Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Paediatric Patients With Severe Haemophilia A
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Octapharma
- 入组人数
- 11
- 试验地点
- 3
- 主要终点
- Pharmacokinetic (PK) Assessment (Clearance) of FVIII:C
研究概览
简要总结
A prospective, non-controlled, international, multi-centre phase 3 study to investigate the pharmacokinetics, efficacy, safety, and immunogenicity of Wilate in previously treated children with severe haemophilia A
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
- 1 Year 至 11 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Severe haemophilia A (<1% FVIII:C) according to medical history
- •Male patients aged 1 to <12 years
- •Previous treatment with a FVIII concentrate for at least 50 exposure days (EDs)
- •Immunocompetence (CD4+ count >200/μL)
- •Voluntarily given, fully informed written and signed consent obtained by the patient's parent(s) or legal guardian and, depending on the children's developmental stage and intellectual capacity, informed assent by the patients before any study-related procedures are performed
- •The interval between the Screening Visit and the PK Visit should not exceed 30 days. If the 30-day interval is exceeded, determination of the CD4+ count is to be repeated and must be >200/μL for patients to be enrolled (i.e., inclusion criterion no. 4).
排除标准
- •Any coagulation disorders other than haemophilia A
- •History of FVIII inhibitor activity (≥0.6 BU) or detectable FVIII inhibitory antibodies (≥0.6 BU using the Nijmegen modification of the Bethesda assay) at screening, as determined by the central laboratory
- •Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine >120 μmol/L)
- •Patients receiving or scheduled to receive immunomodulating drugs (other than antiretroviral chemotherapy), such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs
研究组 & 干预措施
All patients
All patients will receive Wilate for prophylactic treatment. Patients will also receive Wilate for treatment of breakthrough bleeding events as required
干预措施: Wilate (Drug)
结局指标
主要结局
Pharmacokinetic (PK) Assessment (Clearance) of FVIII:C
时间窗: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate clearance are decilitre (dL)/ hours (h)/ kilograms (kg).
Pharmacokinetic (PK) Assessment (Area Under the Curve (AUC)) of FVIII:C
时间窗: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate AUC is hours (h) x international units (IU)/decilitre (dL).
Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Normalised (AUCNorm)) of FVIII:C for Wilate
时间窗: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The mean area under the curve normalised for the administered dose (AUCnorm) was calculated for Wilate. The units of measure used were AUC divided by dose.
Pharmacokinetic (PK) Assessment (Half-life (h)) of FVIII:C
时间窗: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate half-life is hours.
Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration) for FVIII:C
时间窗: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
PK assessments of FVIII:C were determined using the one-stage (OS) assays. The maximum plasma concentration of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study. Units of measure for maximum plasma concentration are international units (IU)/ decilitre (dL)
Pharmacokinetic (PK) Assessment (Time to Reach Maximum Plasma Concentration (Tmax)) of FVIII:C
时间窗: 48 h following a single dose of Wilate
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate Tmax is hours (h).
Pharmacokinetic (PK) Assessment (Volume of Distribution (Vd)) of FVIII:C
时间窗: 0h, 0.25h, 1h, 6h, 24h and 48 h following a single dose of Wilate
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate Vd is decilitre (dL)/ kilograms (kg).
Pharmacokinetic (PK) Assessment (Mean Residence Time (MRT)) of FVIII:C
时间窗: 48 h following a single dose of Wilate
PK assessments of the factor VIII coagulant activity (FVIII:C) for Wilate were determined using the one-stage (OS) assay. The units of measure to calculate MRT is hours.
Incremental In Vivo Recovery (IVR) of FVIII:C
时间窗: 48 h following a single dose of Wilate
The incremental IVR was determined from all patients at baseline was determined using the one-stage (OS) assay (standardised to 50 IU/kg). The units of measure to calculate IVR is kilograms (kg) / deciliter (dL)
次要结局
- Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)(6 months)
- Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate(6 months)
- Spontaneous Annualized Bleeding Rate (SABR)(6 months)
- Total Annualized Bleeding Rate (TABR)(6 months)
- Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)(6 months)
- Wilate Consumption Data: Average Dose of Wilate Per Week of Study(6 months)
- Safety and Tolerability of Wilate by Monitoring The Number of Adverse Events (AEs) Throughout the Study(6 months)
- Immunogenicity of Wilate: Number of Participants With FVIII Inhibitor Activity at 6 Months(6 months)
- Incremental in Vivo Recovery (IVR) of Wilate Over Time(Baseline, and 3 and 6 months of treatment)
- Virus Safety Measured by the Number With Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study(6 months)