Clinical Trial Results:
An Open-Label, Single Dose Pharmacokinetic Study of BeneFIX (Nonacog Alfa, Recombinant Factor IX) in Male Chinese Subjects With Hemophilia B
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Summary
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EudraCT number |
2015-003027-61 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
08 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jun 2016
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First version publication date |
29 Jun 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
B1821048
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02213250 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer, Inc
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Sponsor organisation address |
235 E 42nd Street, New York, United States, 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc, 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc, 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Jun 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
08 Apr 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Apr 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective was to characterize single dose pharmacokinetic profiles of BeneFIX (50 IU/kg) in male Chinese subjects with hemophilia B.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Mar 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
China: 12
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Worldwide total number of subjects |
12
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
4
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
8
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Twelve (12) subjects that were age 6 years or older (weight ≥20 kg) with moderate severe to severe hemophilia B (FIX activity ≤2%) were enrolled. Four (4) subjects were at the younger age range of ≥6 and <12 years; remaining subjects were 12 years or older. | |||||||||
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Pre-assignment
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Screening details |
Subjects 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. | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
12 | |||||||||
Number of subjects completed |
12 | |||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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BeneFIX 50 IU/kg; Age group: >=6 and <12 years | |||||||||
Arm description |
Subjects 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. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
BeneFIX
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
a single of BeneFIX 50 IU/kg by intravenous infusion
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Arm title
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BeneFIX 50 IU/kg; Age group: >=12 years | |||||||||
Arm description |
Subejcts 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. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
BeneFIX
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
a single dose of BeneFIX 50 IU/kg by intravenous infusion
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BeneFIX 50 IU/kg; Age group: >=6 and <12 years
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Reporting group description |
Subjects 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. | ||
Reporting group title |
BeneFIX 50 IU/kg; Age group: >=12 years
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Reporting group description |
Subejcts 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. | ||
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End point title |
Maximum Observed Plasma Concentration (Cmax) [1] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Area Under the Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) [2] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Primary: Area Under the Concentration Time Curve From Time 0 to Infinity (AUCinf) [3] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to Reach Cmax (Tmax) [4] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Volume of Distribution at Steady State (Vss) [5] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Terminal Phase Rate Constant (Kel) [6] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean Residence Time (MRT) [7] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Decay Half-Life (t½) [8] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Systemic Clearance (CL) [9] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5, 1, 3, 6, 9, 24, 50, 72 and 96 hours post-dose
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Incremental Recovery [10] | ||||||||||||
End point description |
The pharmacokinetics (PK) parameter analysis population was defined as all subjects enrolled and treated who had at least 1 of the PK parameters of primary interest. All subjects were included in the PK analysis population.
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End point type |
Primary
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End point timeframe |
Pre-dose, 0.25, 0.5 and 1 hour post-dose
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were done for this end point. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects With Abnormal Clinical Laboratory Measurements (Without Regard to Baseline Abnormality) | |||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Screening, Day 0 and 96 hours post-dose (Day 5 or early termination)
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Subjects With Vital Signs Post-Dose Data Met Criteria of Potential Clinical Concern (Without Regard to Baseline Abnormality) | |||||||||
End point description |
The safety analysis population included All participants who received at least 1 dose of BeneFIX.
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End point type |
Secondary
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End point timeframe |
Screening, pre-dose (baseline) and 96 hours post-dose (Day 5 or early termination)
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| Notes [11] - None of the vital signs values met the criteria for potential clinical concern. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Subjects with inhibitor development | |||||||||
End point description |
The safety analysis population included All subjects who received at least 1 dose of BeneFIX.
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End point type |
Secondary
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End point timeframe |
Screening, Day 0 and 96 hours post-dose (Day 5 or early termination)
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| Notes [12] - There were no subjects with inhibitor development. [13] - There were no subjects with inhibitor development. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Subjects with allergic reactions | |||||||||
End point description |
The safety analysis population included all subjects who received at least 1 dose of BeneFIX.
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End point type |
Secondary
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End point timeframe |
Baseline up to 28 calendar days post the last administration of study drug
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| Notes [14] - There were no subjects with allergic reactions. [15] - There were no subjects with allergic reactions. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of subjects with thrombogenicity | |||||||||
End point description |
The safety analysis population included all subjects who received at least 1 dose of BeneFIX.
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End point type |
Secondary
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End point timeframe |
Day 0 and 96 hours post-dose (Day 5 or early termination)
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| Notes [16] - There were no subjects with thrombogenicity. [17] - There were no subjects with thrombogenicity. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
Baseline up to 28 calendar days post the last administration of study drug (BeneFIX).
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Assessment type |
Non-systematic | |||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
BeneFIX 50 IU/kg; Age group: >=12 years
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Reporting group description |
Subejcts 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. | |||||||||||||||
Reporting group title |
BeneFIX 50 IU/kg; Age group: >=6 and <12 years
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Reporting group description |
Subjects 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. | |||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There were no adverse events reported in this study. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Aug 2014 |
Schedule of activities, Section 3.1, Section 6.2.2 & 6.2.3, and Section 7.3.1: PK collection timpoints: 96 hours post dose is added for all subjects as it will provide additional information on the PK profile. 48 hour post dose is deleted for subjects who are 12 years old since the 48 hour and 50 hour are very close to each other and the concentrations observed in other trials at these two times are quite similar to each other. Section 6.2.2: The languages regarding the collection time of PK FIX activity samples relevant to infusion are revised from completion of the infusion to start of the infusion as the drug enters the blood at the start of the infusion, thus time ‘zero’ is the start of the infusion. Exclusion criterion #24, and Section 4.4.4: Contraception are deleted as there is no label restriction requiring contraception in males taking Benefix. Section 1.3.1: a statement regarding no contraception requirement on male subjects is added. Exclusion criteria 10, 11, 12 is combined as one criterion and standard language is added. Schedule of activities, Section 3.1 & Section 6.2.1: The requirement on stay in CRU is revised from completion of DAY4/early termination visit activities to completion of the 24 hours post dose PK sample collections, after that, it will be at investigator’s discretion on whether the subjects should stay in CRU or not. The visits that follow hour 24 could be conducted outpatient at investigator’s discretion. For Pediatric subjects, their parents/legal representatives will accompany them during the study if applicable. K–value is replaced by incremental recovery throughout the protocol as K–value is a past used term for incremental recovery and should not continue to be used. Updated Blood Volume table for subjects 6 <12 years old from 55.1 mL to 57.8 mL. Section 6.1.1: height is added to Demography. Section 7.3.3.: FIX inhibitor analysis is added. Pfizer protocol standard language update. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
