48, 96 and 144 ] [ Designated as safety issue: No ]The proportion of subjects who restart TDF therapy in Arm A (stop) at Weeks 48, 96 and 144 will be estimated using the Kaplan-Meier (KM) product limit method. Subjects who have not re-started TDF therapy but discontinue from the study will be considered as censored at the last laboratory collection date.
| Estimated Enrollment: | 90 |
| Study Start Date: | March 2011 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | October 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm A (stop TDF)
Subjects randomized to this arm will stop TDF therapy at baseline
|
Drug: Stopping TDF therapy
The TDF therapy will be stopped at baseline.
Other Names:
|
|
No Intervention: Arm B (continue TDF)
Subjects randomized to this arm will continue their usual TDF therapy
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Chronic hepatitis B, hepatitis B e-antigen negative, hepatitis B e-antibody positive, and hepatitis B surface antigen-positive
- 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
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, 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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01320943
Contacts
| Contact: Lothar Gallo, PhD | +49 (0)89 89 98 90 ext 18 | lothar.gallo@gilead.com |
| Contact: Eduardo Martins, MD | +1 (650) 522-5792 | eduardo.martins@gilead.com |
Locations
| Germany | |
| Charite CVK | Recruiting |
| Berlin, Germany, 13353 | |
| Private Practice | Recruiting |
| Berlin, Germany, 10117 | |
| Leberzentrum am Checkpoint | Recruiting |
| Berlin, Germany, 10969 | |
| Universitaetsklinikum Bonn | Recruiting |
| Bonn, Germany, 53105 | |
| Zentrum für HIV und Hepatitis | Recruiting |
| Duesseldorf, Germany, 40237 | |
| J.W. Goethe Universitaetsklinikum | Recruiting |
| Frankfurt, Germany, 60590 | |
| ifi Studien und Projekte GmbH | Recruiting |
| Hamburg, Germany, 20099 | |
| Universitaetsklinikum Hamburg Eppendorf | Recruiting |
| Hamburg, Germany, 20246 | |
| Medizinische Hochschule Hannover | Recruiting |
| Hannover, Germany, 30625 | |
| Universitaetsklinik Heidelberg | Recruiting |
| Heidelberg, Germany, 69120 | |
| Gastroenterologische Gemeinschaftspraxis | Recruiting |
| Herne, Germany, 44623 | |
| Gastroenterologische Gemeinschaftspraxis | Withdrawn |
| Kiel, Germany, 24146 | |
| Universitaetsklinikum Leipzig | Recruiting |
| Leipzig, Germany, 04103 | |
| Gemeinschaftspraxis Gastroenterologie | Recruiting |
| Leverkusen, Germany, 51375 | |
| Universitaetsklinikum Mainz | Withdrawn |
| Mainz, Germany, 55131 | |
| Klinikum der LMU Grosshadern | Recruiting |
| Muenchen, Germany, 81377 | |
| Centrum interdisziplinaere Medizin | Recruiting |
| Muenster, Germany, 48143 | |
| Universitaetsklinik Tuebingen | Recruiting |
| Tuebingen, Germany, 72076 | |
| Universitaetsklinikum Ulm | Recruiting |
| Ulm, Germany, 89081 | |
Sponsors and Collaborators
Gilead Sciences
Investigators
| Study Director: | Eduardo Martins, MD | Gilead Sciences |
More Information
No publications provided
| Responsible Party: | Gilead Sciences |
| ClinicalTrials.gov Identifier: | NCT01320943 History of Changes |
| Other Study ID Numbers: | GS-EU-174-0160, 2010-021925-12 |
| Study First Received: | March 9, 2011 |
| Last Updated: | March 11, 2013 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Gilead Sciences:
|
stopping oral antiviral therapy HBsAg loss seroconversion restarting oral antiviral therapy |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis B Hepatitis, Chronic Hepatitis B, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections DNA Virus Infections Tin Fluorides |
Tenofovir Tenofovir disoproxil Cariostatic Agents Protective Agents Physiological Effects of Drugs Pharmacologic Actions Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Anti-HIV Agents |
ClinicalTrials.gov processed this record on May 23, 2013