Trial Outcomes & Findings for An Open-Label, Single Dose Pharmacokinetic Study of Benefix (Recombinant Factor IX) in Male Chinese Subjects With Hemophilia B (NCT NCT02213250)

NCT ID: NCT02213250

Last Updated: 2016-07-25

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
• Results posted on: 2016-07-25

Participant Flow

Twelve (12) participants that were age 6 years or older (weight ≥20 kg) with moderate severe to severe hemophilia B (FIX activity ≤2%) were enrolled. Four (4) participants were at the younger age range of ≥6 and <12 years; remaining participants were 12 years or older.

Participants did not receive an infusion of any FIX products for at least 4 days and were required to be in a non-bleeding state before the administration of BeneFIX on Day 1.

Participant milestones

Measure	BeneFIX 50 IU/kg; Age Group: >=6 and <12 Years Participants received a single dose of 50 IU/kg BeneFIX administered by intravenous (IV) infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group: >=12 Years Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Overall Study STARTED	4	8
Overall Study COMPLETED	4	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	All Participants n=12 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Age, Continuous	24.8 Years STANDARD_DEVIATION 15.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The pharmacokinetics (PK) parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Maximum Observed Plasma Concentration (Cmax)	0.3880 IU/milliliter (IU/mL) Geometric Coefficient of Variation 26	0.4226 IU/milliliter (IU/mL) Geometric Coefficient of Variation 16

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Area Under the Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)	6.930 IU*hour/milliliter (IU*hr/mL) Geometric Coefficient of Variation 18	9.707 IU*hour/milliliter (IU*hr/mL) Geometric Coefficient of Variation 15

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Area Under the Concentration Time Curve From Time 0 to Infinity (AUCinf)	7.841 IU*hr/ml Geometric Coefficient of Variation 16	11.66 IU*hr/ml Geometric Coefficient of Variation 15

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Time to Reach Cmax (Tmax)	0.500 hours Interval 0.25 to 3.0	0.375 hours Interval 0.25 to 3.0

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

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.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Volume of Distribution at Steady State (Vss)	227.9 milliliter/kilogram (mL/kg) Geometric Coefficient of Variation 20	218.8 milliliter/kilogram (mL/kg) Geometric Coefficient of Variation 19

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

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.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Terminal Phase Rate Constant (Kel)	0.02509 1/hr Geometric Coefficient of Variation 16	0.01781 1/hr Geometric Coefficient of Variation 20

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

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.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Mean Residence Time (MRT)	35.78 hours Geometric Coefficient of Variation 14	51.01 hours Geometric Coefficient of Variation 16

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Plasma Decay Half-Life (t½)	27.88 hours Standard Deviation 4.4903	39.56 hours Standard Deviation 7.3832

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Systemic Clearance (CL)	6.378 mL/hr/kg Geometric Coefficient of Variation 16	4.291 mL/hr/kg Geometric Coefficient of Variation 15

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5 and 1 hour post-dose

Population: The PK parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the PK parameters of primary interest. All participants were included in the PK analysis population.

Incremental recovery: Increase in circulating increase in FIX activity for every IU of BeneFIX administered per kg of body weight.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=4 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years n=8 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Incremental Recovery	0.7759 (IU/dL)/(IU/Kg) Geometric Coefficient of Variation 26	0.8199 (IU/dL)/(IU/Kg) Geometric Coefficient of Variation 17

SECONDARY outcome

Timeframe: From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug.

Population: The safety analysis set was defined as all participants who received at least 1 dose of BeneFIX.

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.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=12 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Withdrawals Due to Adverse Events (AE)	0 Particpants	—

SECONDARY outcome

Timeframe: Baseline up to 96 hours post-dose (Day 5 or early termination)

Population: The safety analysis population included All participants who received at least 1 dose of BeneFIX.

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.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=12 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Number of Participants With Abnormal Clinical Laboratory Measurements (Without Regard to Baseline Abnormality)	12 Participants	—

SECONDARY outcome

Timeframe: Baseline up to 96 hours post-dose (Day 5 or early termination)

Population: The safety analysis population included All participants who received at least 1 dose of BeneFIX.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=12 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Number of Participants With Vital Signs Post-Dose Data Met Criteria of Potential Clinical Concern (Without Regard to Baseline Abnormality)	1 Participants	—

SECONDARY outcome

Timeframe: From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug.

Population: The safety analysis population included All participants who received at least 1 dose of BeneFIX.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=12 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Number of Participants With Inhibitor Development	0 Participants	—

SECONDARY outcome

Timeframe: From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug.

Population: The safety analysis population included All participants who received at least 1 dose of BeneFIX.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=12 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Number of Participants With Allergic Reactions	0 Participants	—

SECONDARY outcome

Timeframe: From the subject provided informed consent through and including 28 calendar days after the last administration of the study drug.

Population: The safety analysis population included All participants who received at least 1 dose of BeneFIX.

Outcome measures

Measure	BeneFIX 50 IU/kg; >=6 and <12 Years n=12 Participants Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.	BeneFIX 50 IU/kg; Age Group:>=12 Years Participants received a single dose of 50 IU/kg BeneFIX administered by IV infusion within 10 minutes at approximately 0800 hours (±2 hours) on Day 1.
Number of Subjects With Thrombogenicity	0 Participants	—

Adverse Events

BeneFIX 50 IU/kg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc

Phone: (001)8007181021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Restriction Description: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER