Low Dose Emicizumab vs Low Dose Factor VIII in Prophylaxis in Hemophilia A Patients

NCT ID: NCT06938659

Last Updated: 2025-04-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-01

Study Completion Date

2026-07-31

Brief Summary

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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. This study intends 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, it is possible to 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 and it is convenient for administration due to less frequent and subcutaneous administration. 20 severe hemophilia A patients will be selected randomly from interested patients for this study. 6 patients with inhibitor will be randomized 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. Initial loading dose will be given and the participants will be followed up for 6 months. At the end of the study Annualized bleeding rate (ABR), Annualized joint bleeding rate (AJBR), Annualized spontaneous bleeding rate (ASBR), APTT will be compared among the groups. Inhibitor to factor VIII will also be evaluated after six months in Factor VIII group.

Detailed Description

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Selection criteria for the study- Severe hemophilia A patients with or without inhibitor to factor VIII will be eligible to participate in the study. Patients with inhibitor will not be included in factor VII group.

Sample Size: Sample size is determined by availability of drugs rather than any scientific formula. The investigators can provide Emicizumab to 10 patients for 28 weeks as prophylaxis. So, the investigators intend to include 10 patients in each group.

Sampling technique: The investigators will select 20 severe hemophilia A patients randomly from interested patients. The investigators will randomize 6 patients with inhibitor 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 Variables to be studied- A. Independent variable

1. Socio-demographic variables- Age, Educational status, Weight, Occupation
2. Variables related to Hemophilia- 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 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.

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 rounded to 30mg, 60 mg or any dose nearest to 1 mg/kg when fractionation of vail is possible.

Factor VIII- 10-15 unit/Kg thrice weekly (for conventional half-life products) or twice weekly (for extended half-life products) for 28 weeks. Inj. Factor VIII is available in 250U, 500U, 750U \& 1,000 IU vail sizes. Dose will be round up to full nearest full vail strength.

Follow Up- Participants in Emicizumab group will visit weekly for first 4 week than once in every 4 week for 24 weeks (Total 28 weeks).

Participants in Factor VIII group will visit twice weekly for 28 weeks. Information of data collection sheet will be collected once in a week.

Patient must attend physically for every dose administration. 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.

Primary End Point- This study will include 28 weeks follow up of the patients. Each patient will receive 28 weeks prophylaxis. After that period patients will continue prophylaxis if drugs are available but will not be considered for this study. Otherwise, they will receive on demand treatment in our HTC (hemophilia treatment center).

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.

Conditions

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Hemophilia A

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.

patients with inhibitor (Emicizumab Group-I):

Patients without inhibitor (Emicizumab Group-WI):

Patients without inhibitor (Factor VIII Group).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Emicizumab Group- I

Severe hemophilia A patients with inhibitor

Group Type EXPERIMENTAL

Emicizumab Injection

Intervention Type DRUG

Emicizumab 0.8-1.5mg/kg weekly for 4 weeks as loading dose. Then 0.8-1.5mg/kg 4-weekly for 24 weeks will be used in Emicizumab group-I and Emicizumab Group- WI

Emicizumab Group- WI

Severe hemophilia A Patients without inhibitor (Emicizumab Group):

Group Type EXPERIMENTAL

Emicizumab Injection

Intervention Type DRUG

Emicizumab 0.8-1.5mg/kg weekly for 4 weeks as loading dose. Then 0.8-1.5mg/kg 4-weekly for 24 weeks will be used in Emicizumab group-I and Emicizumab Group- WI

Factor VIII Group

Severe hemophilia A Patients without inhibitor.

Group Type ACTIVE_COMPARATOR

Factor VIII (FVIII)

Intervention Type DRUG

10-15 unit/Kg thrice weekly (for conventional half-life products) or twice weekly (for extended half-life products) for 28 weeks. Inj. Factor VIII is available in 250U, 500U, 750U \& 1,000 IU vail sizes. Dose will be round up to full nearest full vail strength.

Interventions

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Emicizumab Injection

Emicizumab 0.8-1.5mg/kg weekly for 4 weeks as loading dose. Then 0.8-1.5mg/kg 4-weekly for 24 weeks will be used in Emicizumab group-I and Emicizumab Group- WI

Intervention Type DRUG

Factor VIII (FVIII)

10-15 unit/Kg thrice weekly (for conventional half-life products) or twice weekly (for extended half-life products) for 28 weeks. Inj. Factor VIII is available in 250U, 500U, 750U \& 1,000 IU vail sizes. Dose will be round up to full nearest full vail strength.

Intervention Type DRUG

Other Intervention Names

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Hemlibra Afstyla Kovaltry

Eligibility Criteria

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Inclusion Criteria

* Severe hemophilia A patient with or without inhibitor to factor VIII.

Exclusion Criteria

* 1\. Severe hemophilia A patient not willing to participate.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dhaka Medical College

OTHER

Sponsor Role lead

Responsible Party

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Akhil Ranjon Biswas

Professor and Head of the Department of Hematology.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Akhil R. Biswas, MBBS, FCPS

Role: PRINCIPAL_INVESTIGATOR

Dhaka Medical College

Locations

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Dhaka Medical College Hospital

Dhaka, , Bangladesh

Site Status

Countries

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Bangladesh

Central Contacts

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Akhil R. Biswas, MBBS,FCPS

Role: CONTACT

+8801712290706

Gazi Y. Islam, MBBS, FCPS

Role: CONTACT

+8801716715995

References

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Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, Kasai R, Yoneyama K, Yoshida H, Nogami K. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors. Blood Adv. 2017 Sep 27;1(22):1891-1899. doi: 10.1182/bloodadvances.2017006684. eCollection 2017 Oct 10.

Reference Type RESULT
PMID: 29296836 (View on PubMed)

Young G, Liesner R, Chang T, Sidonio R, Oldenburg J, Jimenez-Yuste V, Mahlangu J, Kruse-Jarres R, Wang M, Uguen M, Doral MY, Wright LY, Schmitt C, Levy GG, Shima M, Mancuso ME. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019 Dec 12;134(24):2127-2138. doi: 10.1182/blood.2019001869.

Reference Type RESULT
PMID: 31697801 (View on PubMed)

Xu Y, Wang Y, Wu R, Zheng C, Zhang L, Xu W, Feng X, Wang H, Cao X, He L, Xue T, Jin M, Xie B, Ling J, Sun L, Su R, Cheng H, Fang Y, Poon MC, Liu W, Zhang L, Xue F, Yang R. Reduced doses of emicizumab achieve good efficacy: Results from a national-wide multicentre real-world study in China. Haemophilia. 2024 Jul;30(4):959-969. doi: 10.1111/hae.15062. Epub 2024 Jun 9.

Reference Type RESULT
PMID: 38853005 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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ERC-DMC/ECC/2024/215

Identifier Type: -

Identifier Source: org_study_id

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