Low-dose ITI Strategy for Children in Hemophilia A With High-titer Inhibitor and Poor ITI Risk in China

Phase 4

• Conditions: Hemophilia A With Inhibitor
• Interventions: Drug: Coagulation Factor VIII; Drug: Prednisone; Drug: Rituximab

• Registration Number: NCT03598725
• Lead Sponsor: Beijing Children's Hospital

Brief Summary

The study start on January 18, 2017. The Severe(FⅧ\<1%) and moderate hemophilia A (FⅧ1%～5%)children with high titer inhibitor(historical peak inhibitor titer≥5BU ) combining with poor ITI risk(s) were enrolled. The low-dose ITI was alone or combined with immunosuppression.

Detailed Description

Poor risk(s) includes:①peak historical inhibitor titer≥200BU ②inhibitor titer≥10BU before ITI initiation ③peak inhibitor titer during ITI≥200BU ④time to titer decline to\<10BU before ITI≥24 months ⑤age≥8 years at start of ITI ⑥ITI initiated ≥5 years after inhibitor diagnosis ⑦interruptions in ITI≥2 weeks in duration. The low-dose ITI strategy consist of FⅧ（25-50IU/kg）alone or combining with immunosuppression: prednisone and Rituximab when the inhibitor titer ≥40BU ml/ml before or during ITI.

Study Timeline

• Study Start: 2016-01-01
• Study First Submitted: 2018-01-23
• Status Verified: 2018-07
• Study First Submitted QC: 2018-07-23
• Last Update Submitted: 2018-07-23
• Study First Posted: 2018-07-26
• Last Update Posted: 2018-07-26
• Primary Completion: 2019-12-01
• Study Completion: 2020-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 55

Inclusion Criteria

• Males
• from 1 to 14 years old
• severe or moderate hemophilia A;
• inhibitors positive before ITI started.

Exclusion Criteria

• Females
• <1 or >14 years old
• hemophilia B or mild haemophilia A;
• inhibitor negative before ITI started.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ITI strategy	Coagulation Factor VIII	The low-dose ITI was Coagulation Factor VIII (50IU/kg, every other day) alone or combined with prednisone (2mg Kg-1/day, one month, then taper in three months) depending on the tendency of inhibitor, and Rituximab (375mg/square meter every week for 4 weeks) when the inhibitor titer ≥40BU/ml before or during ITI.Inhibitor and hemorrhage should be retested and recorded periodically.
ITI strategy	Rituximab	The low-dose ITI was Coagulation Factor VIII (50IU/kg, every other day) alone or combined with prednisone (2mg Kg-1/day, one month, then taper in three months) depending on the tendency of inhibitor, and Rituximab (375mg/square meter every week for 4 weeks) when the inhibitor titer ≥40BU/ml before or during ITI.Inhibitor and hemorrhage should be retested and recorded periodically.
ITI strategy	Prednisone	The low-dose ITI was Coagulation Factor VIII (50IU/kg, every other day) alone or combined with prednisone (2mg Kg-1/day, one month, then taper in three months) depending on the tendency of inhibitor, and Rituximab (375mg/square meter every week for 4 weeks) when the inhibitor titer ≥40BU/ml before or during ITI.Inhibitor and hemorrhage should be retested and recorded periodically.

Primary Outcome Measures

Name	Time	Method
Success rate	2 years	Success rate

Secondary Outcome Measures

Name	Time	Method
Annualized Bleeding Rate	2 year	How many times for all types of bleeding
Success time	2 years	How long to success
Annualized Joint Bleeding Rate	2 year	How many times for joint bleeding

Trial Locations

Locations (1)

Beijing Children's Hospital; 🇨🇳 Beijing, Beijing, China