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Efficacy and Safety of AlphaNine Versus BeneFIX in Patients With Severe Hereditary Haemophilia B

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ClinicalTrials.gov Identifier: NCT03091751
Recruitment Status : Completed
First Posted : March 27, 2017
Results First Posted : July 25, 2017
Last Update Posted : July 25, 2017
Sponsor:
Information provided by (Responsible Party):
Grifols Biologicals Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemophilia B
Intervention Drug: BeneFIX
Enrollment 13
Recruitment Details  
Pre-assignment Details  
Arm/Group Title BeneFIX
Hide Arm/Group Description

BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

Period Title: Overall Study
Started 22
Completed 22
Not Completed 0
Arm/Group Title BeneFIX
Hide Arm/Group Description

BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

Overall Number of Baseline Participants 22
Hide Baseline Analysis Population Description
Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
<=18 years
1
   4.5%
Between 18 and 65 years
21
  95.5%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Female
0
   0.0%
Male
22
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
22
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine
Hide Description BeneFIX pharmacokinetic parameter of area under the curve (AUC 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 study).
Time Frame Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
Arm/Group Title BeneFIX
Hide Arm/Group Description:

BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: IU x hour/dL
10.41  (563.081)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BeneFIX
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.77
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.41
Confidence Interval (2-Sided) 95%
-224.88 to 245.70
Estimation Comments [Not Specified]
2.Primary Outcome
Title Mean Difference of In Vivo Recovery: BeneFIX Compared to AlphaNine
Hide Description BeneFIX pharmacokinetic parameter of in vivo recovery was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Time Frame Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
Arm/Group Title BeneFIX
Hide Arm/Group Description:

BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: kg/dL
0.3068  (0.37505)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BeneFIX
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3068
Confidence Interval (2-Sided) 95%
0.1501 to 0.4635
Estimation Comments [Not Specified]
3.Primary Outcome
Title Mean Difference of Terminal Half-Life: BeneFIX Compared to AlphaNine
Hide Description BeneFIX pharmacokinetic parameter of terminal half-life was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Time Frame Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
Arm/Group Title BeneFIX
Hide Arm/Group Description:

BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: hours
-3.3  (13.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BeneFIX
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-8.9 to 2.3
Estimation Comments [Not Specified]
4.Primary Outcome
Title Mean Difference of Clearance: BeneFIX Compared to AlphaNine
Hide Description BeneFIX pharmacokinetic parameter of clearance was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Time Frame Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
Arm/Group Title BeneFIX
Hide Arm/Group Description:

BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: mL/min x kg
-0.0058  (0.0145)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BeneFIX
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.0058
Confidence Interval (2-Sided) 95%
-0.0119 to 0.0003
Estimation Comments [Not Specified]
5.Primary Outcome
Title Mean Difference of Mean Residence Time (MRT): BeneFIX Compared to AlphaNine
Hide Description BeneFIX pharmacokinetic parameter of mean residence time (MRT 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Time Frame Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).
Arm/Group Title BeneFIX
Hide Arm/Group Description:

BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

Overall Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: hours
-7.609  (13.7121)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BeneFIX
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -7.609
Confidence Interval (2-Sided) 95%
-13.344 to -1.879
Estimation Comments [Not Specified]
Time Frame Adverse events produced during and after treatment administration were recorded.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title BeneFIX
Hide Arm/Group Description

BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

BeneFIX: BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

All-Cause Mortality
BeneFIX
Affected / at Risk (%)
Total   0/22 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
BeneFIX
Affected / at Risk (%)
Total   0/22 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
BeneFIX
Affected / at Risk (%)
Total   0/22 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Site may publish results from the study, after providing Sponsor 30 days’ notice prior to submitting a manuscript or other materials related to the study to any outside party. At Sponsor’s request, site will remove any confidential information (other than study results) and site will, upon Sponsor’s request, delay publication or presentation for a period of up to 120 days to allow Sponsor to protect its interests in any Sponsor interventions.
Results Point of Contact
Name/Title: Henry Li, PhD
Organization: Grifols Therapeutics Inc
Phone: +1 919 316 6042
Responsible Party: Grifols Biologicals Inc.
ClinicalTrials.gov Identifier: NCT03091751     History of Changes
Other Study ID Numbers: IG-404-1
First Submitted: March 16, 2017
First Posted: March 27, 2017
Results First Submitted: April 13, 2017
Results First Posted: July 25, 2017
Last Update Posted: July 25, 2017