Clinical Trial Results:
Routine Prophylaxis Treatment Versus On-demand Treatment for Children With Severe Hemophilia A: Comparison of All Bleeding Events in Chinese Hemophilia Patients
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Summary
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EudraCT number |
2014-001362-10 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
03 Jan 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
07 Sep 2016
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First version publication date |
04 Apr 2015
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Other versions |
v1 |
Version creation reason |
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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 |
BAY14-2222/16287
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01810666 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368
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Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.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 Mar 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Jan 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jan 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study is to evaluate the effect of three times a week prophylaxis on all bleeds compared to on-demand treatment in Chinese children with severe hemophilia A.
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization (ICH) guideline E6: Good Clinical Practice (GCP).
An informed consent form explaining the procedures of the study including the potential hazards was reviewed and approved by the IEC/IRB before its use. Before entering the study, the informed assent/consent form was read by and explained to all subjects or their legally authorized representative. Each subject/ legally authorized representative had ample opportunity to ask questions and was assured of the right to withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision.
Only after the legal representatives of subjects voluntarily signed the informed consent form and the subject voluntary signed the informed assent form, if adequate, was he able to enter the study. If the subject was not capable of providing a signature, an oral statement of consent could have been given in the presence of a witness. Each subject or representative received a signed and dated copy of the informed assent/ consent form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Mar 2013
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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: 30
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Worldwide total number of subjects |
30
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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) |
14
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Adolescents (12-17 years) |
16
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Adults (18-64 years) |
0
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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 |
Subject recruitment period was between 20-Mar-2013 to 28-Jun-2013. | ||||||
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Pre-assignment
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Screening details |
Of 33 participants who were screened for inclusion in the study, 30 were enrolled and received treatment. | ||||||
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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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Rec. factor VIII on-demand followed by prophylaxis | ||||||
Arm description |
Participants received Recombinant Factor VIII (Rec. factor VIII) on-demand treatment for 12 weeks followed by a 12 weeks prophylaxis treatment phase. The dose and mode of prophylaxis treatment was 25 IU/Kg, 3 times/per week. The dose in on-demand treatment was decided by physician according to the package insert or the current standard of care. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Recombinant Factor VIII (Kogenate FS, BAY14-2222)
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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 in pre-filled syringe
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received on-demand treatment for 12 weeks followed by a 12 weeks prophylaxis treatment phase. The dose and mode of prophylaxis treatment was 25 IU/Kg, 3 times/per week. The dose in ondemand treatment was decided by physician according to the package insert or the current standard of care.
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rec. factor VIII on-demand followed by prophylaxis
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Reporting group description |
Participants received Recombinant Factor VIII (Rec. factor VIII) on-demand treatment for 12 weeks followed by a 12 weeks prophylaxis treatment phase. The dose and mode of prophylaxis treatment was 25 IU/Kg, 3 times/per week. The dose in on-demand treatment was decided by physician according to the package insert or the current standard of care. | ||
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End point title |
Difference of annualized number of all bleeds between on-demand and prophylaxis period [1] | ||||||||
End point description |
Annualized bleedings period 1 minus period 2 ITT analysis set.
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End point type |
Primary
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End point timeframe |
Week 1-12 (on-demand treatment) and 13-24 (prophylactic treatment)
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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: 2-sided Hodges Lehmann estimates for median 95% CI Annualized bleedings period 1 minus period 2 ITT analysis set. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Difference of annualized number of joint bleeds between on-demand and prophylaxis period | ||||||||
End point description |
Annualized joint bleedings period 1 minus period 2 ITT analysis set.
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End point type |
Secondary
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End point timeframe |
Week 1-12 (on-demand treatment) and 13-24 (prophylactic treatment)
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| No statistical analyses for this end point | |||||||||
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End point title |
Difference of intra-individual change of joint function during each period assessed by the Hemophilia Joint Health Score between on-demand and prophylaxis period | ||||||||
End point description |
Hemophilia Joint Health Score(HJHS) ranges from 0 to 124. Higher values in the HJHS represent worse situation for the subject. 2-sided Hodges Lehmann estimates for median 95% CI HJHS values difference of changes ITT analysis set.
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End point type |
Secondary
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End point timeframe |
From baseline to Week 12 (on-demand treatment) and Week 24 (prophylactic treatment)
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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 first treatment through 3 days after the last dose of study drug, up to 6 months
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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 |
16.1
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Reporting groups
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Reporting group title |
Recombinant Factor VIII (Kogenate FS, BAY14-2222)
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Reporting group description |
- | ||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Jul 2012 |
Protocol amendment 01, dated 30 JUL 2012
The study design was re- evaluated and several key changes were made to the original protocol, including updates on secondary objectives, population selection criteria, and updates on study procedures. |
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08 Mar 2013 |
Protocol amendment 02, dated 08 MAR 2013
The evaluation of joint function by Physical examination score was excluded via this amendment.
According to the original protocol, joint function was to be evaluated by Hemophilia Joint Health Score (HJHS) (for subjects ≥ 4 years) or Physical examination score (if age of the children < 4 years) as used in JOS. However, Physical examination score was not a well validated evaluation tool, and it was confirmed that HJHS could be applied to children under 4 years old. Therefore only HJHS was to be used to evaluate joint function for all subjects in this study.
In order to minimize the risk of joint bleeding, injection of Kogenate® FS could be administered before the joint evaluation at the discretion of the investigator as per this protocol amendment. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
