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

Study Overview
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Brief Summary
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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.

Official Title
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FINITE CHB - First Investigation in Stopping Tenofovir Disoproxil Fumarate (TDF) Treatment After Long Term Virologic Suppression in HBeAg-negative Chronic Hepatitis B

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: TDF
* Other: Stop TDF


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stop TDF<br>Participants randomized to this arm will stop TDF therapy at baseline. | Other: Stop TDF<br>* Participants will stop TDF therapy<br>|
| Active Comparator: Continue TDF<br>Participants randomized to this arm will continue TDF therapy. | Drug: TDF<br>* Tenofovir disoproxil fumarate (TDF) 300 mg tablet administered orally once daily<br>* Other names: Viread®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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) | Viral suppression is defined as 2 consecutive assessments of HBV DNA < 400 copies/mL (69 IU/mL) through Week 144. | 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 | 
| 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. | Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stopping oral antiviral therapy, HBsAg loss, seroconversion, restarting oral antiviral therapy