A Phase 2, Open-Label Randomized Study to Evaluate the Efficacy and Safety of the Combination Product, Emtricitabine/Tenofovir Disoproxil Fumarate in the Presence or Absence of Hepatitis B Immunoglobulin (HBIg) in Preventing Recurrence of Chronic Hepatitis B (CHB) Post-Orthotopic Liver Transplant (OLT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 主要终点
- Percentage of Participants With HBV Recurrence Prior to or at Week 72
研究概览
简要总结
The objective of this 96-week study was to evaluate the safety and antiviral efficacy of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, coformulated; Truvada®) with or without hepatitis B immunoglobulin (HBIg) in preventing the recurrence of chronic hepatitis B following liver transplantation, in participants who were chronically infected with hepatitis B prior to transplantation.
Prior to enrollment, participants were required to have received at least 12 weeks of HBIg therapy following liver transplantation. Enrolled participants then received FTC/TDF plus HBIg for an initial 24-week pre-randomization treatment period. Participants who completed the pre-randomization period and who achieved sustained viral suppression were randomized to continue treatment with FTC/TDF with or without HBIg for an additional 72 weeks (randomized period). The antiviral efficacy of treatment was assessed by measuring hepatitis B virus levels in the blood (HBV DNA). Safety and tolerability was monitored by assessing adverse events and various laboratory parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects (18-75 years of age) with either hepatitis e antigen (HBeAg) positive or HBeAg negative chronic HBV prior to transplant
- •Willing and able to provide written informed consent
- •Subjects with detectable antibody to hepatitis B surface antigen performed by a local laboratory result within 30 days of screening
- •Subjects must have been stable and may not have had 2 or more of the following laboratory parameters associated with decompensated liver disease: conjugated bilirubin > 1.5 x the upper limit of the normal range (ULN), prothrombin time > 1.5 x ULN, platelets < 60,000/mm^3, serum albumin < 3.0 g/dL
- •Must have had at least 12 weeks of center-specific prophylactic therapy including hepatitis B immunoglobulin (HBIg) posttransplant
- •Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation
- •No significant evidence of ongoing deterioration of renal function
- •Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)
排除标准
- •Subjects with HBV recurrence, ie, confirmed HBV DNA ≥ 400 copies/mL, following liver transplant
- •Pregnant women, women who were breast feeding or who believed they may have wished to become pregnant during the course of the study
- •Males and females of reproductive potential who were unwilling to use an effective method of contraception during the study and for at least 30 days from the date of last dose of study drug
- •Evidence of hepatocellular carcinoma (HCC), eg, alpha-fetoprotein > 50 ng/mL, or by any other standard of care measure or presence of multifocal HCC at the time of transplantation if transplantation was within 144 weeks of screening
- •Prior TDF or FTC/TDF experience post-transplant or > 12 months treatment with TDF or FTC/TDF treatment pretransplant
- •Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus pretransplant or at screening
- •Significant renal, cardiovascular, pulmonary, or neurological disease
- •Known hypersensitivity to the study drugs, the metabolites, or formulation excipients
- •Were likely to receive systemic drugs with nephrotoxic potential, except immunosuppressive agents (eg, cyclosporine, tacrolimus), during the course of the study
- •History of variceal bleeding or hepatic encephalopathy following orthotopic liver transplantation
研究组 & 干预措施
FTC/TDF+HBIg
Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF+HBIg in the randomized period.
干预措施: FTC/TDF (Drug)
FTC/TDF+HBIg
Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF+HBIg in the randomized period.
干预措施: Hepatitis B Immunoglobulin (HBIg) (Drug)
FTC/TDF
Participants received FTC/TDF+HBIg for up to 24 weeks in the pre-randomization period; those who completed 24 weeks of treatment were then randomized to receive FTC/TDF in the randomized period.
干预措施: FTC/TDF (Drug)
结局指标
主要结局
Percentage of Participants With HBV Recurrence Prior to or at Week 72
时间窗: Pretreatment baseline through Week 72
HBV recurrence was defined as either HBV DNA ≥ 400 at 2 consecutive visits before Week 72, or HBV DNA ≥ 400 at the Week 72 visit.
次要结局
- Percentage of Participants With HBV Recurrence at Week 96(Week 96)
- Percentage of Subjects With HBV DNA < 169 Copies/mL at Week 72(Week 72)
- Percentage of Participants With HBV DNA < 169 Copies/mL at Week 96(Week 96)
- Percentage of Participants With Normal ALT at Week 72(Week 72)
- Percentage of Participants With Normal ALT at Week 96(Week 96)