Clinical Trial Results:
An Evaluation of the Safety and Efficacy of On-Demand Treatment with BeneFIX (Nonacog Alfa, Recombinant Factor IX) in Chinese Subjects
with Hemophilia B
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Summary
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EudraCT number |
2014-004156-65 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
24 Dec 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
16 May 2016
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First version publication date |
01 Aug 2015
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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 |
3090A1-3305
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00866606 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
alias: B1821004 | ||
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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, NY 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 |
19 Sep 2010
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Dec 2009
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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 |
To describe the safety and clinical efficacy of BeneFIX in previously treated 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 |
18 Sep 2008
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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: 35
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Worldwide total number of subjects |
35
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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) |
6
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Adults (18-64 years) |
25
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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 |
Subjects were enrolled in six centers in China. | ||||||||||||
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Pre-assignment
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Screening details |
Study was initiated on 18 September 2008 and completed on 24 December 2009. A total of 35 subjects were enrolled in the study. | ||||||||||||
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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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BeneFactor IX (BeneFIX) | ||||||||||||
Arm description |
Subjects received on-demand treatments with BeneFIX according to investigator’s prescription over a 6-month (calendar day) period. All BeneFIX administrations occurred in the clinic (hospital). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
BeneFIX
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Investigational medicinal product code |
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Other name |
Nonacog Alfa, Recombinant Factor IX
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
A single 75 International Unit (IU)/kilogram (kg) (±5 IU/kg) intravenous (IV) bolus infusion of BeneFIX was given for recovery assessments.
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Baseline characteristics reporting groups
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Reporting group title |
BeneFactor IX (BeneFIX)
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Reporting group description |
Subjects received on-demand treatments with BeneFIX according to investigator’s prescription over a 6-month (calendar day) period. All BeneFIX administrations occurred in the clinic (hospital). | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BeneFactor IX (BeneFIX)
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Reporting group description |
Subjects received on-demand treatments with BeneFIX according to investigator’s prescription over a 6-month (calendar day) period. All BeneFIX administrations occurred in the clinic (hospital). | ||
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End point title |
Investigator Hemostatic Efficacy Assessment of Subjects After 8 Hours Post Infusion [1] | ||||||||
End point description |
Investigator Hemostatic Efficacy Assessment was based on response of bleeding episodes to BeneFIX treatment on 4-point rating scale: Excellent(1): definite pain relief or improvement in signs of bleeding starting within 8 hours after infusion, with no additional infusion; Good(2): definite pain relief or improvement in signs of bleeding starting within 8 hrs or following infusion; Moderate(3): probable or slight improvement starting after 8 hours following infusion; No Response(4): no improvement at all between infusions or during 24 hour interval following an infusion, or condition worsens. Full Analysis set (FAS) population included all subjects who were treated and had at least 1 evaluable efficacy assessment after treatment.
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End point type |
Primary
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End point timeframe |
8 hours post infusion.
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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: Only descriptive analysis was planned to be reported for this end point. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Investigator Hemostatic Efficacy Assessment of Subjects After 24 Hours Post Infusion [2] | ||||||||
End point description |
Investigator Hemostatic Efficacy Assessment was based on response of bleeding episodes to BeneFIX treatment on 4-point rating scale: Excellent(1): definite pain relief or improvement in signs of bleeding starting within 8 hours after infusion, with no additional infusion; Good(2): definite pain relief or improvement in signs of bleeding starting within 8 hrs or following infusion; Moderate(3): probable or slight improvement starting after 8 hours following infusion; No Response(4): no improvement at all between infusions or during 24 hour interval following an infusion, or condition worsens. FAS population included all subjects who were treated and had at least 1 evaluable efficacy assessment after treatment.
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End point type |
Primary
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End point timeframe |
24 hours post infusion
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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: Only descriptive analysis was planned to be reported for this end point. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With FIX Inhibitor Development [3] | ||||||||||||||
End point description |
Incidence of FIX inhibitor was defined as any result determined as positive at local laboratory, and confirmed at central laboratory with Nijmegen assay result greater than or equal to (>=)0.6 Bethesda Unit (BU). Incidence was stratified by subject exposure history - Minimally Treated Patients (MTPs): those who had received at least one prior FIX infusion, and less than or equal to (<=) 100 documented Exposure Days (EDs); while Previously Treated Patients (PTPs): those who had received >100 documented prior EDs. When number of prior EDs for an individual was not known to be at least 100, subjects were included in the MTP population. Safety Set (SS) population included all enrolled subjects who had taken at least 1 dose of drug. The 'n' is signifying those subjects who received study drug and were evaluated for this measure at the timepoint for each visit respectively.
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End point type |
Primary
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End point timeframe |
Baseline up to 6 months
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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: Only descriptive analysis was planned to be reported for this end point. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of Infusions Required to Treat Each Bleed | ||||||||
End point description |
The number of BeneFIX infusions required to treat each bleeding episode were analyzed. The average frequency of BeneFIX infusions per hemorrhage incidence to treat every hemorrhage was equal to the total number of injections throughout the study divided by total number of hemorrhagic events. FAS population included all subjects who were treated and had at least 1 evaluable efficacy assessment after treatment.
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End point type |
Secondary
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End point timeframe |
Baseline up to 6 months
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| No statistical analyses for this end point | |||||||||
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End point title |
FIX Incremental Recovery | ||||||||||||
End point description |
FIX recovery was assessed by evaluating FIX:C after initial exposure and following 6 months of repeated exposures to BeneFIX. A modified FIX recovery study was performed at Day 1 (Visit 2) and Month 6/Final/Early Termination visits (Visit 4) and when clinically indicated at the applicable on-demand visits. Blood samples for determination of FIX:C were collected immediately before BeneFIX infusion and at 30 minutes (±5 minutes) after the start of infusion. Post-infusion blood samples were collected via venipuncture in arm contralateral to arm used for infusion. FAS population included all subjects who were treated and had at least 1 evaluable efficacy assessment after treatment. The 'n' is signifying those subjects who received study drug and were evaluated for this measure at the timepoint for each visit respectively.
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End point type |
Secondary
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End point timeframe |
Baseline (Visit 2) up to 6 months (Visit 4)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects With Less Than Expected Therapeutic Effect (LETE) | ||||||||
End point description |
The incidence of LETE for on-demand treatment was defined as no response after each of 2 successive infusions within 24 hours for the same bleeding event in the absence of confounding factors. FAS population included all subjects who were treated and had at least 1 evaluable efficacy assessment after treatment.
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End point type |
Secondary
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End point timeframe |
Baseline up to 6 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Allergic-Type Allergic Reactions | ||||||||
End point description |
Hypersensitivity to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. SS population included all enrolled subjects who had taken at least 1 dose of drug.
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End point type |
Secondary
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End point timeframe |
Baseline up to 6 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Thrombosis | ||||||||
End point description |
Thrombosis is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss. SS population included all enrolled subjects who had taken at least 1 dose of drug.
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End point type |
Secondary
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End point timeframe |
Baseline up to 6 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Red Blood Cell (RBC) Agglutination | ||||||||
End point description |
RBC Agglutination is the clumping of red blood cells in the presence of an antibody. The antibody or other molecule bonded multiple particles and joined them, creating a large complex. SS population included all enrolled subjects who had taken at least 1 dose of drug.
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End point type |
Secondary
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End point timeframe |
Baseline up to 6 months
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From screening until 30 days after the last visit (Month 6/Final/Early Termination visit)
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Adverse event reporting additional description |
The same event may appear as both an adverse event (AE) and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
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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 |
BeneFactor IX (BeneFIX)
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Reporting group description |
Subjects received on-demand treatments with BeneFIX according to investigator’s prescription over a 6-month (calendar day) period. A single 75 IU/kg (±5 IU/kg) IV bolus infusion of BeneFIX was given for recovery assessments. All BeneFIX administrations occurred in the clinic (hospital). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
