FINITE CHB - First Investigation in Stopping Tenofovir Disoproxil Fumarate (TDF) Treatment After Long Term Virologic Suppression in HBeAg-negative Chronic Hepatitis B
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 13
- 主要终点
- Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Stop TDF
Participants randomized to this arm will stop TDF therapy at baseline.
干预措施: Stop TDF (Other)
Continue TDF
Participants randomized to this arm will continue TDF therapy.
干预措施: TDF (Drug)
结局指标
主要结局
Proportion of Participants With HBsAg Loss at Week 144 in Both Study Arms
时间窗: 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.
次要结局
- 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)
- Proportion of Participants With HBsAg Loss at Week 96 in Both Study Arms(Week 96)
- 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 Seroconversion in Both Study Arms at Weeks 96 and 144(Weeks 96 and 144)