Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III Study on the Safety, Pharmacokinetics, and Efficacy of Coagulation Factor VIIa (Recombinant) in Congenital Hemophilia A or B Pediatric Patients from birth to <12 years old with Inhibitors to Factor VIII or IX: PerSept 2

    Summary
    EudraCT number
    		 2015-000958-38
    Trial protocol
    		 CZ   BG   IT  
    Global end of trial date
    30 Aug 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Feb 2021
    First version publication date
    12 Feb 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LFB-FVIIa-007-14
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02448680
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    LFB USA, Inc.
    Sponsor organisation address
    175 Crossing Boulevard, Framingham, United States, 01702
    Public contact
    Director US Clinical Operations, LFB USA, Inc., 1 5083705166,
    Scientific contact
    Director US Clinical Operations, LFB USA, Inc., 1 5083705166,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001203-PIP02-14
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Sep 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Aug 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of the study is to assess the safety, efficacy and pharmacokinetics of 2 separate dose regimens (75 μg/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 or IX in 13 patients ( birth to <6 years old), and 12 patients (≥6 years old to <12 years old).
    Protection of trial subjects
    This study was conducted in compliance with good clinical practice (GCP) as described in the International Conference on Harmonisation (ICH) document “Guidance for Industry-E6 Good Clinical Practice: Consolidated Guidance” dated April 1996 and its addendum dated November 2016. These practices were consistent with the principles stated in the Declaration of Helsinki (October 2013 revised version). All other applicable regulations were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 This is not an active or placebo-controlled study, as a control arm is not feasible and not ethical.
    Actual start date of recruitment
    07 Dec 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Czech Republic: 1
    Country: Number of subjects enrolled
    Georgia: 2
    Country: Number of subjects enrolled
    Mexico: 3
    Country: Number of subjects enrolled
    South Africa: 6
    Country: Number of subjects enrolled
    United States: 1
    Country: Number of subjects enrolled
    Ukraine: 12
    Worldwide total number of subjects
    25
    EEA total number of subjects
    1
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    5
    Children (2-11 years)
    20
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Enrollment was conducted at a total of 10 sites in 7 countries (USA, Czech Republic, Turkey, Ukraine, South Africa, Mexico and Georgia). Ten sites screened subjects and of these, 8 sites randomized a total of 25 subjects.

    Pre-assignment
    Screening details
    		 31 Subjects were screened. 25 Subjects were enrolled. Screen failure reasons included: Consent Withdrawal (1), Patient ineligible (3), Other (2)

    Period 1
    Period 1 title
    Active Treatment Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    No comparator

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 FVIIa: 75 μg/kg First, Then 225 μg/kg
    Arm description
    		 Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study. A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Coagulation Factor VIIa (recombinant)
    Investigational medicinal product code
    LR769
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Two-minute IV push of 75 µg/kg every 3 hours as needed for mild/moderate bleeding episodes. Up to eight administrations within a 24 hour period. Two-minute IV push of 75 µg/kg every 2 hours as needed for severe bleeding episodes.

    Arm title
    		 FVIIa: 225 μg/kg First, Then 75 μg/kg
    Arm description
    		 Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study. A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Coagulation Factor VIIa (recombinant)
    Investigational medicinal product code
    LR769
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Two-minute IV push of 225 µg/kg for mild/moderate bleeding episodes, followed 9 hours later with a two minute IV infusion of 75 µg/kg of LR769 every 3 hours if needed. Up to 6 administrations within a 24 hour period. Two-minute IV push of 225 µg/kg for severe bleeding episodes. This first dose may have been followed 6 hours later with a two-minute IV infusion of 75 µg/kg of LR769. This may have been repeated, if needed, every two hours until improvement of the bleeding episode was observed.

    Number of subjects in period 1
    		FVIIa: 75 μg/kg First, Then 225 μg/kg FVIIa: 225 μg/kg First, Then 75 μg/kg
    Started
    12
    13
    Completed
    11
    10
    Not completed
    1
    3
         Physician decision
    1
    1
         Consent withdrawn by subject
    -
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    FVIIa: 75 μg/kg First, Then 225 μg/kg
    Reporting group description
    		 Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study. A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX.

    Reporting group title
    FVIIa: 225 μg/kg First, Then 75 μg/kg
    Reporting group description
    		 Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study. A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX.

    Reporting group values
    		 FVIIa: 75 μg/kg First, Then 225 μg/kg FVIIa: 225 μg/kg First, Then 75 μg/kg Total
    Number of subjects
    		 12 13 25
    Age categorical
    Units: Subjects
        Birth to < 6 years old
    		 6 7 13
        >= 6 years to < 12 years old
    		 6 6 12
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 4.9 ± 3.02 4.8 ± 3.63 -
    Gender categorical
    Units: Subjects
        Female
    		 0 0 0
        Male
    		 12 13 25
    Race (MIH/OMB)
    Units: Subjects
        Black or African American
    		 4 3 7
        White
    		 8 10 18
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1 2 3
        Not hispanic or latino
    		 11 11 22
    Weight
    Units: Kg
        arithmetic mean (standard deviation)
    		 19.73 ± 7.432 21.94 ± 13.391 -
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 104.21 ± 21.210 108.60 ± 25.904 -
    Body Mass Index (BMI)
    Units: Kg/m2
        arithmetic mean (standard deviation)
    		 17.74 ± 2.505 17.35 ± 3.842 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    FVIIa: 75 μg/kg First, Then 225 μg/kg
    Reporting group description
    		 Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study. A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX.

    Reporting group title
    FVIIa: 225 μg/kg First, Then 75 μg/kg
    Reporting group description
    		 Coagulation Factor VIIa (Recombinant) : First Intervention (3 months), Second Intervention (3 months), repeat sequence for entirety of study. A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX.

    Subject analysis set title
    Coagulation Factor VIIa (Recombinant): 75 μg/kg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Coagulation Factor VIIa (Recombinant): 75 μg/kg Treatment Regimen at Time of Mild/Moderate Bleeding Episode followed if needed subsequent doses of 75 μg/kg. (75 μg/kg treatment regimen for 3 months) . A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX. This is the Treated Population.

    Subject analysis set title
    Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Coagulation Factor VIIa (Recombinant): 225 μg/kg Treatment Regimen at Time of Mild/Moderate/Severe Bleeding Episode followed if needed subsequent doses of 75 μg/kg. (225 μg/kg treatment regimen for 3 months) . A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX. This is Treated Population.

    Primary: Proportion of Successfully Treated Mild/Moderate Bleeding Per FDA Requirement

    		 Close Top of page
    End point title
    		 Proportion of Successfully Treated Mild/Moderate Bleeding Per FDA Requirement
    End point description
    For the primary efficacy endpoint, successful treatment of mild/moderate bleeding episode was defined as meeting all of the following: • “Good” or “excellent” response noted by the patient/parent/legal guardian or other caregiver, depending on patient’s age and maturity • Study drug treatment: No further treatment with LR769 beyond timepoint where a “good” or “excellent” response for this bleeding episode was noted. • No other hemostatic treatment needed for this bleeding episode • No administration of blood products that would indicate continuation of bleeding beyond timepoint where a “good” or “excellent” response for this bleeding episode was noted • No increase of pain beyond timepoint where a “good” or “excellent” where a “good” or “excellent” response for this bleeding episode was noted that could not be explained other than as continuation of bleeding
    End point type
    Primary
    End point timeframe
    12 hours after first administration of study drug
    End point values
    		 Coagulation Factor VIIa (Recombinant): 75 μg/kg Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects analysed
    23 [1]
    23 [2]
    Units: Proportion of successfully treated BEs
        number (confidence interval 95%)
    0.654 (0.523 to 0.785)
    0.603 (0.482 to 0.723)
    Notes
    [1] - 239 bleeding episodes analyzed
    [2] - 307 Bleeding episodes analyzed
    Statistical analysis title
    		 Comparing prop with an OPC of 0.55 in 75 μg/kg
    Statistical analysis description
    In 75 μg/kg regimen, the null hypothesis (H0) that the true proportion of success (p) ≤0.55 versus Ha that p >0.55 was tested using a 1-sided, 1-sample, normal approximation test and a test statistic obtained by dividing (estimate of p - 0.55) by its estimated SD, taking into account the correlation between BEs for a given patient. The test was conducted at the 0.0125 level (adjusted from 0.025 to 0.0125 to account for multiplicity of testing). OPC = Objective performance criterion
    Comparison groups
    Coagulation Factor VIIa (Recombinant): 75 μg/kg v Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    P-value
    		 = 0.06
    Method
    		 1-sided, 1-sample, normal approximation
    Confidence interval
    Notes
    [3] - The null hypothesis, i.e., comparing the proportion of success with a pre-specified OPC of 0.55, was tested within 75 μg/kg treatment regimen (239 bleeding episodes reported by 23 patients). The results reported (p-value and 95% confidence interval) are not comparing the 2 treatment regimens (i.e., 75 μg/kg and 225 μg/kg regimens).
    Statistical analysis title
    		 Comparing prop with an OPC of 0.55 in 225 μg/kg
    Statistical analysis description
    In 225 μg/kg regimen, the null hypothesis (H0) that the true proportion of success (p) ≤0.55 versus Ha that p >0.55 was tested using a 1-sided, 1-sample, normal approximation test and a test statistic obtained by dividing (estimate of p - 0.55) by its estimated SD, taking into account the correlation between BEs for a given patient. The test was conducted at the 0.0125 level (adjusted from 0.025 to 0.0125 to account for multiplicity of testing). OPC = Objective performance criterion
    Comparison groups
    Coagulation Factor VIIa (Recombinant): 225 μg/kg v Coagulation Factor VIIa (Recombinant): 75 μg/kg
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    P-value
    		 = 0.196
    Method
    		 1-sided, 1-sample, normal approximation
    Confidence interval
    Notes
    [4] - The null hypothesis, i.e.,comparing the proportion of success with a pre-specified OPC of 0.55, was tested within 225 μg/kg treatment regimen (307 bleeding episodes reported by 23 patients). The results reported (p-value and 95% confidence interval) are not comparing the 2 treatment regimens (i.e., 75 μg/kg and 225 μg/kg regimens).

    Primary: Proportion of Successfully Treated Bleeding Episodes (Mild/Moderate/Severe) Per EMA Definition

    		 Close Top of page
    End point title
    		 Proportion of Successfully Treated Bleeding Episodes (Mild/Moderate/Severe) Per EMA Definition
    End point description
    • "Good" or "excellent" response noted by the patient/caregiver for mild/moderate bleeding episodes, • "Good" or "excellent" response noted by the physician for severe bleeding episodes.
    End point type
    Primary
    End point timeframe
    12 hours after first administration of study drug
    End point values
    		 Coagulation Factor VIIa (Recombinant): 75 μg/kg Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects analysed
    23 [5]
    24 [6]
    Units: Proportion success of BEs
        number (confidence interval 95%)
    0.667 (0.533 to 0.800)
    0.625 (0.500 to 0.750)
    Notes
    [5] - 239 bleeding episodes analyzed
    [6] - 310 Bleeding episodes analyzed
    Statistical analysis title
    		 Comparing prop with an OPC of 0.55 in 75 μg/kg
    Statistical analysis description
    In 75 μg/kg regimen, the null hypothesis (H0) that the true proportion of success (p) ≤0.55 versus Ha that p >0.55 was tested using a 1-sided, 1-sample, normal approximation test and a test statistic obtained by dividing (estimate of p - 0.55) by its estimated SD, taking into account the correlation between BEs for a given patient. The test was conducted at the 0.0125 level (adjusted from 0.025 to 0.0125 to account for multiplicity of testing). OPC = Objective performance criterion
    Comparison groups
    Coagulation Factor VIIa (Recombinant): 75 μg/kg v Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    P-value
    		 = 0.043
    Method
    		 1-sided, 1-sample, normal approximation
    Confidence interval
    Notes
    [7] - The null hypothesis, i.e., comparing the proportion of success with a pre-specified OPC of 0.55, was tested within 75 μg/kg treatment regimen (239 bleeding episodes reported by 23 patients). The results reported (p-value and 95% confidence interval) are not comparing the 2 treatment regimens (i.e., 75 μg/kg and 225 μg/kg regimens).
    Statistical analysis title
    		 Comparing prop with an OPC of 0.55 in 225 μg/kg
    Statistical analysis description
    In 225 μg/kg regimen, the null hypothesis (H0) that the true proportion of success (p) ≤0.55 versus Ha that p >0.55 was tested using a 1-sided, 1-sample, normal approximation test and a test statistic obtained by dividing (estimate of p - 0.55) by its estimated SD, taking into account the correlation between BEs for a given patient. The test was conducted at the 0.0125 level (adjusted from 0.025 to 0.0125 to account for multiplicity of testing). OPC = Objective performance criterion
    Comparison groups
    Coagulation Factor VIIa (Recombinant): 225 μg/kg v Coagulation Factor VIIa (Recombinant): 75 μg/kg
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [8]
    P-value
    		 = 0.12
    Method
    		 1-sided, 1-sample, normal approximation
    Confidence interval
    Notes
    [8] - The null hypothesis, i.e.,comparing the proportion of success with a pre-specified OPC of 0.55, was tested within 225 μg/kg treatment regimen (310 bleeding episodes reported by 24 patients). The results reported (p-value and 95% confidence interval) are not comparing the 2 treatment regimens (i.e., 75 μg/kg and 225 μg/kg regimens).

    Secondary: FDA Definition - Patient-Reported "Good" or "Excellent" Response for Mild/Moderate Bleeding Episodes

    		 Close Top of page
    End point title
    		 FDA Definition - Patient-Reported "Good" or "Excellent" Response for Mild/Moderate Bleeding Episodes
    End point description
    Based on Patient-Reported "Good" or "Excellent" responses as per the below descriptions: Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug. Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal hemorrhage). No additional infusion of study drug was required. Statistical analysis : The observed proportion of successfully treated mild/moderate bleeding episodes and the 95% confidence intervals for the true proportion are provided.
    End point type
    Secondary
    End point timeframe
    12 hours after first administration of study drug
    End point values
    		 Coagulation Factor VIIa (Recombinant): 75 μg/kg Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects analysed
    23 [9]
    23 [10]
    Units: proportion success of BEs
        number (confidence interval 95%)
    0.667 (0.533 to 0.800)
    0.629 (0.502 to 0.756)
    Notes
    [9] - 239 Bleeding episodes analyzed
    [10] - 307 Bleeding episodes analyzed
    No statistical analyses for this end point

    Secondary: Time to Patient Assessment of a "Good" or "Excellent" Response for Mild/Moderate Bleeding Episodes

    		 Close Top of page
    End point title
    		 Time to Patient Assessment of a "Good" or "Excellent" Response for Mild/Moderate Bleeding Episodes
    End point description
    Categories of Response to Treatment are Described as Follows: None: No noticeable effect of the treatment on the bleed or worsening of patient's condition. Continuation of treatment with the study drug was needed. Moderate: Some effect of the treatment on the bleed was noticed, e.g., pain decreased or bleeding signs improved, but bleed continued and required continued treatment with the study drug. Good: Symptoms of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage) had largely been reduced by the treatment, but had not completely disappeared. Symptoms had improved enough to not require more infusions of the study drug. Excellent: Full relief of pain and cessation of objective signs of bleed (e.g., swelling, tenderness, and decreased range of motion in the case of musculoskeletal haemorrhage). No additional infusion of study drug was required.
    End point type
    Secondary
    End point timeframe
    Within 24 hours of Bleeding Episode
    End point values
    		 Coagulation Factor VIIa (Recombinant): 75 μg/kg Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects analysed
    23 [11]
    23 [12]
    Units: hours
        median (confidence interval 95%)
    9.00 (8.92 to 11.83)
    12.00 (11.83 to 12.00)
    Notes
    [11] - 233 Bleeding episodes analyzed
    [12] - 299 Bleeding episodes analyzed
    No statistical analyses for this end point

    Secondary: Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode

    		 Close Top of page
    End point title
    		 Number of Administrations of Study Drug Per Mild/Moderate Bleeding Episode
    End point description
    The number of study drug administrations with non-missing dose information in order to treat one mild/moderate bleeding episode.
    End point type
    Secondary
    End point timeframe
    Within 24 hours of Bleeding Episode
    End point values
    		 Coagulation Factor VIIa (Recombinant): 75 μg/kg Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects analysed
    23 [13]
    23 [14]
    Units: Number of Administrations of Study Drug
        arithmetic mean (standard deviation)
    3.6 ± 2.27
    2.6 ± 2.48
    Notes
    [13] - 239 Bleeding episodes analyzed
    [14] - 307 Bleeding episodes analyzed
    No statistical analyses for this end point

    Secondary: Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode

    		 Close Top of page
    End point title
    		 Total Amount of Study Drug Administered Per Mild/Moderate Bleeding Episode
    End point description
    The total amount of study drug administered in order to treat one mild/moderate bleeding episode.
    End point type
    Secondary
    End point timeframe
    Within 24 hours of Bleeding Episode
    End point values
    		 Coagulation Factor VIIa (Recombinant): 75 μg/kg Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects analysed
    23 [15]
    23 [16]
    Units: mL per bleeding episode
        arithmetic mean (standard deviation)
    6.733 ± 6.3693
    8.287 ± 5.6531
    Notes
    [15] - 239 Bleeding episodes analyzed
    [16] - 307 Bleeding episodes analyzed
    No statistical analyses for this end point

    Other pre-specified: Mild/Moderate Bleeding Episodes With Successful Pain Relief

    		 Close Top of page
    End point title
    		 Mild/Moderate Bleeding Episodes With Successful Pain Relief
    End point description
    Successful pain relief was defined as a Visual Analogue Scale (VAS: 0-100; 0 : no pain at all; 100 : the worst pain ever possible) pain score at 12 hours after initial study drug administration that was less than the pain score at the start of treatment with study drug.
    End point type
    Other pre-specified
    End point timeframe
    12 hour after first administration of study drug
    End point values
    		 Coagulation Factor VIIa (Recombinant): 75 μg/kg Coagulation Factor VIIa (Recombinant): 225 μg/kg
    Number of subjects analysed
    23 [17]
    23 [18]
    Units: Bleeding Episodes (BEs)
    220
    275
    Notes
    [17] - 239 Bleeding episodes analyzed
    [18] - 307 Bleeding episodes analyzed
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From signing of the informed consent/assent until resolution or 30 days after the last dose of LR769 or early termination, whichever came first. The average duration for monitoring adverse event is about 11.2 months per patient.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    Coagulation Factor VIIa (recombinant): 75 μg/kg
    Reporting group description
    		 75 μg/kg treatment regimen for 3 months Coagulation FVIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX.

    Reporting group title
    Coagulation Factor VIIa (recombinant): 225 μg/kg
    Reporting group description
    		 225 μg/kg treatment regimen for 3 months Coagulation FVIIa (Recombinant): A cross over design to assess the efficacy of 2 separate dose regimens (75 μg/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 or Factor IX.

    Serious adverse events
    		 Coagulation Factor VIIa (recombinant): 75 μg/kg Coagulation Factor VIIa (recombinant): 225 μg/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 25 (8.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Nervous system disorders
    Paresis
    Additional description: The patient was diagnosed with paresis that was classified as an SAE and resolved. The investigator considered the SAE not related to study drug.
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Dysentery
    Additional description: The patient was diagnosed with dysentery that was classified as an SAE and resolved. The investigator considered the SAE not related to study drug.
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Coagulation Factor VIIa (recombinant): 75 μg/kg Coagulation Factor VIIa (recombinant): 225 μg/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 23 (52.17%)
    15 / 25 (60.00%)
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorders
    Diarrhea
         subjects affected / exposed
    1 / 23 (4.35%)
    3 / 25 (12.00%)
         occurrences all number
    1
    3
    Vomiting
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 25 (8.00%)
         occurrences all number
    1
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 23 (13.04%)
    3 / 25 (12.00%)
         occurrences all number
    4
    4
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 23 (4.35%)
    3 / 25 (12.00%)
         occurrences all number
    1
    4
    Nasopharyngitis
         subjects affected / exposed
    4 / 23 (17.39%)
    3 / 25 (12.00%)
         occurrences all number
    6
    3
    Respiratory Tract Infection Viral
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 25 (8.00%)
         occurrences all number
    2
    3
    Rhinitis
         subjects affected / exposed
    3 / 23 (13.04%)
    3 / 25 (12.00%)
         occurrences all number
    3
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Aug 2015
    This amendment included the following key changes: -Timing around treatment for severe bleeding episode was added. -Clarifying statement regarding enrollment of patients <12 years old following DMC review of PK, safety and efficacy data. -Table of Total Amount of Blood Taken during the study added to ensure awareness of the maximum allowable blood volume collection in pediatric patients. -Added exclusion criterion #10: hypersensitivity to the active substance or excipients. - Added information regarding required reporting periods for SAEs. -Added weight and dose adjustment at each 6 week visit due to pediatric patient weight fluctuation. -Added signs and symptoms of thromboembolic events as an additional safety precaution unrelated to any safety concern. -Several minor corrections were also made. This amendment was not implemented.
    26 Aug 2015
    This amendment included the following key changes: -Timing around treatment for severe bleeding episode was added. -Clarifying statement regarding enrollment of patients <12 years old following DMC review of PK, safety and efficacy data. -Table of Total Amount of Blood Taken during the study added to ensure awareness of the maximum allowable blood volume collection in pediatric patients. -Added exclusion criterion #10: hypersensitivity to the active substance or excipients. - Added information regarding required reporting periods for SAEs. -Added weight and dose adjustment at each 6 week visit due to pediatric patient weight fluctuation. -Added signs and symptoms of thromboembolic events as an additional safety precaution unrelated to any safety concern. -For completeness, “ethnicity” was added to demographics . -Several minor corrections were also made.
    09 Oct 2015
    This amendment includes the following key changes: -The LR769 surgical study (LFB-FVIIa-008-14) could only include patients younger than 12 years of age if sufficient PK, efficacy and safety data becomes available and after the DMC has reviewed these data and determined the appropriateness of including this population. This information was included for clarification that patients <12 years old would not be enrolled into the surgical study from this pediatric study until review of PK, safety and efficacy data was reviewed by the DMC.
    29 Jun 2016
    This amendment includes the following key changes: -Patient population changed from"≥ 6 months old to <12 years old" to "birth to <12 years old" at the request of regulatory agency.-A number of minor edits were made for clarification. -Slight modifications regarding PK analysis to facilitate investigators' review include details on the way population PK analysis will be performed as described in the PKAP. -Added wording to reflect a single primary efficacy endpoint. -Statement to clarify that patients in a bleeding state would be deferred from the PK part of the study to a later date was added. -Selection and timing of dose for each patient section was updated for clarity. -Statement added, "For subjects < 12 kg, the minimum weight requirement is 10.5 kg ,when blood will be collected by peripheral venipuncture. The investigator must contact the Medical Monitor to discuss enrollment of any subject weighing < 12 kg with an indwelling catheter, Port-a-cath or PICC line". -GEE and GLMM sensitivity analyses were added to align with changes made in the adult study.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 01:07:17 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA