AKATSUKI Study

JRCT ID: jRCTs041200037

Registered date:03/08/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Congenital hemophilia A with FVIII inhibitors
• Date of first enrollment: 06/11/2020
• Target sample size: 15
• Study type: Interventional

Intervention(s)

Any type of FVIII concentrate can be used for ITI but the dosing regimen must be 50 IU/kg three times a week. However, when using extended half-life FVIII concentrates, a dosing frequency of twice a week will be permitted.
Patients who achieve the partial success during the study will subsequently receive emicizumab prophylaxis and FVIII concentrate starting from the date of their next scheduled study visit following investigator confirmation of partial success. Any type of FVIII concentrate can be used for treatment after partial success but dosing regimen must be 50 IU/kg. FVIII concentrates will be administered once a week for the first 24 weeks, and once every 2-week for further 24 weeks. After 48 weeks, investigators can decide to stop of administer of FVIII concentrates. The dose of FVIII concentrate may also be adjusted by +-20%.
FVIII inhibitor titer and FVIII activity will be assessed once in 4 weeks. Patients who achieve the partial success during the study will be assessed once in 12 weeks.

Outcome(s)

Primary Outcome

To comprehensively evaluate the following safety of emicizumab under and after ITI in patients with congenital hemophilia A with FVIII inhibitors.
- Adverse event (Mainly thromboembolic events)
- Abnormal laboratory values

Secondary Outcome

- Number of bleeds over time requiring treatment with coagulation factor products
- Number of patients meeting partial success of responsiveness to ITI therapy
- Time to achieve negative FVIII inhibitor titers and partial success in patients starting ITI after study enrollment
- FVIII inhibitor titers under and after ITI therapy
- Patient health-related quality of life (HR-QoL) as measured by Hemophilia-Specific Quality of Life Short Form (Haemo-QoL-SF) and caregiver HR-QoL as measured by Inhibitor-Specific Quality of Life with Aspects of Caregiver Burden (Adapted INHIB-QoL) scores

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients must meet all of the following criteria for study entry:
1) Informed Consent Form signed by the patient or the patient's legally authorized representative. Pediatric patients who are capable: Informed Assent Form signed by the patient
2) Patient or caregiver: Willing and able to comply with all study procedures (including filling out questionnaires on bleeds/drugs used)
3) Diagnosed with congenital hemophilia A and meets either of the following criteria:
a. Will start ITI after study enrollment and has positive FVIII inhibitor titer ( >= 0.6 BU/mL) as evidenced by most recent titer results within 8 weeks before enrollment
b. Is already undergoing ITI at study enrollment and has not yet met partial success as evidenced by most recent titer results within 8 weeks before enrollment

Exclude criteria

Patients who meet any of the following criteria will be excluded from study entry:
1) Inherited or acquired bleeding disorder other than congenital hemophilia A
2) Previous (within the last 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or high risk for thromboembolic diseases(e.g. protein S deficiency)
3) At high risk for thrombotic microangiopathy (TMA) in the opinion of the investigator based on previous or familial history of TMA (e.g., thrombotic thrombocytopenic purpura [TTP], atypical hemolytic uremic syndrome [aHUS])
4) Participating or planning to participate in other intervention trials
5) Otherwise unsuitable for study participation in the opinion of the investigator

Related Information

• Primary Sponsor: Matsushita Tadashi
• Secondary Sponsor: Nishi Kazuhiko,Chugai Pharmaceutical Co., Ltd