Phase 4
N=43
Stopping TDF Treatment After Long Term Virologic Suppression in HBeAg-negative CHB
Chronic Hepatitis B
Bottom Line
View on ClinicalTrials.gov: NCT01320943 ↗Enrolled (actual)
43
Serious AEs
16.0%
Results posted
Aug 2017
Primary outcome: Primary: Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms — 0.236; 0 Proportion of participants — p=0.022
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- TDF (Drug); Stop TDF (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- Jul 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms |
0.236; 0 | 0.022 sig |
| SECONDARY Proportion of Participants With HBsAg Seroconversion in Both Study Arms at Weeks 96 and 144 |
0.056; 0; 0.203; 0 | — |
| SECONDARY Change From Baseline in Quantitative HBsAg (IU/mL) in Both Study Arms |
-0.03; NA; -0.03; -0.01; -0.02; NA | — |
| SECONDARY Proportion of Participants Who Restart TDF Therapy in the Stop TDF Arm |
0.143; 0.238; 0.381 | — |
| SECONDARY Percentage of Participants With Viral Suppression in the Stop TDF Arm (TDF-Free and Re-Start TDF Groups) |
52.4; 5.3; 10.0; 5.0; 15.0; 21.1 | — |
| SECONDARY Percentage of Participants With Alanine Aminotransferase (ALT) > Upper Limit of the Normal Range in the Stop TDF Arm (TDF-Free and Restart TDF) |
4.8; 0; 35.0; 60.0; 70.0; 42.1 | — |
| SECONDARY Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms |
0.172; 0 | — |
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.
Eligibility 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) = 70 mL/min by Cockcroft-Gault formula using ideal body weight
- = 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.
Data sourced from ClinicalTrials.gov (NCT01320943). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.