Safety, Efficacy Evaluation of Recombinant Coagulation Factor VIII Injection in Subjects With Hemophilia A.

Study Overview
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Brief Summary
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This is a multi-center, open-label, single-arm trial to evaluate the efficacy and safety of Recombinant Coagulation Factor VIII in patients with hemophilia A . Recombinant Coagulation Factor VIII is prophylactic administrated 25 - 35 IU/kg once every other day or three times per week which should be continuous for 24 weeks.

Official Title
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Multicenter, Noncontrol Study of Recombinant Coagulation Factor VIII for Prophylactic Therapy in Subjects With Hemophilia A.

Conditions
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Hemophilia A

Intervention / Treatment
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* Drug: Recombinant Human Coagulation FVIII


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hemophilia A. FVIII:C <1%. 3）12 and 65 years old. 4）Has received FVIII treatment and the treatment exposure days ≥100. 5）Has bleeding treatment records of at least 3 months before randomization. 6）FVIII inhibitor assay results is negative. 7） Subjects should agree to use an adequate method of contraception during the study. 8）Understood and Signed an informed consent form. Exclusion Criteria: Has a history or family history of blood coagulation factor VIII inhibitor. Has other coagulation dysfunction diseases in addition to hemophilia A. HIV positive. Plan to receive surgery during the trial. Has used immunomodulator within one weeks before the first dose，and less than 7 half-life periods. Known to be allergic to experimental drugs or any excipients. Severe anemia and need blood transfusion. Serious liver or kidney damage. Serious heart disease. Uncontrollable hypertension. Has participated in other clinical studies within one month before the first dose. The researchers believe that it is not suitable for participants.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prophylactic therapy<br>Subjects received Recombinant Human Coagulation FVIII for prophylactic therapy with 25 - 35 IU/kg injection once every other day or three times per week for 6 months. | Drug: Recombinant Human Coagulation FVIII<br>* A kind of Recombinant Coagulation Factor VIII Injection produced by sponsor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized joint bleeding rate | Annualized joint bleeding rate（AJBR） can be calculated using the following formula: Number of joint bleeding events during efficacy evaluation period/(number of days in treatment period/365.25). | up to 24 weeks | 
| Incremental Recovery of the First Dose | Peak activity of FVIII (as Cmax) measured within 1 hour after the end of injection | After the first dose on day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Event Treatment Efficacy | The investigator shall evaluate the hemostatic effect after the treatment of every bleeding event of subjects based on a four-point scale(excellent, good, moderate, not relieved). | up to 24 weeks | 
| Monthly Average Number of Bleedings | Number of bleeding events in each month. | up to 24 weeks | 
| The number and dose of injection of Recombinant Human Coagulation FVIII required per bleeding episode | The number and dose of injection of Recombinant Human Coagulation FVIII required per bleeding episode | up to 24 weeks | 
| Incremental Recovery of Duplicated Dose | Peak activity of FVIII (as Cmax) measured within 1 hour after the end of injection. | up to 12 weeks, 24 weeks | 
| Hemophilia Joint Health Score (HJHS) | The scale assesses the functional status of the six major joints of the elbow, knee, and ankle, including: joint swelling, swelling duration, muscle atrophy, muscle strength, joint friction, joint pain, joint extension, joint flexion Degree decline, overall gait, etc. | Baseline, week 24 | 
| Assess the impact of Recombinant Human Coagulation FVIII following Patient Reported Outcome (PRO) EQ-5D | EQ-5D is a general questionnaire designed to measure health status on a scale of 0-100 with the higher value representing a better outcome and record the participants' current health state in 5 domains mobility, selfcare, usual activities, pain, anxiety. | Baseline, week 24 |