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    Clinical Trial Results:
    A Phase 2, Open-label, Multinational Study to Evaluate the Efficacy and Safety of BMN 110 in Patients with Mucopolysaccharidosis IVA (Morquio A Syndrome) Who Have Limited Ambulation

    Summary
    EudraCT number
    2011-005703-33
    Trial protocol
    DE   GB  
    Global end of trial date
    22 Oct 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Dec 2018
    First version publication date
    13 Dec 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MOR-006
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01697319
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    BioMarin Pharmaceutical Inc.
    Sponsor organisation address
    105 Digital Drive, Novato, United States, CA 94949
    Public contact
    Clinical Trials Information, BioMarin Pharmaceutical Inc., clinicaltrials@bmrn.com
    Scientific contact
    Clinical Trials Information, BioMarin Pharmaceutical Inc., clinicaltrials@bmrn.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000973-PIP01-10
    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
    21 Apr 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Oct 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Oct 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect of 2.0 mg/kg/week BMN 110 (as defined by the domains of upper extremity function and dexterity, mobility, pain, and self care and functional abilities) in a patient population that has limited ambulation.
    Protection of trial subjects
    The study was conducted in accordance with the principles of the Declaration of Helsinki including amendments in force up to and including the time the study was conducted. The study was conducted in compliance with the International Conference on Harmonisation E6 Guideline for Good Clinical Practice, and is compliant with the European Union Clinical Trial Directive 2001/20/EC. The study was also conducted in compliance with the United States Food and Drug Administration regulations in 21 Code of Federal Regulations.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    10 Aug 2012
    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
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 6
    Country: Number of subjects enrolled
    Germany: 6
    Worldwide total number of subjects
    16
    EEA total number of subjects
    10
    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)
    0
    Children (2-11 years)
    1
    Adolescents (12-17 years)
    6
    Adults (18-64 years)
    9
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 7 study centers in 3 countries.

    Pre-assignment
    Screening details
    Subject enrolled were 16 and 1 subject withdrew from study before treatment. Treatment received subjects were 15 and 12 completed the study.

    Period 1
    Period 1 title
    BMN 110 2.0 mg/kg/week (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    BMN110 2.0 mg/kg/week
    Arm description
    BMN110 2.0 mg/kg/week intravenous infusion (approximately 4 hours) for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    BMN110
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BMN110 2.0 mg/kg/week intravenous infusion (approximately 4 hours) for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.

    Number of subjects in period 1 [1]
    BMN110 2.0 mg/kg/week
    Started
    15
    Completed
    12
    Not completed
    3
         Consent withdrawn by subject
    1
         Serious Adverse Events
    2
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Subject enrolled were 16 and 1 subject withdrew from study before treatment. Treatment received subjects were 15 and 12 completed the study.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    BMN110 2.0 mg/kg/week
    Reporting group description
    BMN110 2.0 mg/kg/week intravenous infusion (approximately 4 hours) for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.

    Reporting group values
    BMN110 2.0 mg/kg/week Total
    Number of subjects
    15 15
    Age categorical
    Units: Subjects
        5 - 11
    1 1
        12 - 18
    8 8
        >= 19
    6 6
    Age continuous
    Units: Years
        arithmetic mean (standard deviation)
    20.8 ( 8.67 ) -
    Gender categorical
    Units: Subjects
        Female
    6 6
        Male
    9 9
    Race
    Units: Subjects
        Asian
    2 2
        Black or African American
    1 1
        White
    11 11
        Other
    1 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    3 3
        Not Hispanic or Latino
    12 12
    Functional Dexterity Test-Dominant Hand
    Units: number of pegs/minute
        arithmetic mean (standard deviation)
    13.3 ( 10.86 ) -
    Functional Dexterity Test-Non-Dominant Hand
    Units: pegs/minute
        arithmetic mean (standard deviation)
    13.2 ( 12.49 ) -
    25-Foot Walk Test
    Units: Feet/Minute
        arithmetic mean (standard deviation)
    21.3 ( 31.18 ) -
    Urine Keratan Sulfate
    Urine Keratan Sulfate (n=14)
    Units: ug/mg
        arithmetic mean (standard deviation)
    16.5 ( 8.91 ) -

    End points

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    End points reporting groups
    Reporting group title
    BMN110 2.0 mg/kg/week
    Reporting group description
    BMN110 2.0 mg/kg/week intravenous infusion (approximately 4 hours) for an initial treatment phase of 48 weeks and an extension treatment phase of up to an additional 96 weeks.

    Primary: Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT)

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    End point title
    Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) [1]
    End point description
    FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute). Modified intent-to-treat (mITT) population included all subjects who received at least one dose of study medication.
    End point type
    Primary
    End point timeframe
    Up to 96 weeks
    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 sample size of the study was not determined by statistical power consideration since no statistical hypotheses were posed.
    End point values
    BMN110 2.0 mg/kg/week
    Number of subjects analysed
    15
    Units: % of change
    arithmetic mean (standard deviation)
        Week 12: Dominant Hand (n=15)
    -2.9 ( 41.37 )
        Week 24: Dominant Hand (n=15)
    1.8 ( 45.60 )
        Week 36: Dominant Hand (n=14)
    11.2 ( 48.21 )
        Week 48: Dominant Hand (n=13)
    23.1 ( 53.88 )
        Week 72: Dominant Hand (n=9)
    37.2 ( 54.94 )
        Week 96: Dominant Hand (n=3)
    22.5 ( 42.21 )
        Week 12: Non-dominant Hand (n=14)
    11.5 ( 36.84 )
        Week 24: Non-dominant Hand (n=14)
    13.8 ( 32.54 )
        Week 36: Non-dominant Hand (n=13)
    9.3 ( 20.55 )
        Week 48: Non-dominant Hand (n=12)
    6.0 ( 35.78 )
        Week 72: Non-dominant Hand (n=8)
    49.3 ( 126.26 )
        Week 96: Non-dominant Hand (n=2)
    -2.0 ( 2.83 )
    No statistical analyses for this end point

    Primary: Change From Baseline in Strength as Assessed by Grip Test

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    End point title
    Change From Baseline in Strength as Assessed by Grip Test [2]
    End point description
    A grip-strength dynamometer was used to measure grip strength of dominant and non-dominant hands in the forearm and wrist supported position. mITT population.
    End point type
    Primary
    End point timeframe
    Up to Week 96
    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: The sample size of the study was not determined by statistical power consideration since no statistical hypotheses were posed.
    End point values
    BMN110 2.0 mg/kg/week
    Number of subjects analysed
    15
    Units: Kg
    arithmetic mean (standard deviation)
        Baseline (n=10)
    1.3 ( 0.90 )
        Week 12: Dominant Hand (n=10)
    0.1 ( 0.90 )
        Week 24: Dominant Hand (n=10)
    0.1 ( 0.89 )
        Week 36: Dominant Hand (n=8)
    -0.1 ( 0.87 )
        Week 48: Dominant Hand (n=9)
    -0.3 ( 0.90 )
        Week 72: Dominant Hand (n=6)
    -0.1 ( 0.33 )
        Week 96: Dominant Hand (n=3)
    0.3 ( 0.23 )
        Week 12: Non-dominant Hand (n=10)
    0.1 ( 0.66 )
        Week 24: Non-dominant Hand (n=10)
    -0.0 ( 0.70 )
        Week 36: Non-dominant Hand (n=8)
    0.0 ( 0.73 )
        Week 48: Non-dominant Hand (n=9)
    -0.1 ( 0.66 )
        Week 72: Non-dominant Hand (n=6)
    0.1 ( 0.79 )
        Week 96: Non-dominant Hand (n=3)
    0.4 ( 0.87 )
    No statistical analyses for this end point

    Primary: Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT)

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    End point title
    Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT) [3]
    End point description
    The 25FWT is an assessment of mobility and leg function performance based on a timed 25-foot walk. The subject was directed to one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly as possible, but safely. The time was calculated from the initiation of the instruction to start and ended when the subject reached the 25-foot mark. The task was immediately administered again by having the subject walk back the same distance. Subjects could use assistive devices when doing this task. In addition, subjects could “walk” on their knees if this was their usual method of ambulation. The score for the 25FWT was the average of the two completed attempts. mITT population.
    End point type
    Primary
    End point timeframe
    Up to Week 72
    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: The sample size of the study was not determined by statistical power consideration since no statistical hypotheses were posed.
    End point values
    BMN110 2.0 mg/kg/week
    Number of subjects analysed
    15
    Units: % of change
    arithmetic mean (standard deviation)
        Week 24 (n=8)
    95.7 ( 142.37 )
        Week 48 (n=7)
    53.5 ( 102.74 )
        Week 72 (n=4)
    48.3 ( 145.01 )
    No statistical analyses for this end point

    Primary: Change from Baseline in Strength as Assessed by Pinch Test

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    End point title
    Change from Baseline in Strength as Assessed by Pinch Test [4]
    End point description
    A pinch meter was used to measure pinch strength of dominant and non-dominant hands in the forearm and wrist supported position. Each subject was tested with the elbow at 90°, the forearm neutral, and the wrist in neutral deviation. mITT population. For Pinch Dominant Hand Week 96 One observation only.
    End point type
    Primary
    End point timeframe
    Up to Week 96
    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: The sample size of the study was not determined by statistical power consideration since no statistical hypotheses were posed.
    End point values
    BMN110 2.0 mg/kg/week
    Number of subjects analysed
    15
    Units: Kg
    arithmetic mean (standard deviation)
        Baseline: Dominant Hand (n=10)
    0.6 ( 0.36 )
        Week 12: Dominant Hand (n=9)
    0.0 ( 0.26 )
        Week 24: Dominant Hand (n=9)
    -0.1 ( 0.32 )
        Week 36: Dominant Hand (n=8)
    -0.0 ( 0.22 )
        Week 48: Dominant Hand (n=9)
    -0.0 ( 0.30 )
        Week 72: Dominant Hand (n=7)
    -0.1 ( 0.23 )
        Week 96: Dominant Hand (n=1)
    -0.6 ( 0 )
        Baseline: Non Dominant Hand (n=10)
    0.5 ( 0.39 )
        Week 12: Non-dominant Hand (n=9)
    0.1 ( 0.21 )
        Week 24: Non-dominant Hand (n=9)
    -0.0 ( 0.18 )
        Week 36: Non-dominant Hand (n=8)
    0.0 ( 0.19 )
        Week 48: Non-dominant Hand (n=9)
    0.0 ( 0.27 )
        Week 72: Non-dominant Hand (n=7)
    -0.1 ( 0.31 )
        Week 96: Non-dominant Hand (n=2)
    -0.3 ( 0.36 )
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)

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    End point title
    Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS)
    End point description
    Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. Urine Keratan Sulfate (uKS) is normalized to creatinine. mITT population.
    End point type
    Secondary
    End point timeframe
    Up to Week 96
    End point values
    BMN110 2.0 mg/kg/week
    Number of subjects analysed
    15
    Units: % of change
    arithmetic mean (standard deviation)
        Week 24 (n=15)
    -47.7 ( 15.4 )
        Week 48 (n=15)
    -43.4 ( 24.82 )
        Week 72(n=9)
    -45.5 ( 19.67 )
        Week 96 (n=3)
    -48.3 ( 24.13 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Week 144
    Adverse event reporting additional description
    Safety population.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    BMN110 2.0 mg/kg/week
    Reporting group description
    -

    Serious adverse events
    BMN110 2.0 mg/kg/week
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 15 (46.67%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Poor venous access
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    Central venous catheterisation
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Cervical cord compression
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone disorder
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    BMN110 2.0 mg/kg/week
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 15 (100.00%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Hypotension
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Pallor
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Poor venous access
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Surgical and medical procedures
    Tooth extraction
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    General disorders and administration site conditions
    Catheter site pain
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Device occlusion
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Chest pain
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Extravasation
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Face oedema
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Fatigue
         subjects affected / exposed
    4 / 15 (26.67%)
         occurrences all number
    5
    Feeling cold
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Influenza like illness
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Infusion site extravasation
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Infusion site pain
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    3
    Injection site pain
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Infusion site reaction
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    5
    Localised oedema
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Malaise
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Medical device pain
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Nodule
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    5
    Oedema peripheral
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Pyrexia
         subjects affected / exposed
    9 / 15 (60.00%)
         occurrences all number
    26
    Pain
         subjects affected / exposed
    4 / 15 (26.67%)
         occurrences all number
    5
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Anaphylactic reaction
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Anaphylactoid reaction
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Hypersensitivity
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Reaction to colouring
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Seasonal allergy
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    3
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Cough
         subjects affected / exposed
    6 / 15 (40.00%)
         occurrences all number
    15
    Dyspnoea
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    4
    Hypoxia
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Nasal congestion
         subjects affected / exposed
    5 / 15 (33.33%)
         occurrences all number
    10
    Nasal obstruction
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Oropharyngeal pain
         subjects affected / exposed
    4 / 15 (26.67%)
         occurrences all number
    14
    Respiratory failure
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Restrictive pulmonary disease
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Rhinorrhoea
         subjects affected / exposed
    3 / 15 (20.00%)
         occurrences all number
    3
    Tachypnoea
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Sinus congestion
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Throat irritation
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Wheezing
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    3
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Depressed mood
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Depression
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Restlessness
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Blood bilirubin increased
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Body temperature increased
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Blood glucose increased
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Electrocardiogram PR prolongation
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    QRS axis abnormal
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Weight increased
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Chillblains
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Fall
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    3
    Heat exhaustion
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Limb injury
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Tooth fracture
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Cardiac disorders
    Atrioventricular block first degree
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Sinus tachycardia
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Tachycardia
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Nervous system disorders
    Burning sensation
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Clonus
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Dizziness
         subjects affected / exposed
    4 / 15 (26.67%)
         occurrences all number
    10
    Hypoaesthesia
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    3
    Headache
         subjects affected / exposed
    11 / 15 (73.33%)
         occurrences all number
    42
    Lethargy
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    3
    Somnolence
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Paraesthesia
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Ear pain
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    3
    Ear disorder
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Otorrhoea
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Eye disorders
    Corneal opacity
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Dry eye
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Eye disorder
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Eye pain
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Eye pruritus
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Eyelid cyst
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Eyelid pain
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Lacrimation increased
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    3
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    3
    Abdominal pain upper
         subjects affected / exposed
    6 / 15 (40.00%)
         occurrences all number
    12
    Abdominal pain
         subjects affected / exposed
    3 / 15 (20.00%)
         occurrences all number
    7
    Constipation
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Gastritis
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Diarrhoea
         subjects affected / exposed
    7 / 15 (46.67%)
         occurrences all number
    28
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    7 / 15 (46.67%)
         occurrences all number
    19
    Vomiting
         subjects affected / exposed
    6 / 15 (40.00%)
         occurrences all number
    29
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Dermatitis
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Dermatitis allergic
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Erythema
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Pigmentation disorder
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Pruritus
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    6
    Pruritus generalised
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Rash follicular
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Rash
         subjects affected / exposed
    3 / 15 (20.00%)
         occurrences all number
    3
    Skin disorder
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    3
    Dysuria
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 15 (33.33%)
         occurrences all number
    28
    Back pain
         subjects affected / exposed
    5 / 15 (33.33%)
         occurrences all number
    16
    Flank pain
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Musculoskeletal pain
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    5
    Myalgia
         subjects affected / exposed
    4 / 15 (26.67%)
         occurrences all number
    8
    Neck pain
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Pubic pain
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Pain in extremity
         subjects affected / exposed
    5 / 15 (33.33%)
         occurrences all number
    8
    Sensation of heaviness
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Tenosynovitis
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Cystitis
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Ear infection
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    5
    Eye infection
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Gastroenteritis
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    2
    Hordeolum
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 15 (20.00%)
         occurrences all number
    4
    Otitis externa fungal
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Otitis media
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2
    Nasopharyngitis
         subjects affected / exposed
    9 / 15 (60.00%)
         occurrences all number
    19
    Periodontitis
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Pulpitis dental
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Rhinitis
         subjects affected / exposed
    2 / 15 (13.33%)
         occurrences all number
    3
    Sinusitis
         subjects affected / exposed
    3 / 15 (20.00%)
         occurrences all number
    4
    Skin candida
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 15 (46.67%)
         occurrences all number
    14
    Subcutaneous abscess
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    6
    Viral infection
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 15 (6.67%)
         occurrences all number
    2

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Mar 2013
    Other than protocol clarifications and administrative changes, the following items were revised: 1. An extension treatment phase was added to the existing protocol, to permit subjects to continue to receive study drug past the completion of the initial treatment phase without enrolling in a new study. 2. The sleep study was extended to include all eligible subjects, with no minimum or maximum cap on enrollment. 3. Cardiopulmonary exercise testing (CPET) and plasma keratan sulfate (KS) collection were removed from the study. CPET was removed because, due to the required limitations on ambulatory capacity as an enrollment criterion for the study, none of the enrolled subjects were physically capable of performing the CPET testing. Plasma KS was removed based on findings from other BMN 110 studies which showed no meaningful results from the test. 4. Certain assessments (genu valgum, kyphosis, radius length) were removed from the standard physical examination. 5. Changes were made to the language surrounding collection of biomarkers of bone and cartilage metabolism, as well as language surrounding the timing of collection of drug-specific IgE following a possible hypersensitivity reaction, to make the language in MOR-006 consistent with other BMN 110 study protocols.
    12 Jun 2013
    Other than protocol clarifications and administrative changes, the following items were revised: 1. Language regarding imaging scans at the termination visits was clarified to make it clear that subjects at that visit needed to receive either a cervical spine radiograph or an MRI (not both), and that DXA would not be performed at the termination visit for the extension phase. 2. Background information was updated to include the results from the Phase 3 studies, MOR-004 and MOR-005, as well as additional updated safety information. In addition, the rationale for the 2.0 mg/kg/week dose was updated based on the results of MOR-004 and MOR-005. 3. An interim CSR, to be completed when all subjects have completed Week 48, was added. 4. The list of BMN 110 excipients was updated to reflect those included in the Phase 3/commercial formulation. 5. The Allergic Reaction Review Board (ARRB) language was modified; ARRB approval was no longer required in order to determine what (if any) blood sampling should be performed in response to possible hypersensitivity reactions. This change was made based on experience in other BMN 110 studies.

    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.
    The study was terminated after all subjects had the opportunity to complete the initial treatment phase (Week 48 visit). The N is reduced beyond Week 48 due to the staggered accrual and efficacy reporting.
    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.

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