Clinical Trial Results:
A Phase III Study on the Safety, Pharmacokinetics and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Patients with Inhibitors to Factor VIII or IX
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Summary
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EudraCT number |
2013-004779-11 |
Trial protocol |
GB BG RO PL |
Global end of trial date |
31 Jul 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jul 2016
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First version publication date |
29 Jul 2016
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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 |
RB-FVIIa-006-13
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02020369 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
LFB USA, Inc.
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Sponsor organisation address |
175 Crossing Blvd, Framingham, United States, 01702
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Public contact |
Jeffry Lawrence, MD, LFB USA, 1 508 370 5113, jeffry.lawrence@lfb-usa.com
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Scientific contact |
Jeffry Lawrence, MD, LFB USA, 1 508 370 5113, jeffry.lawrence@lfb-usa.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-001203-PIP02-14 | ||
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 |
01 Mar 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2015
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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 assess the efficacy of 2 separate dose regimens (75 µg/kg and 225 µg/kg) of LR769 for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to factor VIII or IX.
To assess the safety of LR769. This included the immunogenic potential of the drug product.
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Protection of trial subjects |
Safety was assessed by physical examinations, vital signs, electrocardiograms (ECGs), clinical laboratory tests, immunogenicity testing, and assessment of AEs.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Apr 2014
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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 |
Poland: 1
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
Bulgaria: 2
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Country: Number of subjects enrolled |
United States: 4
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Country: Number of subjects enrolled |
Georgia: 2
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Country: Number of subjects enrolled |
Russian Federation: 5
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Country: Number of subjects enrolled |
Ukraine: 12
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Worldwide total number of subjects |
27
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EEA total number of subjects |
4
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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) |
0
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Adolescents (12-17 years) |
5
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Adults (18-64 years) |
22
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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 |
The study was initiated on 29 April 2014 (first patient, date of first assessment). The study was completed on 31 July 2015 (last patient, last date recorded). 27 patients experienced a total of 468 bleeding episodes (465 mild/moderate and 3 severe bleeding episodes) that were treated with LR769. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
29 patients were screened and 2 of these patients screen failed. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Coagulation Factor VIIa (Recombinant): 75 µg/kg | ||||||||||||||||||||||||
Arm description |
Coagulation Factor VIIa (Recombinant): 75 µg/kg for 3 months Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Coagulation Factor VIIa (Recombinant)
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Investigational medicinal product code |
LR769
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
2-minute IV push of 75 µg/kg every 3 hours as needed for mild/moderate bleeding episodes. Up to 8 administrations within a 24 hour period.
2-minute IV push of 75 µg/kg every 2 hours as needed for Severe bleeding episodes.
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Arm title
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Coagulation Factor VIIa (Recombinant): 225 µg/kg | ||||||||||||||||||||||||
Arm description |
Coagulation Factor VIIa (Recombinant) : 225 µg/kg for 3 months Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Coagulation Factor VIIa (Recombinant)
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Investigational medicinal product code |
LR769
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
2-minute IV push of 225 µg/kg needed for mild/moderate bleeding episodes.
followed 9 hours later with a 2 minute IV infusion of 75 µg/kg of LR769 if needed.
Up to 6 administrations within a 24 hour period.
2-minute IV push of 225 µg/kg for Severe bleeding episodes.
This first dose may have been followed 6 hours later with a 2 minute IV infusion of 75 µg/kg of LR769.
This may have been repeated, if needed, every 2 hours until improvement of the bleeding episode was observed.
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Baseline characteristics reporting groups
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Reporting group title |
Coagulation Factor VIIa (Recombinant): 75 µg/kg
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Reporting group description |
Coagulation Factor VIIa (Recombinant): 75 µg/kg for 3 months Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Coagulation Factor VIIa (Recombinant): 225 µg/kg
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Reporting group description |
Coagulation Factor VIIa (Recombinant) : 225 µg/kg for 3 months Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX | ||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Treated bleeding episodes at 75 µg/kg
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
25 patients analysed in this set ( dose 75 µg/kg)
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Subject analysis set title |
Treated bleeding episode at 225 µg/kg
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
25 patients analysed in this set (dose 225 µg/kg)
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End points reporting groups
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Reporting group title |
Coagulation Factor VIIa (Recombinant): 75 µg/kg
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Reporting group description |
Coagulation Factor VIIa (Recombinant): 75 µg/kg for 3 months Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX | ||
Reporting group title |
Coagulation Factor VIIa (Recombinant): 225 µg/kg
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Reporting group description |
Coagulation Factor VIIa (Recombinant) : 225 µg/kg for 3 months Coagulation Factor VIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75µg/kg and 225 µg/kg) of Coagulation Factor VIIa (Recombinant) for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors to Factor VIII/IX | ||
Subject analysis set title |
Treated bleeding episodes at 75 µg/kg
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
25 patients analysed in this set ( dose 75 µg/kg)
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Subject analysis set title |
Treated bleeding episode at 225 µg/kg
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
25 patients analysed in this set (dose 225 µg/kg)
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End point title |
percentage of successfully treated mild/moderate bleeding episodes [1] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The pre-specified primary efficacy endpoint was the proportion of successfully treated mild/moderate bleeding episodes at 12 hours (bleeding episode level) after initial administration of study drug .
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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: The primary efficacy analysis was performed based on data-as-observed approach. Descriptive analyse. |
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| Notes [2] - 252 Treated (Mild/Moderate) Bleeding Episodes at 12 Hours After Initial Administration of Study Drug [3] - 213 Treated (Mild/Moderate) Bleeding Episodes at 12 Hours After Initial Administration of Study Drug |
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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 |
April 29, 2014 through July 31, 2015
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||
Dictionary version |
15.1
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Reporting groups
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Reporting group title |
Overall patients
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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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07 Feb 2014 |
Added a 3 week visit to the protocol. |
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27 Mar 2014 |
This amendment included the following key changes:
• Upon request of several European countries an immunogenicity sample was added for each 6-week period after the initial 3- and 6-week visits. Several minor corrections were also made.
• Correction of a discrepancy in the number of bleeding episodes and number of patients that determined the study duration.
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31 Jul 2014 |
Amendment contained the following changes to the study:
• Investigational product produced at a larger manufacturing scale was introduced.
• Changes throughout the protocol related to the addition of a repeat PK analysis with Process B study drug.
• Change to procedures at follow-up visits in Phase B to allow some follow-up visits during Phase B to be conducted outside the hospital/hemophilia care center by qualified staff or qualified healthcare professionals. |
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23 Apr 2015 |
Amendment contained the following changes to the protocol:
• Change in the medical monitor, his title and contact information.
• Deletion of the requirement in the synopsis for 10 severe bleeding episodes to have occurred before the end of the study. The rationale for this change was as follows:
-Considering the low incidence of severe bleeding episodes during the study and the absence of any specific regulatory requirement for a certain number of severe bleeding episodes, the text requiring 10 severe bleeding episodes has been deleted. The low incidence of severe bleeding episodes in the patients treated to date reflects the actual incidence of severe bleeding episodes in this population. The company’s intent was to treat a full range of bleeding episodes (from mild to severe), which had been accomplished.
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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 | |||
