Comparison of Low Dose Emicizumab and Low Dose Factor VIII as a Prophylaxis in Hemophilia A Patients- a Randomized Control Trial'
Phase: PHASE2
Conditions: Hemophilia A
Sponsor: Dhaka Medical College

 
PROTOCOL TITLE 
Comparison of Low Dose Emicizumab and Low Dose Factor VIII as 
a Prophylaxis in Hemophilia A patients- A Randomized Control 
Trail.  
 
Place of Study 
: 
Department of Hematology and BMT Unit, 
Dhaka Medical College Hospital 
Dhaka-1000, Bangladesh.  
 
Organization's Unique 
Protocol ID 
 
: 
ERC-DMC/ECC/2024/215 
Type of the study 
: 
Experimental Study- Randomized Control 
Trial  
 
Duration of study 
: 
One year  
 
 
Expected time of start   
: 
01.04.2025 
 
 
Last Update of the 
protocol submitted  
 
 
: 
01.02.2025 
 
 
 

Introduction 
Haemophilia A is an X-linked bleeding disorder that arises from mutation in factor VIII gene 
resulting in under production or dysfunction of coagulation factor VIII (FVIII). It affects one in 
5000 live male births (CDC 2018). Patients with plasma factor VIII level <0.01IU/ml are 
classified as having severe Haemophilia A, those with level 0.01-0.05 IU/ml as moderate 
Haemophilia A and those with level >0.05-0.40 IU/ml as mild Haemophilia A [1]. 
 
Patients with severe hemophilia experience frequent spontaneous bleeding events, eighty percent 
of which occur in the musculo-skeletal system, while twenty percent take place in the central 
nervous system and other organ systems such as skin, GIT and other mucous membrane [2]. 
Recurrent joint bleeding is a hallmark of severe hemophilia A and a major cause of morbidity, 
leading to progressive irreversible joint damage and the development of hemophilic arthropathy 
[3].  
 
Haemophilic bleeding events are treated with recombinant FVIII concentrate. But such episodic 
factor replacement therapy does not alter the natural history of spontaneous bleed leading to 
musculoskeletal damage and other complications due to bleeding. Therefore, Prophylaxis is 
recommended by the World Federation of Hemophilia as the standard of care for patients with 
severe hemophilia or with severe clinical phenotype, especially in young children [4]. Regular 
prophylaxis among patients with severe haemophilia A has clear efficacy to prevent bleeding 
episodes and subsequent sequelae of muscles and joints damage.  
 
Regular prophylaxis with intravenous FVIII concentrates is considered as the standard of care in 
many countries especially developed countries. Factor VIII prophylaxis is 3 types- high dose 
prophylaxis (25-40 IU/kg 3 times/week), intermediate dose prophylaxis (15-25 IU/kg 3 
times/week), and low dose prophylaxis (10-15 IU/kg 2- 3 times/week). Low dose prophylaxis 
approach has been adopted as an economically feasible alternative to high dose prophylaxis in 
resource-constrained countries because it resulted in improved outcomes compared to on-
demand treatment in terms of ABR, joint bleeding and hospitalization [5].  
 

Owing to the short half-life of about 12 hours, at least two intravenous infusions per week is 
required that may be burdensome for paediatric patients and their caregivers and may necessitate 
the use of central venous access with the risk of infection-related complications [6]. In addition, 
20%–30% of patients develop inhibitors requiring immune tolerance induction (ITI) with a 
reported success rate of∼53% to 79% [7,8]. For patients undergoing or refractory to immune 
tolerance induction therapy, bleeding events are controlled with bypassing agents (e.g, 
recombinant activated FVII [rFVIIa] or activated prothrombin complex concentrate [aPCC]). 
Although these treatments can be efficacious for many patients, neither of these therapies is 
considered as effective as FVIII replacement and there is no reliable laboratory measure of their 
hemostatic effect [9]. So, there is a need for alternative non-factor agent. 
 
Emicizumab (Hemlibra®, Roche), which is a humanized, bispecific, monoclonal antibody, as 
one non-factor product, could bridge activated factor IX and factor X, replacing the function of 
FVIII and restoring hemostasis in HA patients [10].  Considering its high bioavailability and 
long half-life time of about 30 days, emicizumab has the potential to improve patient adherence 
largely, which attributes to its long interval and subcutaneous injection. As reported by previous 
well-designed clinical trials, emicizumab has a strong capacity to reduce bleeds compared with 
traditional prophylaxis using FVIII concentrates [11,12,13,14]. Owing to a complete absence of 
structure homology compared to FVIII, emicizumab is not suspected to induce FVIII inhibitor 
and can play it’s role irrespective of presence of FVIII inhibitor [15]. Long-term emicizumab 
prophylaxis demonstrated a favorable safety profile with encouraging efficacy. However, the 
standard regimen, consisting of four weekly loading doses of 3 mg/kg followed by a 
maintenance dose at 1.5 mg/kg weekly or 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks, is 
costly and unaffordable for economically constrained countries limiting patient access. Any 
treatment protocol using a lower dose with almost equivalent efficacy will have significant 
impact on access to prophylaxis and the overall quality of life (QoL) of PwHA in low-or middle-
income countries [16]. Low dose monthly Emicizumab with or without initial four loading doses 
has been found effective in reducing annualized bleeding rate significantly in few recent studies 
[17].  
 
 

 
Rationale of the study 
Low dose factor VIII prophylaxis is practiced around the world. Role of standard dose 
Emicizumab prophylaxis is well established. Emicizumab is an expensive drug. Standard dose 
Emicizumab prophylaxis is very expensive for hemophilia A patients and troublesome for 
government to ensure continuous supply. We intend to compare low dose Factor VIII 
prophylaxis with low dose Emicizumab prophylaxis and compare whether low dose Emicizumab 
is as effective as low dose Factor VIII prophylaxis. So, we can continue prophylaxis program in 
hemophilia A patients with a cost-effective way in our country without risking the patient health.  
Moreover, Emicizumab prophylaxis reduces the chance of developing inhibitor to Factor VIII.   
 
 
 

Hypothesis 
Low dose Emicizumab prophylaxis is as effective as low dose Factor VIII prophylaxis in 
hemophilia A patients.   
 
 
 
 
 

Research objectives 
General objective 
• To determine whether low dose Emicizumab prophylaxis is as effective as low dose 
Factor VIII prophylaxis in hemophilia A patient.   
Specific objectives 
• To assess effect of low dose Emicizumab prophylaxis in hemophilia A patient by means 
of determining annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), 
annualized spontaneous bleeding rate (ASBR), APTT.  
• To assess effect of low dose Factor VIII prophylaxis in hemophilia A patient by means of 
determining annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), 
annualized spontaneous bleeding rate (ASBR), APTT.  
• To compare the variables among low dose Emicizumab prophylaxis and low dose Factor 
VIII prophylaxis group.  
 
 
 

Materials and Methods 
Study design: Experimental study- Randomized Control Trial.  
Study period: One year (July 2024 to June 2025) 
 
Place of study: Department of Hematology and Bone Marrow Transplant Unit, Dhaka Medical 
College Hospital (DMCH), Dhaka, Bangladesh. 
Study population: Severe hemophilia A patients attending in department of Hematology and 
Bone Marrow Transplant Unit, Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh. 
Selection criteria 
Inclusion criteria: 
Low dose Emicizumab group (Case group) 
1. Severe hemophilia A patient with or without inhibitor to factor VIII.  
Low dose Factor VIII group (Control group) 
1. Severe hemophilia A patient without inhibitor to factor VIII. 
Exclusion criteria: 
Low dose Factor VIII group (Control group) 
1. Severe hemophilia A patient with inhibitor to factor VIII.  
Sample Size: Sample size is determined by availability of drugs rather than any scientific 
formula. We can provide Emicizumab to 10 patients for 28 weeks as prophylaxis. So, we intend 
to include 10 patients in each group. [18] 
 

Sampling technique: Block Randomization. Severe hemophilia A patients will be randomized 
6:4:10 in patients with inhibitor (Emicizumab Group): Patients without inhibitor (Emicizumab 
Group): Patients without inhibitor (Factor VIII Group). Randomization will be generated by 
computer. One such plan has been added in appendix.  
Variables  
A. Independent variable 
1. Socio-demographic variables 
• Age 
• Educational status 
• Weight  
• Occupation  
2. Variables related to Hemophilia 
• Severity of hemophilia A – Moderate or Severe 
• Presence of Inhibitor  
B. Dependent variable 
1. Main outcome variables-  
• Annualized bleeding rate (ABR) 
• Annualized joint bleeding rate (AJBR) 
• Annualized spontaneous bleeding rate (ASBR) 
• APTT 
2. Confounding variables-  
• Development of new inhibitor to factor VIII 

 
Study procedure 
 
This study will be conducted in the department of Hematology and Bone Marrow Transplant 
Unit, Dhaka Medical College Hospital (DMCH), Dhaka for one year duration following approval 
from the Institutional review board (IRB), DMCH. 
we will select 20 severe hemophilia A patients randomly from interested patients. we will 
randomize 6 patients with inhibitor to factor VIII in Low dose Emicizumab with Inhibitor group 
(I) and rest 14 will be randomized by block randomization in Low dose Emicizumab (without 
inhibitor-WI) and low dose Factor VIII group at 4:10 ratio. Patients and/or parents will be 
thoroughly informed about the study, drugs to be used, risk & benefits and follow up plan. Their 
consent for this study will be taken and they will be enrolled in the study. For Participants under 
18 years, consent will be obtained from parents or legal guardian. Participants ≥18 years will 
give his/her own consent. 
Randomization will be generated by computer. One such plan has been added in the end of 
protocol. 
Dose- Emicizumab 0.8-1.5mg/kg weekly for 4 weeks as loading dose. Then 0.8-1.5mg/kg 4 
weekly for 24 weeks. Inj. Emicizumab has 30mg in vail. Dose will be round up to 30mg, 60 mg 
or any dose nearest to 1 mg/kg when fractionation of vail is possible.  
Factor VIII- 10-15 unit/Kg twice/thrice weekly for 28 weeks. Inj. Factor VIII is available in 
250U, 500U, 750U vails. Dose will be round up to full nearest full vail strength.  
If extended half-life injection is available- twice weekly. If standard half-life Factor VIII is 
available- thrice weekly.  

 
Follow Up-  
Participants in Emicizumab group will visit weekly for first 4 week than once 4 weekly for 24 
weeks (Total 28 weeks). 
Participants in Factor VIII group will visit twice/thrice weekly for 28 weeks. Information of data 
collection sheet will be collected once in a week.  
Patient has to come physically for every dose schedule. He will be asked for number of bleeding- 
traumatic, spontaneous bleeding, joint bleeding, frequency of hospital visit due to hemophilia 
related problems in between doses and investigate for APTT.  
Participants in Emicizumab group will visit weekly for first 4 week than once 4 weekly for 24 
weeks.  
Participants in Factor VIII group will visit twice/thrice weekly for 28 weeks. Information of data 
collection sheet will be collected once in a week.  
Primary End Point- This study will include 28 weeks follow up of the patients. Each patient 
will receive 28 weeks prophylaxis. After that patients will continue prophylaxis if drugs are 
available but would not be included in the study. Otherwise, they will receive on demand 
treatment in our HTC (hemophilia treatment center). Patient would continue therapy and follow 
up in OPD but would not be included in the study. 
Supportive care and rescue-  

A Data and Safety Monitoring Board (DSMB) will be formed which will include members 
suggested by IRB. Any adverse event or serious adverse event (will be delt with proper medical 
care.  
If any patient developed spontaneous or traumatic bleeding episode during prophylaxis, they will 
be treated with standard dose on demand treatment on priority basis.  
Pharmacodynamics and pharmacokinetics of Emicizumab and Factor VIII 
Pharmacodynamics and pharmacokinetics of Emicizumab and Factor VIII is attached in 
appendix III 
Data Collection-  
Data will be collected on predesigned case record form and will be collected by face-to-face 
interview, physical examination and collecting laboratory reports.  
Data Analysis 
After data collection data will be edited, cleaned and prepared for analysis at the end of the 
study. The statistical analysis will be conducted using SPSS (statistical package for the social 
science) version 25 statistical software.  The findings of the study will be presented by frequency 
and percentage in tables. Main outcome variables- Annualized bleeding rate (ABR), Annualized 
joint bleeding rate (AJBR), Annualized spontaneous bleeding rate (ASBR), APTT will be 
compared (mean) among the groups by Anova/ Kruskal Wallis test (considering distribution of 
data). Where p<0.05 with 95% confidence level will be considered as significant.  
 

 
 
Operational definitions 
Severity of hemophilia-  
Severe- Factor VIII level <1 IU/dL (<0.01 IU/mL) or <1% of normal  
Moderate- Factor VIII level 1- 5 IU/dL (0.01- 0.05 IU/mL) or 1- 5% of normal 
Mild- Factor VIII level 5- 40 IU/dL (0.05- 0.40 IU/mL) or 5- <40% of normal 
 
Annualized bleeding rate (ABR)- ABR will be calculated as the number of reported bleeding 
events divided by the number of months in the reporting time window (8 weeks to 12 months) 
and multiplied by 12. [19] 
Annualized joint bleeding rate (AJBR)- AJBR will be calculated as the number of reported 
joint bleeding events divided by the number of months in the reporting time window (8 weeks to 
12 months) and multiplied by 12. [19] 
Annualized spontaneous bleeding rate (ASBR)- ASBR will be calculated as the number of 
reported spontaneous bleeding events divided by the number of months in the reporting time 
window (8 weeks to 12 months) and multiplied by 12. [19] 
 
 

Ethical consideration 
• Before starting this study, the research protocol will be submitted and approved by the 
Institutional Review Board of DMCH, Dhaka.  
• We are not exposing patient to any new drugs which safety and efficacy is not well 
established. Both Emicizumab and factor VIII injections are widely used among 
hemophilia patients.  
• All participants will be informed about the objectives, methodology and purpose of the 
study in an easily understandable way.  
• All information regarding benefits and hazards regarding the study will be delivered to 
the all participants & only those who agree to participate will be included in the study.  
• Verbal and written consents will be obtained from all participants without any influences 
prior to data collection.  
• Data obtained from the study will be used only for research purposes. The confidentiality 
of all study information will be maintained strictly.  
• Participants can withdraw themselves from the study at any time even after giving 
consent.  
 
 
 
 
 

Methods of maintaining confidentiality 
• Research data will be coded. 
• Data will be stored in a locked cabinet. 
• Only research personnel will be allowed to access data. 
• There is minimum physical, psychological, social and legal risk. 
• Proper consent will be taken. 
• Privacy of the patient will be maintained. 
• No intervention will be used here. 
Utilization of Results: The result of the study may help to standardized protocols of low dose 
prophylaxis in hemophilia A patients. Low dose prophylaxis will save money and reduce 
economic burden of patients and government. The result of the study will be published in 
national and international journals.  
 
Facility: The study will be conducted in department of hematology and BMT unit, DMCH. Co-
investigators will be responsible for maintaining patient follow up and data collection. Team of 
volunteer doctor and nurse will be responsible for managing any clinical emergency of the 
patients. The drugs will be stored in our department. APTT (investigation) will be done in our 
laboratory.  
 
 
 

References 
1. Franchini, M., Marano, G., Pati, I., Candura, F., Profili, S., Veropalumbo, E., et al., 2019. 
Emicizumab for the treatment of haemophilia A: a narrative review. Blood Transfusion, 
17(3), p.223-228. 
2. Rodriguez-Merchan, E.C., 2010. Musculoskeletal complications of hemophilia. HSS 
Journal®, 6(1), pp.37-42. 
3. Valentino, L.A., 2010. Blood-induced joint disease: the pathophysiology of hemophilic 
arthropathy. Journal of Thrombosis and Haemostasis. 8(9), pp.1895–1902. 
4. Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al. WFH 
Guidelines for the management of hemophilia, 3rd edition. Haemophilia. (2020) 26:1–
158. doi: 10.1111/hae.14046. 
5. Rabeea Munawar Ali , Madiha Abid , Sidra Zafar , Muhammad Shujat Ali , Rukhshanda 
Nadeem, Raheel Ahmed , Munira Borhany, 2023; Management of Severe Hemophilia A: 
Low-Dose Prophylaxis vs. On-Demand Treatment, National Library of Medicine, 
PMID: 37546069, PMCID: PMC10402932, DOI: 10.7759/cureus.41410 
6. Rodriguez, V., Mancuso, M.E., Warad, D., Hay, C.R.M., DiMichele, D.M., Valentino, 
L., Kenet, G. and Kulkarni, R., 2015. Central venous access device (CVAD) 
complications in Haemophilia with inhibitors undergoing immune tolerance induction: 
lessons from the international immune tolerance study. Haemophilia, 21(5), pp.e369-
e374. 
7. Gouw, S.C., Van Der Bom, J.G., Ljung, R., Escuriola, C., Cid, A.R., Claeyssens-
Donadel, S., Van Geet, C., Kenet, G., Mäkipernaa, A., Molinari, A.C. and Muntean, W., 
2013. Factor VIII products and inhibitor development in severe hemophilia A. New 
England Journal of Medicine, 368(3), pp.231-239 
8. Calvez, T., Chambost, H., Claeyssens-Donadel, S., d’Oiron, R., Goulet, V., Guillet, B., et 
al., 2014. Recombinant factor VIII products and inhibitor development in previously 
untreated boys with severe hemophilia A. Blood, The Journal of the American Society of 
Hematology, 124(23), pp.3398-3408. 
9. Shima, M., Hanabusa, H., Taki, M., Matsushita, T., Sato, T., Fukutake, K., Kasai, R., 
Yoneyama, K., Yoshida, H. and Nogami, K., 2017. Long-term safety and efficacy of 
emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors. 
Blood advances, 1(22), pp.1891-1899. 
10. Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, et al. Factor VIII—
mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med. 
(2016) 374:2044–53. doi: 10.1056/nejmoa1511769. 
11. Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, et 
al.Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. (2017) 
377:809–18. doi: 10.1056/nejmoa1703068. 
 

12. Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, et al. 
Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J 
Med. (2018) 379:811–22. doi: 10.1056/nejmoa1803550. 
13. Young G, Liesner R, Chang T, Sidonio R, Oldenburg J, Jiménez-Yuste V, et al. A 
multicenter, open-label phase 3 study of emicizumab prophylaxis in children with 
hemophilia 
A 
with 
inhibitors. 
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(2019) 
134:2127–38. 
doi: 
10.1182 
blood.2019001869. 
14. Pipe SW, Shima M, Lehle M, Shapiro A, Chebon S, Fukutake K, et al. Efficacy, safety, 
and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with 
haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. 
Lancet Haematol. (2019) 6:e295–305. doi: 10.1016 
15. Kitazawa T, Igawa T, Sampei Z, et al. A bispecific antibody to factors IXa and X restores 
factor VIII hemostatic activity in a hemophilia A model.Nat Med. 2012;18(10):1570-
1574. 
16. Kitazawa T, Esaki K, Tachibana T, et al. Factor VIIIa-mimetic cofactor activity of a 
bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to 
bridge the antigens. Thromb Haemost. 2017;117(7):1348-1357. 
17. Tang ASO, Leong TS, Ko CT, Chew LP. Efficacy of reduced-dose emicizumab in 
haemophilia A with inhibitors: real world experience in East Malaysia. Res Pract Thromb 
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2021 
https://abstracts.isth.org/abstract/efficacy-ofreduced-dose-emicizumab-in-haemophilia-a-
with-inhibitors-realworld-experience-in-east-mal. 
18. Chuansumrit A, Sirachainan N, Jaovisidha S, Jiravichitchai T, Kadegasem P, Kempka K, 
Panuwannakorn M, Rotchanapanya W, Nuntiyakul T. Effectiveness of monthly low dose 
emicizumab prophylaxis without 4-week loading doses among patients with haemophilia 
A with and without inhibitors: A case series report. Haemophilia. 2023 Jan;29(1):382-
385. doi: 10.1111/hae.14707. Epub 2022 Nov 29. PMID: 36446746. 
19. Oldenburg, J., Yan, S., Maro, G., Krishnarajah, G., & Tiede, A. (2020). Assessing 
bleeding rates, related clinical impact and factor utilization in German hemophilia B 
patients treated with extended half-life rIX-FP compared to prior drug therapy. Current 
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https://doi.org/10.1080/03007995.2019.1662675 
 
 
 

Work schedule 
 
 
Activity ↓    (months → ) 
1st 
2nd 3rd 4th 
5th 
6th 
7th 8th 9tth 
10th 11th 12th 
Literature review 
 
 
 
 
 
 
 
 
 
 
 
 
Study design and protocol 
writing 
 
 
 
 
 
 
 
 
 
 
 
 
IRB clearance 
 
 
 
 
 
 
 
 
 
 
 
 
Patient selection and 
enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
Collection of data 
 
 
 
 
 
 
 
 
 
 
 
 
Data cleaning, editing,  
 
 
 
 
 
 
 
 
 
 
 
 
Data analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 Preparing result and 
writing for publication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Budget 
 
 
 
Total: Four lakh Taka only (Tk. /-) 
 
Literature review and Study Design, Protocol writing 
and Ethical Approval 
: 20,000/- 
Data Collection, Data Entry 
: 20,000/- 
Data Cleaning and Editing  
: 10,000/- 
Data Analysis 
: 10,000/- 
Report Writing 
: 10,000/- 
Materials and Supplies 
: 20,000/- 
Internet Access  
: 10,000/- 
Drugs for the study 
: Government supply and WFH 
supported  
Total 
: 1,00,000/- 
 
 
 
 
 
 
 
 
 
 
 

 
Consent form (English) 
 
1. Title of the study: ‘Comparison of Low Dose Emicizumab and Low Dose Factor VIII as a 
Prophylaxis in Hemophilia A patient- a randomized control trial’. 
 
2. Place of the study: Department of Haematology and Bone Marrow Transplantation Unit, Dhaka 
Medical College & Hospital, Dhaka 
 
3. Name of the researcher: Prof. Dr. Akhil Ranjan Biswas. 
 
4. Purpose of the study: The study will be conducted to evaluate the comparison between low dose 
factor VIII prophylaxis and low dose Emicizumab of prophylaxis in preventing bleeding events in 
Haemophilia A. 
 
5. Study population: Patients with Haemophilia A attending the Department of Haematology and Bone 
Marrow Transplant Unit, Dhaka Medical College and Hospital (DMCH), Dhaka. 
 
6. Data provider: Patients or patient’s attendants. 
 
7.  Expectation from the participants: You will be asked some questions regarding the patient and some 
tests will be done. Hope you will help in this process. 
 
8. Risks & discomforts: It is to inform you that in this research you will not face any serious risk 
regarding the study.  
 
9. The benefit of participant in the research: You can benefit from taking part in this study. The drugs 
can effectively reduce your bleeding events improve your quality of life. This study will also be helpful 
for the physicians of Bangladesh to choose more effective prophylactic agent using limited resource. 
 
10. Alternatives: The normal treatment of you will proceed as per the general treatment procedure of the 
hospital, even if you do not participate in the research.pro 
 
11. Incentives: You will not be provided any incentives to take part in this research. Your participation is 
likely to help us to acquire more knowledge about this disease which may be of benefit to other patients 

of our country. The intervention drug will be supplied free of cost by the Govt. of the peoples’ Republic 
of Bangladesh and the World Federation of Haemophilia (WFH) . 
12. Confidentiality: The information that we will collect from this research project will be kept 
confidential unless permitted by you.  
 
13. Voluntary participation: Participation in this research work is fully voluntary work. You can 
withdraw yourself at any stage of this research work. By signing in this informed consent form you will 
not be deprived from any legal rights. 
 
14. Related questions: Please let us know if you have any question. We will try to answer your question 
at our level best. If you feel like throwing any question in future, then you may contact with researcher. 
 
Prof. Dr. Akhil Ranjan Biswas: Mobile no. 01712290706.  
 
 
 
 
 
 
 
 
 
 

If you agree to participate in this study, please sign the attached consent form. 
 
 
INFORMED CONSENT FORM 
 
I,  Mr./Mrs./Miss ......................................................................., here by giving informed consent 
willingly (to allow the patient under my care) to participate in the study to be conducted by Prof. 
Dr. Akhil Ranjon Biswas. Professor and Head, Department of Hematology, Dhaka Medical 
College Hospital, Dhaka without any prejudice. I am fully convinced that during study I (or my 
patient) will not suffer from any serious physical or psychological problems. I am also informed 
that this study was carried out in the developed countries safely and my participation will bring 
fruitful result that will be beneficial for most patients in our country. I have right to withdraw 
myself (or my patient) from this study at any time. I (or the patient) will not receive any financial 
benefit. I have understood that the personal information, medical records and laboratory test 
results of mine (or the patient) will be kept strictly confidential and will be used for research 
purpose only.   
 
 
 
.............................................. 
Signature/Thumb impression of 
participant/guardian 
.................................... 
Signature/Thumb 
impression of witness 
.................................. 
Signature of Researcher 
 
 

Assent form (English) 
 
Title of the study: ‘Comparison of Low Dose Emicizumab and Low Dose Factor VIII as a 
Prophylaxis in Hemophilia A patient’ 
My name is Prof. Akhil Ranjon Biswas. I am head of the Department of Haematology & BMT at Dhaka 
Medical College Hospital, Dhaka. I am inviting you to participate in a research study titled- 
‘Comparison of Low Dose Emicizumab and Low Dose Factor VIII as a Prophylaxis in 
Hemophilia A patient’  
 
Your guardian knows about this study, and gave permission for you to be involved. If you agree, I will 
ask you some of your personal data and some data about the disease you are suffering from.  
 
You do not have obligation to participate in the study.  No one will be bad at you if you decide not to 
participate in this study. Even if you start the study, you can stop later if you want. You may ask 
questions about the study at any time. If you decide to be in the study, I will not tell anyone else how you 
respond or act as part of the study. Even if your parents or teachers ask, I will not tell them about what 
you say or do in the study. Signing here means that you have read this form or have had it read to you and 
that you are willing to be in this study 
           
.............................................. 
Signature/Thumb impression of 
participant 
.................................... 
Signature/Thumb impression 
of guardian 
.................................. 
Signature of Researcher 
 
 
 
 
 
 
 

Case Record Form 
Title: ‘Efficacy of Low Dose Emicizumab vs Low Dose Factor VIII Prophylaxis in Severe 
and Moderate Hemophilia A patient’. 
 
 
 
General Information:                                    Randomization Number-   
Factor level-              
Date of Inves-  
Age of first bleeding-  
Age at diagnosis-   
 
Target Joint- Number- 
Specify-  
Blood Group-            Wt-         Ht-   
Inhibitor status-  
Result and date of investigations-  
Address:  Village _ _ _ _ _ _ _ _ _ _ _ _  
                 Upazilla _ _ _ _ _ _ _ _ _ _ _ _ 
Union _ _ _ _ _ _ _ _ _ _ _ 
District _ _ _ _ _ _ _ _ _ _ _ _ 
Educational status 
• Patient  
• Guardian 
 Illiterate  
 Primary 
 SSC 
 HSC 
 Graduate 
 Postgraduate 

Emicizumab Group- I and WI 
 
1st 
week 
2nd 
week 
3rd 
week 
4th 
week 
8th 
week 
12th 
week 
16th 
week 
20th  
week 
24th 
week 
28th 
week 
Episodes of bleeding 
 
 
 
 
 
 
 
 
 
 
Episodes of Joint 
bleeding 
 
 
 
 
 
 
 
 
 
 
Episodes of 
Spontaneous bleeding 
 
 
 
 
 
 
 
 
 
 
APTT 
 
 
 
 
 
 
 
 
 
 
Weight  
 
 
 
 
 
 
 
 
 
 
Dose 
 
 
 
 
 
 
 
 
 
 
 
Factor VIII Group follow up 
 
1st 
week 
2nd 
week 
3rd 
week 
4th 
week 
5th 
week 
6th 
week 
7th 
week 
8th  
week 
Episodes of bleeding 
 
 
 
 
 
 
 
 
Episodes of Joint bleeding 
 
 
 
 
 
 
 
 
Episodes of Spontaneous 
bleeding 
 
 
 
 
 
 
 
 
APTT 
 
 
 
 
 
 
 
 
Weight  
 
 
 
 
 
 
 
 
 
Dose 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
9th  
week 
10th  
week 
11th  
week 
12th 
week 
13th 
week 
14th 
week 
15th 
week 
16th 
week 
Episodes of bleeding 
 
 
 
 
 
 
 
 
Episodes of Joint bleeding 
 
 
 
 
 
 
 
 
Episodes of Spontaneous 
bleeding 
 
 
 
 
 
 
 
 
APTT 
 
 
 
 
 
 
 
 
Weight  
 
 
 
 
 
 
 
 
 
Dose 
 
 
 
 
 
 
 
 
 
 
 
17th  
week 
18th  
week 
19th  
week 
20th  
week 
21th 
week 
22th 
week 
23th 
week 
24th  
week 
Episodes of bleeding 
 
 
 
 
 
 
 
 
Episodes of Joint bleeding 
 
 
 
 
 
 
 
 
Episodes of Spontaneous 
bleeding 
 
 
 
 
 
 
 
 
APTT 
 
 
 
 
 
 
 
 
Weight  
 
 
 
 
 
 
 
 
 
Dose 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
25th  
week 
26th  
week 
27th  
week 
28th  
week 
Episodes of bleeding 
 
 
 
 
Episodes of Joint bleeding 
 
 
 
 
Episodes of Spontaneous 
bleeding 
 
 
 
 
APTT 
 
 
 
 
Weight  
 
 
 
 
 
Dose 
 
 
 
 
 
 
 
 
Interview Conducted By- 
Name – 
Sign-  
 
 

Randomization Plan 
 
Group 
Code 
Name 
1 
Factor VIII Group  
VJ8 
 
2 
Emicizumab Group (with inhibitor)  
QD7 
 
3 
Emicizumab Group (without inhibitor)  
XY8 
 
4 
Emicizumab Group (with inhibitor)  
VN2 
 
5 
Factor VIII Group 
AA2 
 
6 
Factor VIII Group  
HH2 
 
7 
Emicizumab Group (with inhibitor) 
JC1 
 
8 
Emicizumab Group (without inhibitor),  NB1 
 
9 
Factor VIII Group              
QT5 
 
10 
Emicizumab Group (with inhibitor)  
RG0 
 
11 
Factor VIII Group        
MO9 
 
12 
Factor VIII Group             
AM0 
 
13 
Emicizumab Group (with inhibitor)  
KX8 
 
14 
Factor VIII Group              
CC0 
 
15 
Emicizumab Group (without inhibitor),  CU6 
 
16 
Factor VIII Group 
XX9 
 
17 
Factor VIII Group        
PW2 
 
18 
Emicizumab Group (without inhibitor) 
EK9 
 
19 
Emicizumab Group (with inhibitor)  
KQ3 
 
20 
Factor VIII Group  
VJ8 
 
 
 
 

Put Tick sign (√) appropriate answers against each of the following statement 
 (If not Applicable, please write NA) 
                                     
Sign of the Principal Investigator 
1. Source of Population:  
4. Are subjects clearly informed about: 
  (a) Ill Subject 
√Yes 
No 
(a) Nature and purpose of    
Study 
√Yes 
No 
 (b) Non-ill Subject 
Yes 
√No 
(b) Procedures to be followed    
   including alternatives used 
√Yes 
No 
  (c) Minors or persons under        
guardianship 
√Yes 
No 
  (c) Physical risks 
√Yes 
No 
2. Does the study Involve:  
 
 
 (d) Private questions 
√Yes 
No 
 (a) Physical risks to subjects 
√Yes 
No 
 (e) Invasion of the Body 
√Yes 
No 
 (b) Social Risks 
Yes 
√No 
 (f) Benefits to be derived  
√Yes 
No 
  (c) Psychological risks to         
subjects 
√Yes 
No 
 (g) Rights to refuse to participate or 
to withdraw from study 
√Yes 
No 
 (d) Discomfort to subjects 
√Yes 
No 
 (h) Confidential handling of data 
√Yes 
No 
 (e) Invasion of the body 
√Yes 
No 
 (i) Compensation where there are 
risks or loss of working time or 
privacy is involved in any particular 
procedure  
√Yes 
No 
 (f) Invasion of Privacy 
Yes 
√No 
5. Will signed consent form/verbal consent be 
required:  
 (g) Disclosure of information 
damaging to subject or others 
Yes 
√No 
 (a) From Subjects 
√Yes 
No 
3. Does the study involve:  
 
 
 (b) From parent or guardian (if 
subjects are minors)  
√Yes 
No 
 (a) Use of records (hospital, 
medical, death, birth or other) 
√Yes 
No 
6. Will precautions be taken to protect 
anonymity of subjects 
√Yes 
No 
 (b) Use of fetal tissue or        
abortus 
Yes 
√No 
 
 
 
  (c) Use of organs or body        
fluids 
Yes 
√No