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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia B
• Intervention / Treatment: Drug: BENEFIX

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100032
    • Peking Union Medical College Hospital
  • Beijing, China, 100045
    • Hematology Department,Beijing Children's Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BeneFIX	Drug: BENEFIX; Single dose of 50 IU/kg of BeneFIX by intravenous infusion within 10 minutes.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: August 7, 2014
• First Submitted That Met QC Criteria: August 7, 2014
• First Posted (Estimate): August 11, 2014

Study Record Updates

• Last Update Posted (Estimate): July 25, 2016
• Last Update Submitted That Met QC Criteria: June 13, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: B1821048; 2015-003027-61 (EudraCT Number)