Clinical Pharmacokinetics, Safety and Efficacy Study of Daclatasvir/Sofosbuvir in Adolescents Aged 12 to 18 Years Old With Hepatitis C Virus: A Preliminary Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Measurement of the pharmacokinetics of DCV-SOF
研究概览
简要总结
This is an interventional Phase II/III, single center, single arm clinical trial to assess the pharmacokinetics, efficacy, safety and tolerance of daclatasvir plus sofosbuvir in treatment-naïve, non-cirrhotic adolescents with chronic HCV GT-4 infection.
A single-arm evaluation of daclatasvir/sofosbuvir will focus on the pharmacokinetics, efficacy and safety
All enrolled patients will receive daclatasvir 60 mg orally once daily plus sofosbuvir at a dose of 400 mg orally once daily for 12 weeks.
详细描述
This is an interventional Phase II/III, single center, single arm clinical trial to assess the pharmacokinetics efficacy, safety, and tolerance of daclatasvir plus sofosbuvir in treatment-naïve, non-cirrhotic adolescents with chronic HCV GT-4 infection.
A single-arm evaluation of daclatasvir/sofosbuvir will focus on the efficacy, safety and pharmacokinetics, confirm the favorable pharmacological profile.
All enrolled patients will receive daclatasvir 60 mg orally once daily plus sofosbuvir at a dose of 400 mg orally once daily for 12 weeks.
Patients will be followed closely for disease progression and any hypersensitivity or adverse reactions due to therapy. Laboratory values to be monitored at baseline: Serum creatinine, bilirubin, AST, ALT, HCV viral load (VL).
Fifty patients will be included; the first twenty patients will be candidates for pharmacokinetic assessment. All patients (50), will be candidates for safety and efficacy assessment after verifying the PK results ''phase II''. Patients will be recruited at Ain Shams University hospitals, Egypt. The study will be conducted after approval of the corresponding research ethical committee and obtaining an informed consent from the parents/guardians and an assent from the patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adolescents (ages 12- 18 years) and/ or weight ≥ 35 kg
- •HCV genotype 4 infected
- •Naïve non-cirrhotic population with FIB Score: F0 to F
- •Screening laboratory values within define thresholds
- •Evidence of HCV infection determined by positive anti-HCV antibody and HCV RNA by polymerase chain reaction (PCR)
- •HCV treatment-naïve
- •Absolute neutrophil count ≥ 1,500/mm3
- •Hemoglobin level ≥ 10 g/dL
- •Platelets > 75000 cells/mm3
- •Albumin > 3.5 mg/dL
- •PT < 3 sec above control and INR within accepted range
- •Random glucose level within normal range
- •Serum creatinine < 1.5 mg/dL
- •Biopsy is not required for study entry.
- •Signing informed consent by parents and patient assent
排除标准
- •Previous treatment for HCV.
- •History of clinically significant illness or any other medical condition that may interfere with individuals' treatment, assessment, or compliance with protocol.
- •Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
- •Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage)
- •Pregnant or nursing females
- •Use of any illicit concomitant medications as within 28 days of the Day 1
- •Renal dysfunction
- •Ongoing treatment with Prohibited drugs.
- •Chronic liver disease due to a cause other than HCV e.g. autoimmune disease, Wilson disease,...etc.
- •Alfa-fetoprotein level >50 ng/mL
- •Serum creatinine >1.5 mg/dL
- •Simultaneous acute hepatitis A infection
- •Known hypersensitivity to daclatasvir or sofosbuvir
- •History of gastrointestinal disease or surgical procedure
- •Blood /blood product transfusion within 4 weeks prior to study
- •Systemic corticosteroid use for more than 2 weeks (pulmonary/nasal administration was permitted)
- •Psychiatric hospitalization, suicide attempt or disability resulting from psychiatric illness within the prior 5 years
- •Clinically relevant alcohol or drug abuse within 12 months of screening
- •Ongoing treatment with any medications interacting with daclatasvir/sofosbuvir
研究组 & 干预措施
Daclatasvir and sofosbuvir
Daclatasvir and sofosbuvir
Single arm intervention open label trial for single tablet (Daclatasvir 90 mg and Sofosbuvir 400mg and ) Daclatasvir 90 mg for 12 weeks
干预措施: Daclatasvir and sofosbuvir (Drug)
结局指标
主要结局
Measurement of the pharmacokinetics of DCV-SOF
时间窗: Blood samples will be collected on day 8 of therapy
Blood samples (3 mL) will be collected to measure dactalasvir concentrations from pediatric patients using a nine-point plasma schedule (pre-dose, 0.5,1, 2, 4, 8, 12, and 24 h post-dose) on day 8 of therapy. (This will be a total of 27 mL/patient, which is well below the maximum allowed internationally recognized value of blood loss is 2.4mL/kg in a 4 month period. Any deviations from nominal sampling times should be recorded. AUCtau which is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval will be calculated
次要结局
- Measurement of Number of Participants With sustained virological response (SVR12), 12 weeks after discontinuation of therapy with daclatasvir-sofosbuvir (DCV-SOF).(12 weeks after discontinuation of therapy with daclatasvir-sofosbuvir (DCV-SOF).)
研究者
Manal Hamdy El-Sayed
Professor of Pediatrics
Ain Shams University