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临床试验/2023-506143-42-00
2023-506143-42-00暂停2 期

A Randomized, Double-Blind Evaluation of the Pharmacokinetics, Safety, and Antiviral Efficacy of Tenofovir Alafenamide (TAF) in Children and Adolescent Subjects with Chronic Hepatitis B Virus Infection

Gilead Sciences Inc.2 个研究点 分布在 1 个国家目标入组 7 人开始时间: 2023年8月24日最近更新:
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试验速览

阶段
2 期
状态
暂停
入组人数
7
试验地点
2
主要终点
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24 [ Time Frame: Week 24 ]
研究概览入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Cohort 1 (adolescents 12 to < 18 years, ≥ 35 kg): -To evaluate the safety, tolerability, and antiviral activity (hepatitis B virus [HBV] DNA < 20 IU/mL) of tenofovir alafenamide (TAF) 25 mg once daily versus placebo at Week 24 in adolescent subjects with chronic hepatitis B (CHB)

Cohort 2 (children 2 to < 12 years of age): Part A:

  • To evaluate the steady-state pharmacokinetics (PK) of TAF and TAF-metabolite, tenofovir (TFV), and confirm the dose of TAF given once daily in children with CHB Part B:
  • To evaluate the safety, efficacy, and tolerability of TAF given once daily at Week 24 in children with CHB
  • To evaluate the antiviral activity (HBV DNA < 20 IU/mL) of TAF given once daily versus placebo at Week 24 in children with CHB

入排标准

年龄范围
0 years 至 17 years（0-17 Years）
接受健康志愿者
是

入选标准

  • •Ages Eligible for Study: 2 Years to 17 Years (Child)
  • •Note: Other protocol defined Inclusion criteria may apply.
  • •Males and non-pregnant, non-lactating females
  • •Weight at screening as follows: Cohort 1 = ≥ 35 kg (≥ 77 lbs) Cohort 2 Group 1 = ≥ 25 kg (≥ 55 lbs) Cohort 2 Group 2 = ≥ 14 kg to < 25 kg (≥ 30 lbs to <55 lbs) Cohort 2 Group 3 = ≥ 10 kg to < 14 kg (≥ 22 lbs to < 30 lbs) or 14 kg to < 25 kg (≥ 30 lbs to < 55 lbs)
  • •Willing and able to provide written informed consent/assent (child and parent/legal guardian)
  • •Documented evidence of CHB (eg, HBsAg-positive for ≥ 6 months)
  • •HBeAg-positive, or HBeAg-negative, chronic HBV infection with all of the following: Screening HBV DNA ≥ 2 × 10^4 IU/mL Screening serum ALT > 45 U/L (> 1.5 × ULN: 30 U/L) and ≤ 10 × ULN (by central laboratory range)
  • •Treatment-naive or treatment-experienced will be eligible for enrollment.
  • •Estimated creatinine clearance (CLCr) ≥ 80 mL/min/1.73m^2 (using the Schwartz formula)

排除标准

  • •Females who are pregnant or breastfeeding
  • •Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the Investigator
  • •Malignancy within the 5 years prior to screening. Individuals under evaluation for possible malignancy are not eligible
  • •Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance.
  • •Note: Other protocol defined Exclusion criteria may apply.'
  • •Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study.
  • •Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
  • •Evidence of hepatocellular carcinoma (Note: if screening alpha-fetoprotein (AFP) is < 50 ng/mL no imaging study is needed; however, if the screening AFP is > 50 ng/mL an imaging study is required)
  • •Any history of, or current evidence of, clinical hepatic decompensation
  • •Abnormal hematological and biochemical parameters
  • •Chronic liver disease of non-HBV etiology (e.g., hemochromatosis, alpha-1 antitrypsin deficiency, cholangitis)
  • •Received solid organ or bone marrow transplant
  • •Currently receiving therapy with immunomodulators (eg, corticosteroids), or immunosuppressants

结局指标

主要结局

Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24 [ Time Frame: Week 24 ]

Incidence of Treatment-Emergent Serious Adverse Events (SAEs) at Week 24 [ Time Frame: Week 24 ]

Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24 [ Time Frame: Week 24 ]

Incidence of Treatment-Emergent Adverse Events (AEs) at Week 24 [ Time Frame: Week 24 ]

Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24 [ Time Frame: Week 24 ]

Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24 [ Time Frame: Week 24 ]

PK Parameter: AUCtau of TAF for participants from Cohort 2 Part A [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 or 12 ]. AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

PK Parameter: AUCtau of TAF for participants from Cohort 2 Part A [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 or 12 ]. AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

次要结局

  • Percentage of participants experiencing graded laboratory abnormalities [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Development as measured by Tanner Stage Assessment [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Percentage change from baseline in bone mineral density (BMD) of whole body (minus head) by dual imaging x-ray absorptiometry (DXA) [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  • Percentage change from baseline in BMD of lumbar spine by DXA [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  • Change from baseline in serum creatinine [ Time Frame: Baseline; Weeks 4, 8, 12, 24, 48, 96, and 240 ]
  • Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  • Incidence of treatment-emergent SAEs in participants treated with TAF or placebo for 24 weeks followed by open-label TAF at Weeks 48, 96 and 240 [ Time Frame: Weeks 48, 96, and 240 ]
  • Incidence of treatment-emergentAEs in participants treated with TAF or placebo for 24 weeks followed by open-label TAF at Weeks 48, 96 and 240 [ Time Frame: Weeks 48, 96, and 240 ]
  • Change from baseline in retinol-binding protein to creatine ratio at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  • Change from baseline in beta-2-microglobulin to creatine ratio at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  • Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  • Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  • Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240 [ Time Frame: Weeks 48, 96, and 240 ]
  • Proportion of participants with plasma HBV DNA < 20 IU/mL (target not detected) at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Composite endpoint of percentage of participants with ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240 [ Time Frame: Weeks 24, 48, 96 and 240 ]
  • Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240 [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  • Percentage of participants with hepatitis B e antigen (HBeAg) loss and seroconversion to anti-HBe (HBeAG-positive participants only) at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Percentage of participants with composite endpoint of HBeAg seroconversion and HBV DNA < 20 IU/mL at Weeks 24, 48, 96, and 240 (in HBeAg-positive participants only) [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Percentage of participants with composite endpoint of ALT normalization, HBeAg seroconversion and HBV DNA < 20 IU/mL at Weeks 24, 48, 96, and 240 (in HBeAg-positive participants only) [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Percentage of participants with hepatitis B surface antigen (HBsAg) loss and seroconversion to anti-HBs at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Percentage of participants with qHBsAg log10 IU/mL at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Incidence of resistance mutations at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  • Acceptability of study drug [ Time Frame: Baseline; Weeks 4, 24, and 36 ] To assess acceptability of study drug, the investigator will ask participants if they were able to taste the medication on a scale of 1-5, how much they like the taste of the medication (1 = dislike very much to 5 = like very much).
  • Palatability of study drug [ Time Frame: Baseline; Weeks 4, 24, and 36 ] To assess palatability of study drug, the investigator will ask participants on a scale of 0-3 how easy it was to swallow the pill (0 = poor to 3 = excellent).
  • PK Parameter: AUCtau of tenofovir (TFV) [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
  • PK Parameter: AUClast of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] AUClast is defined as the concentration of drug from time zero to the last observable concentration.
  • PK Parameter: Ctau of TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] Ctau is defined as the observed drug concentration at the end of the dosing interval.
  • PK Parameter: Cmax of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] Cmax is defined as the maximum observed concentration of drug.
  • .PK Parameter: Clast of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] AUClast is defined as the last observable concentration of drug.
  • PK Parameter: Tmax of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] Tmax is defined as the time of Cmax (the maximum concentration of drug).
  • PK Parameter: Tlast of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] Tlast is defined as the time (observed time point) of Clast.
  • PK Parameter: CL/F of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] CL/F is defined as the apparent oral clearance following administration of the drug.
  • PK Parameter: λz of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
  • PK Parameter: Vz/F of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1),and Week 4, 8, or 12 (Cohort 2) ] Vz/F is defined as the apparent volume of distribution of the drug
  • PK Parameter: t1/2 of TAF and TFV [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 (Cohort 1), and Week 4, 8, or 12 (Cohort 2) ] t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

研究者

申办方类型
Pharmaceutical company
责任方
Principal Investigator
主要研究者

EU CT Support

Scientific

Gilead Sciences Inc.

研究点 (2)

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