Clinical Trial Results:
BAX326 (recombinant Factor IX): Evaluation of Safety, Immunogenicity, and Hemostatic Efficacy in Previously Treated Patients with Severe (FIX level < 1%) or Moderately Severe (FIX level 1-2 %) Hemophilia B - A Continuation Study
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Summary
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EudraCT number |
2010-022726-33 |
Trial protocol |
BG CZ GB DE SE PL ES IT IE |
Global end of trial date |
29 Jun 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Jan 2018
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First version publication date |
05 Jan 2018
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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 |
251001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01286779 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Baxalta, now part of Shire
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Sponsor organisation address |
Industriestrasse 67, Vienna, Austria, 1221
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Public contact |
Study Physician, Baxalta, now part of Shire, ClinicalTransparency@shire.com
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Scientific contact |
Study Physician, Baxalta, now part of Shire, ClinicalTransparency@shire.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001139-PIP01-11 | ||
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 |
29 Jun 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Jun 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jun 2017
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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 |
Further evaluate safety of BAX326 in terms of IP-related AEs as well as clinically significant changes in routine laboratory parameters and vital signs. Further evaluate the hemostatic efficacy of BAX326 in the prevention and routine prophylaxis of acute bleeding episodes using various dose regimens. Further evaluate the hemostatic efficacy of BAX326 in the management of acute bleeding episodes. Further evaluate the immunogenicity of BAX326 for up to 100 exposure days to BAX326. Monitor IR of BAX326 over time. Evaluate changes in health related quality of life (HR QoL), patient activity level and health resource use.
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Protection of trial subjects |
This study was conducted in accordance with the study protocol, the International Conference on Harmonisation Guideline for Good Clinical Practice E6 (ICH GCP, April 1996), Title 21 of the US Code of Federal Regulations (US CFR), the European Clinical Trial Directive (2001/20/EC and 2005/28/EC), and applicable national and local regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Apr 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Bulgaria: 10
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Country: Number of subjects enrolled |
Czech Republic: 2
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Country: Number of subjects enrolled |
Ireland: 2
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Country: Number of subjects enrolled |
Italy: 4
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Country: Number of subjects enrolled |
Poland: 22
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Country: Number of subjects enrolled |
Romania: 12
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Country: Number of subjects enrolled |
Sweden: 1
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
India: 1
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Country: Number of subjects enrolled |
Japan: 3
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
Taiwan: 6
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Country: Number of subjects enrolled |
Argentina: 2
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Country: Number of subjects enrolled |
Brazil: 1
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Country: Number of subjects enrolled |
Chile: 5
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Country: Number of subjects enrolled |
Colombia: 4
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Country: Number of subjects enrolled |
Russian Federation: 18
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Country: Number of subjects enrolled |
Ukraine: 21
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Worldwide total number of subjects |
117
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EEA total number of subjects |
55
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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) |
21
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Adolescents (12-17 years) |
5
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Adults (18-64 years) |
89
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Enrollment was conducted at 40 clinical sites in 18 countries. A total of 117 participants were enrolled. Of these, 65 participants transitioned from BAX326 pivotal study, 20 participants transitioned from BAX326 pediatric study and 32 participant were newly recruited. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Of 117 enrolled participants, 115 received treatment with IP. All 85 participants who transitioned from the pivotal/pediatric studies continued to receive IP in this study. Of the 32 newly recruited participants, 30 received treatment with IP. 1 participant did not meet the entry criteria and 1 participant discontinued the study prior treatment. | ||||||||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
117 | ||||||||||||||||||||
Number of subjects completed |
115 | ||||||||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Subject discontinued the study prior treatment: 1 | ||||||||||||||||||||
Reason: Number of subjects |
Screen failure: 1 | ||||||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Overall study | ||||||||||||||||||||
Arm description |
Participants treated with BAX 326 | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Rixubis
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Investigational medicinal product code |
BAX 326
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Treatment with BAX326 is at the discretion of the investigator and consists of either prophylaxis or on-demand. Newly recruited subjects receive prophylactic treatment only. Standard Prophylaxis with twice weekly infusions of 50 IU/kg (range 40-60 IU/kg) which may be increased to 75 IU/kg in subjects ≥12 years of age; range 40-80 IU/kg in subjects <12 years of age. Modified Prophylaxis is determined by the investigator and dose can be increased up to 100 IU/kg, if applicable. PK-tailored Prophylaxis is based on subject's individual PK. The maximum dose is 120 IU/kg.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Of 117 enrolled participants (who signed informed consent), 115 received treatment with investigational product. 1 participant did not meet the entry criteria and 1 participant discontinued the study prior treatment. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
Participants treated with BAX 326 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Comprises all participants who are exposed to any amount of investigational product.
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Subject analysis set title |
Standard prophylaxis
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg
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Subject analysis set title |
Modified prophylaxis
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.
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Subject analysis set title |
PK-tailored prophylaxis
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants treated with BAX 326 with PK tailored prophylaxis based on participant's individual PK with maximum dose of 120 IU/kg.
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Subject analysis set title |
Overall prophylaxis
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)
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Subject analysis set title |
On-demand
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All participants who received BAX 326 as on-demand regimen.
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Subject analysis set title |
Pharmacokinetic full analysis set
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Comprises all participants from the full analysis set who underwent an abbreviated PK study.
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End points reporting groups
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Reporting group title |
Overall study
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Reporting group description |
Participants treated with BAX 326 | ||
Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Comprises all participants who are exposed to any amount of investigational product.
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Subject analysis set title |
Standard prophylaxis
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants treated with BAX 326 with twice weekly prophylactic infusions of 50 IU/kg
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Subject analysis set title |
Modified prophylaxis
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants treated with BAX 326 with prophylactic treatment determined by the investigator. The dose could be increased up to 100 IU/kg if indicated.
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Subject analysis set title |
PK-tailored prophylaxis
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants treated with BAX 326 with PK tailored prophylaxis based on participant's individual PK with maximum dose of 120 IU/kg.
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Subject analysis set title |
Overall prophylaxis
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All participants who received BAX 326 as prophylactic regimen (standard prophylaxis, modified prophylaxis and PK-tailored prophylaxis)
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Subject analysis set title |
On-demand
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All participants who received BAX 326 as on-demand regimen.
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Subject analysis set title |
Pharmacokinetic full analysis set
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Comprises all participants from the full analysis set who underwent an abbreviated PK study.
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End point title |
Adverse events possibly or probably related to the investigational product [1] | ||||||||
End point description |
Possibly or probably related adverse events that occurred during or after first BAX326 infusion.
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End point type |
Primary
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End point timeframe |
Assessed (based on patient diary) every 3 months until study completion.
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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: Per protocol, only descriptive statistics were collected for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Treatment of bleeding episodes: Number of infusions per bleeding episode | |||||||||||||||||||||||||||||||||||
End point description |
Infusions of BAX326 that were required until bleed resolution.
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End point type |
Secondary
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End point timeframe |
Throughout the study from screening to study completion
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Treatment of bleeding episodes: Overall hemostatic efficacy rating at resolution of bleed | |||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusion would not affect the scoring. Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion. Required more than 1 infusion for complete resolution. None: No improvement or condition worsens.
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End point type |
Secondary
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End point timeframe |
Throughout the study from screening to study completion.
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Annualized bleed rate during prophylaxis treatment | ||||||||||||||||||||
End point description |
Annualized bleed rate (ABR) was calculated as (number of bleeding episodes / observed treatment period in days) * 365.25. The ABR was calculated for participants with an observation period of at least 3 months with BAX326 on the specified treatment regimen.
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End point type |
Secondary
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End point timeframe |
For Prophylactic treatment the period from first to last prophylactic infusion is considered.
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Consumption of BAX 326: Number of infusions per month and per year | ||||||||||||||||||||||||||||||||||||
End point description |
The number of infusions consumed per month and per year for the prophylactic and on-demand treatment regimens.
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End point type |
Secondary
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End point timeframe |
Throughout the study from screening to study completion.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Consumption of BAX 326: Weight adjusted consumption per month and per year | ||||||||||||||||||||||||||||||||||||
End point description |
The weight adjusted consumption of BAX 326 per month and per year for the prophylactic and on-demand treatment regimens.
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End point type |
Secondary
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End point timeframe |
Throughout the study from screening to study completion.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Consumption of BAX326: Weight adjusted consumption per bleeding episode | ||||||||||||||||||||||||||||||
End point description |
The weight adjusted consumption of BAX 326 per bleeding episode for the prophylactic and on-demand treatment regimens. Only infusions required until the resolution of bleed are considered.
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End point type |
Secondary
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End point timeframe |
Throughout the study from screening to study completion.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Development of inhibitory and total binding antibodies to FIX | ||||||||||||
End point description |
Testing for inhibitory and total binding antibodies to FIX. Development during study means negative at screening and positive at any subsequent visit. Treatment emergent means more than 2-dilution increase as compared to the pre-study titer at screening.
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End point type |
Secondary
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End point timeframe |
Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Development of antibodies to Chinese Hamster Ovary Proteins (CHO proteins) and rFurin | ||||||||||||
End point description |
Testing for antibodies to CHO proteins and rFurin. Development during study means negative at screening and positive at any subsequent visit. Treatment emergent means more than 2-dilution increase as compared to the pre-study titer at screening.
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End point type |
Secondary
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End point timeframe |
Laboratory assessment for immunology were done at screening, at exposure day 1, at week 4 (± 1 week), at month 3 (±1 week), thereafter, every 3 months (± 1 week) and at study completion/termination.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Occurrence of severe allergic reactions and thrombotic events | ||||||||||
End point description |
The occurrence of severe allergic reactions and thrombotic events was assessed.
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End point type |
Secondary
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End point timeframe |
Throughout the study from screening to study completion.
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| No statistical analyses for this end point | |||||||||||
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End point title |
Clinical significant changes in routine laboratory parameters and vital signs | ||||||||||||||||
End point description |
Hematology panel consists of complete blood count (hemoglobin, hematocrit, erythrocytes, leukocytes) with differential (ie, basophils, eosinophils, lymphocytes, monocytes, neutrophils), mean corpuscular volume, mean corpuscular hemoglobin concentration and platelet count. Clinical chemistry panel consists of sodium, potassium, chloride, bicarbonate, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase, blood urea nitrogen, creatinine and glucose. Vital signs include body temperature, respiratory rate, pulse rate, supine systolic and diastolic blood pressure.
CS = clinically significant, NCS = not clinically significant
Change from Screening to End of Study is reported.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Measurements at screening and at study completion/termination are included in the analysis.
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||
End point title |
Pharmacokinetics: Incremental Recovery (IR) over time | ||||||||||||||
End point description |
PK infusion with investigational product was administered after a wash out period of at least 5 days. Incremental recovery is calculated as IR30min = (C30min [IU/dL] - Cpre-infusion [IU/dL]) / dose per kg body weight [IU/kg] where C30min and Cpre-infusion relate to the unadjusted concentration values. All subjects treated with investigational product were included in this analysis.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
IR over time was analysed at Baseline and at Completion/Termination visit within 30 minutes pre-infusion and at 30 (± 5) minutes post-infusion.
|
||||||||||||||
|
|||||||||||||||
| Notes [2] - n=110 at baseline, n=108 at end of study, n=104 for change |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||
End point title |
Pharmacokinetics: Area under the plasma concentration versus time curve from time 0 to infinity (AUC 0-∞) | ||||||||||
End point description |
After a wash out period of at least 5 days PK infusion with investigational product was administered. AUC 0-∞ is defined as AUC 0-t + Ct/lambda z, where t is the time of last quantifiable concentration, Ct is the last quantifiable concentration.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 minutes, 9 hours, 24 hours, 48 hours and 72 hours
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
Pharmacokinetics: Elimination phase half-life (T1/2) | ||||||||||
End point description |
PK infusion with investigational product was administered after a wash out period of at least 5 days. Elimination phase half-life is calculated as T1/2=log e (2) / lambda z where the elimination rate constant (lambda z) will be obtained by log e - linear fitting using least squares deviation to at least the last 3 quantifiable concentrations above pre-infusion level.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 minutes, 9 hours, 24 hours, 48 hours and 72 hours
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
Pharmacokinetics: Mean residence time (MRT) | ||||||||||
End point description |
PK infusion with investigational product was administered after a wash out period of at least 5 days. Mean residence time is calculated as total area under the moment curve divided by the total area under the curve. MRT=(AUMC0-∞[h2*IU/dL])/(AUC0-∞[h*IU/dL]) - TI/2 where AUMC0-∞ is determined in a similar manner as AUC0-∞ and TI represents infusion duration in hours.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 minutes, 9 hours, 24 hours, 48 hours and 72 hours
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
Pharmacokinetics: Systemic Clearance (CL) | ||||||||||
End point description |
PK infusion with investigational product was administered after a wash out period of at least 5 days. Systemic clearance is calculated as the dose in IU/kg divided by the total AUC. CL= Dose[IU/kg] / AUC0-∞[h*IU/dL]
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 minutes, 9 hours, 24 hours, 48 hours and 72 hours
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
Pharmacokinetics: Volume of distribution at steady state (Vss) | ||||||||||
End point description |
PK infusion with investigational product was administered after a wash out period of at least 5 days. Apparent steady state volume of distribution is calculated as Vss = CL * MRT CL=Systemic Clearance and MRT=Mean residence time
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
PK assessments were done within 30 minutes pre-infusion and post-infusion at 30 minutes, 9 hours, 24 hours, 48 hours and 72 hours
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
End point title |
Pharmacokinetics: Incremental recovery (IR) | ||||||||||
End point description |
PK infusion with investigational product was administered after a wash out period of at least 5 days. Incremental recovery is calculated as IR30min = (C30min [IU/dL] - Cpre-infusion [IU/dL]) / dose per kg body weight [IU/kg] where C30min and Cpre-infusion relate to the unadjusted concentration values.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
IR assessments were done within 30 minutes pre-infusion and post-infusion at 30 (± 5) minutes.
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Changes in health related quality of life (HR QoL) based on questionnaire SF-36 | ||||||||||||||||||||||||||||
End point description |
The SF-36 is a validated, generic HR QoL instrument, measuring physical, emotional, social functioning as well as overall general health, suitable for subjects of 17 years of age or older. Higher scores indicate better health status. The Change in health related quality of life is analyzed from baseline to study completion. Only newly recruited subjects are included in the analysis of change as baseline values were not reported for transitioning subjects. Only subjects who received prophylaxis treatment are included.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Baseline at exposure day 1 and at study completion/termination.
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
|||||||||||||||
End point title |
Changes in health related quality of life using the Peds QL | ||||||||||||||
End point description |
The Peds QL is a generic HR QoL instrument designed specifically for a pediatric population. It captures following domains: general health/activities, feelings/emotional, social functioning, school functioning. Higher scores indicate better quality of life. The Change in health related quality of life is analyzed from baseline to study completion. Only newly recruited subjects are included in the analysis of change as baseline values were not reported for transitioning subjects. Only subjects who received prophylaxis treatment are included.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline at exposure day 1 and at study completion/termination.
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||
End point title |
Changes in health related quality of life (HR QoL) based on questionnaire Haemo-QoL and Haem-A-QoL | ||||||||||||
End point description |
The Haemo-QoL and Haem-A-Qol instruments have been developed and used in hemophilia A patients. As a hemophilia-specific instrument, this measure assesses very specific aspects of dealing with hemophilia. The areas covered by this instrument are: physical health, sports/leisure, school/work, dealing with hemophilia, and outlook for the future. For both instruments higher scores indicate worse quality of life.
The Change in health related quality of life is analyzed from baseline to study completion. Only newly recruited subjects are included in the analysis of change as baseline values were not reported for transitioning subjects. Only subjects who received prophylaxis treatment are included.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline at exposure day 1 and at study completion/termination.
|
||||||||||||
|
|||||||||||||
| Notes [3] - n=16 for Haem-A-QoL and n=1 for Haemo-Qol - Dispersion not applicable as n=1, entered as 99.999 |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||
End point title |
Changes in health related quality of life (HR QoL) based on questionnaire EQ-5D and pain score. | ||||||||||||||
End point description |
The EQ-5D captures overall HR QoL (phyiscal, mental and social functioning). A health utility score can be calculated from this measure, adult and proxy versions available. General pain assessment are done through a visual analog scale (VAS). For the EQ-5D Index score and EQ-5D VAS score, a higher score represents better quality of life. For the pain scale, a higher score indicates worse pain.
The Change in health related quality of life is analyzed from baseline to study completion. Only newly recruited subjects are included in the analysis of change as baseline values were not reported for transitioning subjects. Only subjects who received prophylaxis treatment are included.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline at exposure day 1 and at study completion/termination.
|
||||||||||||||
|
|||||||||||||||
| Notes [4] - n=26 for EQ-5D Total Index, n=25 for EQ-5D VAS, n=24 for Pain Score |
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
Throughout the entire study period from screening to completion/termination. Overall 6 years and 2 months.
|
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
N/A
|
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|
Reporting groups
|
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Reporting group title |
BAX 326
|
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Reporting group description |
Participants treated with BAX 326 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
07 Dec 2011 |
Enrollment opened to pediatric subjects who participated in BAX326 pediatric study 251101 (to enable pediatric subjects to continue to receive BAX326 after completion of the pediatric study ); other changes made due to the inclusion of pediatric subjects:
- 80 IU/kg stated as upper end of dose range for pediatric subjects
- Anticipated IR of 0.7 [IU/dL]/[IU/kg] stated for pediatric subjects for calculation of the required number of units to treat a bleeding episode
- Separate analyses between adult and pediatric subjects, if applicable |
||
31 Jul 2013 |
- Enrollment opened to at least 25 subjects naïve to BAX326 (per regulatory authority request).
- Addition of PK-tailored prophylactic administration of BAX326 as an additional prophylactic treatment option.
- Clarification provided that newly recruited subjects had to receive prophylactic treatment.
- IR for calculating dose for subjects ≥ 12 years of age updated from 0.8 to 0.9 (based on PK data of BAX326 pivotal protocol 250901) -> Formula changed to: ‘body weight (kg) x desired FIX rise (% or (IU/dL)) x 1.1 IU/kg’ (previously 1.3 IU/kg)
- Addition of TGA testing for the following new exploratory objective: “To correlate pre-infusion TGA parameters with pre-infusion FIX levels and spontaneous breakthrough bleeds in a subset of subjects receiving twice weekly standard or modified prophylactic treatment, including PK-tailored prophylaxis” (to evaluate whether and which TGA parameters, in particular endogenous thrombin potential (ETP) and/or peak thrombin generation may be a better parameter to monitor the adequacy of prophylactic treatment instead of FIX activity trough levels and/or clinical outcome); TGA testing was only to be performed in subjects ≥ 12 years of age |
||
19 Oct 2015 |
- Term “Cohort 1” introduced for subjects who were previously treated in BAX326 Studies 250901 or 251101; term “Cohort 2” introduced for newly recruited, BAX326 naïve subjects
- Maximum dose of 120 IU/kg introduced for PK-tailored prophylaxis |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
