Clinical Trial Results:
An Evaluation of the Safety and Efficacy of On-Demand Treatment with Xyntha (B-Domain Deleted Recombinant Factor VIII, Albumin Free) in Chinese Subjects with Hemophilia A
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Summary
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EudraCT number |
2014-004106-15 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
04 Dec 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Jun 2016
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First version publication date |
09 Jul 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 |
3082B2-3316
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00868530 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Alias: B1831015 | ||
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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 |
27 Jun 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 |
04 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 Xyntha in previously treated Chinese subjects with hemophilia A.
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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 |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
1 Months | ||
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 |
China: 53
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Worldwide total number of subjects |
53
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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) |
6
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Adolescents (12-17 years) |
11
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Adults (18-64 years) |
36
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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 recruited in China from September 2008 to December 2009. | ||||||||||||
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Pre-assignment
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Screening details |
Overall, 55 subjects were screened, out of which 53 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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Xyntha | ||||||||||||
Arm description |
Subjects received on-demand treatments with Xyntha (which occurred each time a subject experienced bleeding episode during the active phase of the study) according to investigator’s prescription over a 6-month (calendar day) period. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Xyntha
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for injection/infusion
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
A single 50 International Unit (IU)/kg (+/-5 IU/kg) intravenous (IV) bolus infusion of Xyntha was given for recovery assessments.
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Baseline characteristics reporting groups
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Reporting group title |
Xyntha
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Reporting group description |
Subjects received on-demand treatments with Xyntha (which occurred each time a subject experienced bleeding episode during the active phase of the study) according to investigator’s prescription over a 6-month (calendar day) period. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Xyntha
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Reporting group description |
Subjects received on-demand treatments with Xyntha (which occurred each time a subject experienced bleeding episode during the active phase of the study) according to investigator’s prescription over a 6-month (calendar day) period. | ||
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End point title |
Investigator Hemostatic Efficacy Assessment 8 Hours Post Infusion [1] | ||||||||
End point description |
The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions). The Full Analysis Set (FAS) consisted of 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 data 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 24 Hours Post Infusion [2] | ||||||||
End point description |
The Investigator Hemostatic Efficacy Assessment was based on a 4-point rating scale (Excellent = 1: definite pain relief or improvement in signs of bleeding, with no additional infusion, Good = 2: definite pain relief or improvement in signs of bleeding, Moderate = 3: probable or slight improvement, No Response = 4: no improvement at all between infusions). The FAS consisted of 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 data 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 Subjects With Factor VIII (FVIII) Inhibitor Development [3] | ||||||||||
End point description |
Incidence of FVIII inhibitor was defined as any result determined as positive at local laboratory, and confirmed at central laboratory. Incidence was stratified by subject exposure history: Minimally Treated Patients (MTPs): those who had received at least 1 prior FVIII infusion, and less than or equal to (<=) 100 documented Exposure Days (EDs), while Previously Treated Patients (PTPs): those who had received greater than (>) 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. The FAS consisted of 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 |
Day 1 and Month 6 or Early Termination Visit
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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 data 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 |
FVIII Recovery : Change From Baseline in FVIII Concentration [4] | ||||||||
End point description |
FVIII recovery was assessed by evaluating the change in FVIII concentration at 6 months compared to baseline. The FAS consisted of all subjects who were treated and had at least 1 evaluable efficacy assessment after treatment. Subjects with missing data were not included.
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End point type |
Primary
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End point timeframe |
Day 1 and Month 6 or Early Termination Visit
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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: Statistical analysis has been provided separately as an attachment. |
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Attachments |
Statistical Analyses for FVIII Recovery |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects With Less Than Expected Therapeutic Effect (LETE) | ||||||
End point description |
The incidence of LETE, defined for on-demand treatment as no response after each of 2 successive infusions within 24 hours for the same bleeding event in the absence of confounding factors. The FAS consisted of 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 |
24 hours after each of 2 successive infusion, up to 6 months
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Thrombosis Allergic-Type Reactions | ||||||
End point description |
The Safety Set (SS) consisted of all subjects who had taken at least 1 dose of investigational 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 |
Number of Subjects With Thrombosis | ||||||
End point description |
The SS consisted of all subjects who had taken at least 1 dose of investigational 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 |
Frequency of Xyntha Infusions Required Per Hemorrhage | ||||||||
End point description |
The mean frequency of Xyntha infusions per hemorrhage was calculated as total number of injections throughout the study divided by total number of hemorrhagic events. The FAS consisted of all subjects who were treated and had at least 1 evaluable efficacy assessment after treatment.
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End point type |
Other pre-specified
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End point timeframe |
Day 1 to Month 6 or Early Termination Visit
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| No statistical analyses for this end point | |||||||||
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End point title |
Average Dose of Xyntha Infusions Required Per Hemorrhage | ||||||||
End point description |
The average dose of Xyntha per hemorrhagic event was calculated as total dose of Xyntha throughout the study (in IU) divided by total number of hemorrhage incidence. The FAS consisted of all subjects who were treated and had at least 1 evaluable efficacy assessment after treatment.
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End point type |
Other pre-specified
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End point timeframe |
Day 1 to Month 6 or Early Termination Visit
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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 |
Adverse Events (AEs) and Serious AEs (SAEs) were collected from the signing of the informed consent form to approximately 30 days following the Month 6/Final/Early Termination visit
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Adverse event reporting additional description |
Safety population: who received at least 1 dose of Xyntha. Same event may appear as AE, SAE. However,what is presented are distinct events. An event may be categorized as serious in 1 subject and nonserious in another,or 1 subject may experience both SAE, Non-SAE. EU BR AE tables generated separately as per EU format using latest coding dictionary.
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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 |
Xyntha
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Reporting group description |
Subjects received on-demand treatments with Xyntha (which occurred each time a subject experienced bleeding episode during the active phase of the study) according to investigator’s prescription over a 6-month (calendar day) period. A single 50 International Unit (IU)/kg (+/-5 IU/kg) intravenous (IV) bolus infusion of Xyntha was given for recovery assessments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | |||
