Comparison of Outcomes Between Low Dose Emicizumab and Extended Half-life Factor VIII With Pharmacokinetic-guided Prophylaxis in Clinically Severe Hemophilia A
Phase: PHASE2
Conditions: Severe Hemophilia A Without Inhibitor, Joint Bleed
Sponsor: Chulalongkorn University

Version 3 Date 24 November 2023 
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Study Protocol 
 
Title 
Comparison of outcomes between low dose Emicizumab and low dose 
factor VIII prophylaxis in clinically severe hemophilia A 
 
Principal Investigator 
 
 
Nuchanun Kessakorn, MD 
The Pediatric Hematology-Oncology Fellowship Program at King 
Chulalongkorn Memorial Hospital 
Co-investigators  
 
 
Prof.Dr. Darintr Sosothikul, Diplomat 
 Professor at Pediatric Hematology-Oncology, King Chulalongkorn  
Memorial Hospital 
 
Study centers & Address 
 
Pediatric Hematology-Oncology Unit, King Chulalongkorn  
Memorial Hospital 
 
Study period  
 
 
12 months 
 
Objectives: 
- Primary objective: To compare outcome between Extended half-life FVIII concentrates with pharmacokinetic 
guided and low dose Emicizumab using Annualized bleeding rate, Annualized joint bleeding rate, and HemoQol in 
patient with clinically severe Hemophilia A 
- Secondary objective: To study about pharmacokinetic and side effect of emicizumab 
 
Study design: Interventional study without concurrent controls: Before-after (pre-post) studies 
 
Population and Sample size 
- Target population: patient with clinically severe Hemophilia A follow up in Pediatric Hematology-Oncology Unit, 
King Chulalongkorn Memorial Hospital 
- Sample size: 15 
 
Informed Consent Process Investigator give all patients about study information then contact back to investigator 
if one was interested to participate in the study then sign consent before enrolled and appoint for next visit 
 
Study procedure 
- Interventional study without concurrent controls: Before-after (pre-post) studies 

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- Pre-intervention defined as using low dose factor VIII prophylaxis. And Post-intervention defined as  using low 
dose emicizumab (2 mg/kg/dose) Then compare Annualized bleeding rate (ABR), Annualized joint bleeding rate, 
AJBR, Quility of life (HemoQoL) before and after prophylaxis bleeding with low dose Emicizumab. First month, 
loading emicizumab 1-1.5 mg/kg/dose subcutaneous every 2 weeks then maintenance with same dose every 4 
weeks for 6 months 
 
Comparator, dosage & mode of administration 
- Extended half-life FVIII concentrates intravenous using PK-based for at least 6 months 
 
Duration of participation for each volunteer – at least 6 months 
 
Outcome variables 
- Primary: New choice of Prophylactic treatment for clinically severe Hemophilia A 
- Secondary: Improve Annualized bleeding rate (ABR), Annualized joint bleeding rate (AJBR), and quality of life for 
clinically severe Hemophilia A 
 
Statistical method 
- Median and interquartile range (percentile 25-75) for continuous variables 
- Frequency and percentage for discrete variables 
- Wilcoxon Signed rank test: to compare outcome between before-after low dose emicizumab 
- Pearson’s correlation coefficiency: to find correlation factor affect emicizumab levels 
- Paired t test : to compare ABR, AJBR between before-after low dose emicizumab 
- P<0.05 is statistic significant 
 
Ethical Consideration: Respect of person, Beneficence/Non-malefience, and Justice: Study protocol have been 
approved by Institutional review board, Faculty of medicine, Chulalongkorn University 
 
 
Approved by Institutional review board COA No 08-0/2023 
 
 
 
 
       IRB No. 0206/66