A Phase 3 Open-label, Multicenter Study of the Safety, Efficacy, and Pharmacokinetics of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein (rFVIIIFc-VWF-XTEN; BIVV001) in Previously Treated Pediatric Patients <12 Years of Age With Severe Hemophilia A

简要总结

详细描述

主要结局

次要结局

• Annualized Bleeding Rate (ABR): For Treated Bleeds(Baseline up to Week 52)
• Annualized Bleeding Rate for All Bleeding Episodes(Baseline up to Week 52)
• Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)(Baseline up to Week 52)
• Sensitivity Analysis: Annualized Bleeding Rate for All Bleeding Episodes(Baseline up to Week 52)
• Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)(Baseline up to Week 52)
• Sensitivity Analysis: Annualized Bleeding Rate: For Treated Bleeds(Baseline up to Week 52)
• Sensitivity Analysis: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type)(Baseline up to Week 52)
• Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa)(Baseline up to Week 52)
• Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20%(Baseline up to Week 52)
• Number of Injections of BIVV001 Required to Treat a Bleeding Episode(Baseline up to Week 52)
• Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001(Baseline up to Week 52)
• Sensitivity Analysis: Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001(Baseline up to Week 52)
• Change From Baseline in Hemophilia Quality of Life Questionnaire (Haemo-QoL) Kids Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years)(Baseline, Week 52)
• Total Number of Target Joints Resolved in Participants at Week 52(Week 52)
• Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery(During the perioperative period (any time during Baseline up to Week 52))
• Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52(Baseline, Week 52)
• Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years): Parent's Evaluation(Baseline, Week 52)
• Change From Baseline in Hemophilia Quality of Life Questionnaire Kids Short Version Physical Health Domain Score at Week 52 for Children Participants (Aged 8 to <12 Years)(Baseline, Week 52)
• Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery(Day -1 to Day 14)
• Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery(During the perioperative period (any time during Baseline up to Week 52))
• Sensitivity Analysis: Number of Injections of BIVV001 Required to Treat a Bleeding Episode(Baseline up to Week 52)
• Total Dose of BIVV001 Required to Treat a Bleeding Episode(Baseline up to Week 52)
• Sensitivity Analysis: Total Dose of BIVV001 Required to Treat a Bleeding Episode(Baseline up to Week 52)
• Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale(Baseline up to Week 52)
• Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale(Week 13 and Week 52/End of study (EOS)/Early termination (ET))
• Total Annualized BIVV001 Consumption Per Participant(Baseline up to Week 52)
• Annualized Joint Bleeding Rate (AJBR)(Baseline up to Week 52)
• Sensitivity Analysis: Annualized Joint Bleeding Rate (AJBR)(Baseline up to Week 52)
• Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52(Baseline, Week 52)
• Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough)(Pre-dose at Baseline (Day 1) and Week 52)
• Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Physical Health Domain Score at Week 52 for Children Participants (Aged 8 to <12 Years): Parent's Evaluation(Baseline, Week 52)
• Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery(During the perioperative period (any time during Baseline up to Week 52))
• Pharmacokinetics: Volume of Distribution at Steady State (Vss)(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)
• Time Above Predefined (10% and 40%) FVIII Activity Levels(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)
• Pharmacokinetics: Dose-normalized Area Under the Activity-time Curve (DNAUC0-tau)(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)
• Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment(Baseline up to Week 52)
• Pharmacokinetics (PK): Maximum FVIII Activity (Cmax)(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)
• Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery(Day -1 to Day 0 (day of surgery))
• Estimated Blood Loss During Major Surgery(Day 0 (i.e., day of surgery))
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse (TESAEs)(From Baseline (Day 1) up to 3 weeks post last dose of BIVV001 (i.e., up to Week 55))
• Number of Participants With Occurrence of Embolic and Thrombotic Events(Baseline up to Week 52)
• Pharmacokinetics: Elimination Half-life (t1/2z)(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)
• Pharmacokinetics: Mean Residence Time (MRT)(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)
• Pharmacokinetics: Clearance (CL)(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)
• Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau)(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)
• Pharmacokinetics: Total Clearance at Steady State (CLss)(0 hour - 168 hour at week 26, 39 or 52)
• Pharmacokinetics: Incremental Recovery (IR)(Pre-dose, 0.25, 3, 24, 72, and 168 hours post-dose on Day 1)