The purpose of this study is to assess efficacy, safety and pharmacokinetics of ADVATE in the treatment and prevention of bleeding episodes (BEs)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
82
* Part 1: Pharmacokinetic (PK) analysis - Subset of 24 participants * Part 2: On-demand treatment regimen * Part 3: Prophylaxis treatment regimen
Peking Union Medical College Hospital
Dongcheng, Beijing Municipality, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
Cangzhou Central Hospital
Cangzhou, Hebei, China
Percentage of reduction in annualized bleed rate (ABR) during prophylactic treatment compared to ABR during on demand treatment
Computed as: {\[median ABR on-demand - median ABR prophylaxis\]÷\[median ABR on-demand\]}\*100% The ABR, will be assumed to have a negative binomial distribution. The 2 treatment regimens (on-demand and prophylaxis) will be compared in terms of mean ABR within a generalized linear model framework (with a logarithmic link function which is the default for the negative binomial distribution), accounting for the fixed effect of study arm and the follow-up time (in years) as an offset. Ratios between treatment means (95% CI) will be estimated within this model.
Time frame: 12 months
Number of units per kg body weight of ADVATE required to resolve a bleeding episode (BE)
Time frame: 12 months
Number of infusions of ADVATE required to resolve a bleeding episode (BE)
Time frame: 12 months
Overall evaluation of efficacy on a four-point scale (Excellent-Good-Fair-Poor)
Time frame: 12 months
Annualized bleeding episode rates (ABR) according to bleed type and bleed etiology summarized by treatment regimen
Bleed types and etiologies summarized by treatment regimen (prophylaxis, on-demand) including: * Joint bleeds * Non-joint bleeds * Spontaneous bleeds * Traumatic bleeds * Target joint bleeds
Time frame: 12 months
Inhibitor incidence
Inhibitor incidence in: 1. Previously treated patients (PTPs) with previous 51-150 exposure days (EDs) to Factor VIII (FVIII) 2. PTPs with previous \>150 EDs to FVIII
Time frame: 13 months
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Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech/ Wuhan Union Hospital
Wuhan, Hubei, China
Tongji Hospital of Tongji Medical College of Hongzhong Science and Techology University
Wuhan, Hubei, China
Xiangya Hospital Central South University
Changsha, Hunan, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
The First Affiliated Hospital of College of Medicine, Zhengjiang University
Hangzhou, Zhejiang, China
Beijing Children's Hospital Affiliated to Capital University of Medical Sciences
Beijing, China
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, China
...and 1 more locations
Adverse events according to relatedness, seriousness, and severity
Time frame: 13 months
Area under the plasma concentration/time curve from time 0 to infinity
Computed as AUC0-t + Ct/ λz, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration, and λz is the terminal rate constant
Time frame: Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Mean Residence Time (MRT)
Computed as AUMC0-∞ / AUC0-∞ - TI/2, where AUMC0-∞ will be determined in a similar manner as AUC0-∞ and TI represents infusion duration \[hour\]
Time frame: Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Clearance (CL)
Computed as Dose/ AUC0-∞
Time frame: Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Incremental Recovery (IR) at Cmax
Computed as: (Cmax - Cpre-infusion)/Dose, where Cmax will be determined as the highest concentration achieved within one hour after infusion
Time frame: Within 30 minutes prior to the start of the infusion, and within 1 hour post-infusion
Elimination phase half-life
Computed as: ln2/ λz. λz will be estimated from the slope of natural log-linear fitting to latter quantifiable concentrations, with largest adjusted R\^2
Time frame: Within 30 minutes prior to the start of the infusion through 48 hours post-infusion
Volume of distribution at steady state (Vss)
Computed as: CL \* MRT
Time frame: Within 30 minutes prior to the start of the infusion through 48 hours post-infusion