An Open-Label, Single Dose Pharmacokinetic Study of Benefix (Recombinant Factor IX) in Male Chinese Subjects With Hemophilia B

Study Overview
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Brief Summary
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The sample size of 12 male Chinese subjects are based on the CFDA requirement for a China PK study and to support the registration in China.

Official Title
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An Open-label, Single Dose Pharmacokinetic Study Of Benefix (Nonacog Alfa, Recombinant Factor Ix) In Male Chinese Subjects With Hemophilia B

Conditions
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Hemophilia B

Intervention / Treatment
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* Drug: BENEFIX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Chinese subjects 6 years or older (weight ≥20kg) with moderate to severe hemophilia B (Factor IX activity ≤2%). Subjects should not have received an infusion of any Factor IX products for at least 4 days before the administration of BeneFIX on Day 1. Subjects must be in a non-bleeding state before the administration of BeneFIX on Day 1. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) disease or clinical findings at Screening. Diagnosed with any other bleeding disorder in addition to hemophilia B. Current FIX inhibitor or history of FIX inhibitor (defined as > Upper Limit of Normal (ULN) of the reporting lab).

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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Male

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BeneFIX<br> | Drug: BENEFIX<br>* Single dose of 50 IU/kg of BeneFIX by intravenous infusion within 10 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Area Under the Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) |  | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Area Under the Concentration Time Curve From Time 0 to Infinity (AUCinf) |  | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Time to Reach Cmax (Tmax) |  | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Volume of Distribution at Steady State (Vss) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steady-state. | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Terminal Phase Rate Constant (Kel) | Linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Mean Residence Time (MRT) | AUMCinf/AUCinf, where AUMCinf is the area under the first moment curve from time 0 extrapolated to infinite time, calculated using the linear/log trapezoidal method. | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Plasma Decay Half-Life (t½) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Systemic Clearance (CL) | CL is a quantitative measure of the rate at which a drug substance is removed from the body. | Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose | 
| Incremental Recovery | Incremental recovery: Increase in circulating increase in FIX activity for every IU of BeneFIX administered per kg of body weight. | Pre-dose, 0.25, 0.5 and 1 hour post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Withdrawals Due to Adverse Events (AE) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAE is defined as newly occurring or worsening after first dose. | From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug. | 
| Number of Participants With Abnormal Clinical Laboratory Measurements (Without Regard to Baseline Abnormality) | Clinical laboratory analysis tests included hematology, serium chemistry, prothrombin time and urianalysis. Numbers of subjects with laboratory test abnormalities without regard to baseline abnormality were reported. | Baseline up to 96 hours post-dose (Day 5 or early termination) | 
| Number of Participants With Vital Signs Post-Dose Data Met Criteria of Potential Clinical Concern (Without Regard to Baseline Abnormality) |  | Baseline up to 96 hours post-dose (Day 5 or early termination) | 
| Number of Participants With Inhibitor Development |  | From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug. | 
| Number of Participants With Allergic Reactions |  | From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug. | 
| Number of Subjects With Thrombogenicity |  | From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug. |