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   43850   clinical trials with a EudraCT protocol, of which   7282   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 2b, Randomized, Double-blind, Placebo-controlled Study of NEOD001 in Previously Treated Subjects with Light Chain (AL) Amyloidosis who have Persistent Cardiac Dysfunction

    Summary
    EudraCT number
    2015-004318-14
    Trial protocol
    DE   GB   GR   ES   AT  
    Global end of trial date
    05 Mar 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    06 Dec 2018
    First version publication date
    03 Sep 2018
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    The numbers relating to the non-serious adverse events have been updated.

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    NEOD001-201
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02632786
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Prothena Therapeutics Limited
    Sponsor organisation address
    Adelphi Plaza, Upper George's Street, Co. Dublin, Dun Laoghaire, Ireland, A96 T927
    Public contact
    Communications Office, Prothena Biosciences Inc, info@prothena.com
    Scientific contact
    Clinical Trials Office, Prothena Biosciences Inc, info@prothena.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    23 Apr 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Mar 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Mar 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study is to determine the efficacy and safety of NEOD001 versus placebo in subjects with AL amyloidosis who have persistent cardiac dysfunction.
    Protection of trial subjects
    This study was conducted in compliance with International Conference on Harmonisation (ICH) Good Clinical Practice, the principles of the Declaration of Helsinki, and with the laws of the countries in which the study was conducted. The Investigator had the ability to break the blind for a specific subject in the event of an immediate medical emergency, wherein knowledge of the subject’s treatment (NEOD001 or placebo) needed to be known in order to provide adequate medical treatment. In these situations, the breaking of the blind was to be reported to the Sponsor or its designee within 24 hours. An independent Safety Monitoring Committee (SMC) was used during the study, it consisted of at least 2 clinicians and a biostatistician not directly involved with the conduct of the trial. The SMC met at defined timepoints to review specified blinded subject data during the conduct of the study. The purpose of these independent data reviews was to assess the totality of the safety data and provide a recommendation to the Sponsor for continuation of dosing or protocol modifications. A non-scheduled meeting could be called at the discretion of the Chairperson or the request of the Sponsor.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    04 Jan 2016
    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
    Spain: 11
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    Austria: 2
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 13
    Country: Number of subjects enrolled
    Greece: 11
    Country: Number of subjects enrolled
    Australia: 9
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Italy: 8
    Country: Number of subjects enrolled
    United States: 57
    Worldwide total number of subjects
    129
    EEA total number of subjects
    55
    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)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    70
    From 65 to 84 years
    59
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    A total of 129 subjects were enrolled in the study, 66 randomly assigned to receive NEOD001 and 63 randomly assigned to receive placebo. A total of 111 (86.0%) subjects completed the study and 18 (14.0%) subjects discontinued the study. In the EEA there were a total of 55 subjects randomized.

    Pre-assignment
    Screening details
    Screening evaluations and procedures were performed within 28 days prior to the first study drug administration on Month 1-Day 1. Individual test results that did not meet eligibility requirements could be repeated, with the exception of 6MWT; full rescreening was only allowed once per subject.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    NEOD001 24 mg/kg
    Arm description
    NEOD001, 24 mg/kg IV every 4 weeks for 12 months
    Arm type
    Experimental

    Investigational medicinal product name
    NEOD001 24 mg/kg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Study drug administered intravenously every 4 weeks for 12 months, starting at the Month 1-Day 1 Visit. Subjects received up to 12 infusions of study drug.

    Arm title
    Placebo
    Arm description
    Placebo, 0.9% Saline IV every 4 weeks for 12 months
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous drip use (Noncurrent)

    Number of subjects in period 1
    NEOD001 24 mg/kg Placebo
    Started
    66
    63
    Completed
    55
    56
    Not completed
    11
    7
         Consent withdrawn by subject
    1
    -
         Physician decision
    5
    4
         Adverse event, non-fatal
    2
    1
         Death
    3
    2

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    NEOD001 24 mg/kg
    Reporting group description
    NEOD001, 24 mg/kg IV every 4 weeks for 12 months

    Reporting group title
    Placebo
    Reporting group description
    Placebo, 0.9% Saline IV every 4 weeks for 12 months

    Reporting group values
    NEOD001 24 mg/kg Placebo Total
    Number of subjects
    66 63 129
    Age categorical
    Units: Subjects
        From 65-84 years
    25 34 59
        From 18-64 Years
    41 29 70
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    62.09 ( 9.188 ) 63.90 ( 8.332 ) -
    Gender categorical
    Units: Subjects
        Female
    27 24 51
        Male
    39 39 78
    Race
    Units: Subjects
        White
    61 56 117
        Black or African American
    3 2 5
        Not Reported
    0 2 2
        Arab
    1 0 1
        Asian
    1 0 1
        Indian
    0 1 1
        North African, Bereber
    0 1 1
        Persian
    0 1 1
    Ethnicity
    Units: Subjects
        Not Reported
    2 2 4
        Not Hispanic or Latino
    64 61 125
    Subject analysis sets

    Subject analysis set title
    NEOD001 24 mg/kg (Safety Population)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Safety Population includes all subjects who received any amount of study drug

    Subject analysis set title
    NEOD001 24 mg/kg (ITT Population)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    ITT Population includes all randomized subjects who received any amount of study drug

    Subject analysis set title
    NEOD001 24 mg/kg (Renal Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Renal Evaluable Population includes all ITT subjects who had a baseline proteinuria >0.5 g/24 hours and at least one postbaseline assessment of 24 hour protein

    Subject analysis set title
    NEOD001 24 mg/kg (Peripheral Neuropathy Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Peripheral Neuropathy Evaluable Population includes all ITT subjects who had ascending sensorimotor neuropathy due to AL amyloidosis at screening and had a baseline NIS-LL total score >= 2 and at least one postbaseline NIS-LL total score assessment

    Subject analysis set title
    NEOD001 24 mg/kg (Hepatic Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Hepatic Evaluable Population includes all ITT subjects who had a baseline alkaline phosphatase >1.5 × ULN and at least one postbaseline assessment of alkaline phosphatase

    Subject analysis set title
    Placebo (Safety Population)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Safety Population includes all subjects who received any amount of study drug

    Subject analysis set title
    Placebo (ITT Population)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    ITT Population includes all randomized subjects who received any amount of study drug

    Subject analysis set title
    Placebo (Renal Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Renal Evaluable Population includes all ITT subjects who had a baseline proteinuria >0.5 g/24 hours and at least one postbaseline assessment of 24 hour protein

    Subject analysis set title
    Placebo (Peripheral Neuropathy Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Peripheral Neuropathy Evaluable Population includes all ITT subjects who had ascending sensorimotor neuropathy due to AL amyloidosis at screening and had a baseline NIS-LL total score >= 2 and at least one postbaseline NIS-LL total score assessment

    Subject analysis set title
    Placebo (Hepatic Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Hepatic Evaluable Population includes all ITT subjects who had a baseline alkaline phosphatase >1.5 × ULN and at least one postbaseline assessment of alkaline phosphatase

    Subject analysis sets values
    NEOD001 24 mg/kg (Safety Population) NEOD001 24 mg/kg (ITT Population) NEOD001 24 mg/kg (Renal Evaluable Population) NEOD001 24 mg/kg (Peripheral Neuropathy Evaluable Population) NEOD001 24 mg/kg (Hepatic Evaluable Population) Placebo (Safety Population) Placebo (ITT Population) Placebo (Renal Evaluable Population) Placebo (Peripheral Neuropathy Evaluable Population) Placebo (Hepatic Evaluable Population)
    Number of subjects
    66
    66
    13
    12
    5
    63
    63
    18
    14
    4
    Age categorical
    Units: Subjects
        From 65-84 years
    25
    25
    5
    6
    1
    34
    34
    9
    8
    0
        From 18-64 Years
    41
    41
    8
    6
    4
    29
    29
    9
    6
    4
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    62.09 ( 9.188 )
    62.09 ( 9.188 )
    64.21 ( 8.372 )
    62.70 ( 9.962 )
    58.29 ( 9.811 )
    63.90 ( 8.332 )
    63.90 ( 8.332 )
    63.28 ( 9.157 )
    64.85 ( 6.481 )
    60.12 ( 3.419 )
    Gender categorical
    Units: Subjects
        Female
    27
    27
    3
    4
    3
    24
    24
    6
    4
    0
        Male
    39
    39
    10
    8
    2
    39
    39
    12
    10
    4
    Race
    Units: Subjects
        White
    61
    61
    13
    12
    5
    56
    56
    16
    14
    4
        Black or African American
    3
    3
    0
    0
    0
    2
    2
    1
    0
    0
        Not Reported
    0
    0
    0
    0
    0
    2
    2
    0
    0
    0
        Arab
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
        Asian
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
        Indian
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
        North African, Bereber
    0
    0
    0
    0
    0
    1
    1
    1
    0
    0
        Persian
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    Ethnicity
    Units: Subjects
        Not Reported
    2
    2
    1
    0
    1
    2
    2
    0
    1
    0
        Not Hispanic or Latino
    64
    64
    12
    12
    4
    61
    61
    18
    13
    4

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    NEOD001 24 mg/kg
    Reporting group description
    NEOD001, 24 mg/kg IV every 4 weeks for 12 months

    Reporting group title
    Placebo
    Reporting group description
    Placebo, 0.9% Saline IV every 4 weeks for 12 months

    Subject analysis set title
    NEOD001 24 mg/kg (Safety Population)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Safety Population includes all subjects who received any amount of study drug

    Subject analysis set title
    NEOD001 24 mg/kg (ITT Population)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    ITT Population includes all randomized subjects who received any amount of study drug

    Subject analysis set title
    NEOD001 24 mg/kg (Renal Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Renal Evaluable Population includes all ITT subjects who had a baseline proteinuria >0.5 g/24 hours and at least one postbaseline assessment of 24 hour protein

    Subject analysis set title
    NEOD001 24 mg/kg (Peripheral Neuropathy Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Peripheral Neuropathy Evaluable Population includes all ITT subjects who had ascending sensorimotor neuropathy due to AL amyloidosis at screening and had a baseline NIS-LL total score >= 2 and at least one postbaseline NIS-LL total score assessment

    Subject analysis set title
    NEOD001 24 mg/kg (Hepatic Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Hepatic Evaluable Population includes all ITT subjects who had a baseline alkaline phosphatase >1.5 × ULN and at least one postbaseline assessment of alkaline phosphatase

    Subject analysis set title
    Placebo (Safety Population)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Safety Population includes all subjects who received any amount of study drug

    Subject analysis set title
    Placebo (ITT Population)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    ITT Population includes all randomized subjects who received any amount of study drug

    Subject analysis set title
    Placebo (Renal Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Renal Evaluable Population includes all ITT subjects who had a baseline proteinuria >0.5 g/24 hours and at least one postbaseline assessment of 24 hour protein

    Subject analysis set title
    Placebo (Peripheral Neuropathy Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Peripheral Neuropathy Evaluable Population includes all ITT subjects who had ascending sensorimotor neuropathy due to AL amyloidosis at screening and had a baseline NIS-LL total score >= 2 and at least one postbaseline NIS-LL total score assessment

    Subject analysis set title
    Placebo (Hepatic Evaluable Population)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Hepatic Evaluable Population includes all ITT subjects who had a baseline alkaline phosphatase >1.5 × ULN and at least one postbaseline assessment of alkaline phosphatase

    Primary: Cardiac Best Response

    Close Top of page
    End point title
    Cardiac Best Response
    End point description
    N-terminal pro-brain natriuretic peptide (NT-proBNP) best response (Response or Non-Response [Stable, Progression]) from baseline through 12 months of treatment
    End point type
    Primary
    End point timeframe
    Baseline through 12 months of treatment
    End point values
    NEOD001 24 mg/kg (ITT Population) Placebo (ITT Population)
    Number of subjects analysed
    66
    63
    Units: Subjects
        Response
    26
    30
        Non-Response
    40
    33
    Statistical analysis title
    Primary Eff Endpt: Cardiac Best Resp thru 12m Tx
    Statistical analysis description
    Test to determine if the percentage of NT-proBNP best responders through 12 months of treatment is the same or different between placebo and NEOD001.
    Comparison groups
    NEOD001 24 mg/kg (ITT Population) v Placebo (ITT Population)
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.319
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Risk ratio (RR)
    Point estimate
    0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.55
         upper limit
    1.21

    Secondary: SF-36v2 PCS Score

    Close Top of page
    End point title
    SF-36v2 PCS Score
    End point description
    Change in Short Form-36 (SF-36v2) Questionnaire Physical Component Summary (PCS) Score; the lower the score the more disability
    End point type
    Secondary
    End point timeframe
    Baseline to 12 months of treatment
    End point values
    NEOD001 24 mg/kg (ITT Population) Placebo (ITT Population)
    Number of subjects analysed
    66
    63
    Units: SF-36v2 PCS Score
    least squares mean (confidence interval 95%)
        SF-36v2 PCS Score
    0.19 (-1.83 to 2.22)
    0.97 (-0.99 to 2.93)
    Statistical analysis title
    Change from Baseline SF-36v2 PCS Score to 12m Tx
    Statistical analysis description
    Test to determine if the mean change from baseline in the SF-36v2 PCS score after 12 months of treatment is the same or different between placebo and NEOD001.
    Comparison groups
    NEOD001 24 mg/kg (ITT Population) v Placebo (ITT Population)
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.5563
    Method
    Mixed models analysis
    Parameter type
    Mean difference (net)
    Point estimate
    -0.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.37
         upper limit
    1.81

    Secondary: 6MWT Distance

    Close Top of page
    End point title
    6MWT Distance
    End point description
    Change in 6 Minute Walk Test (6MWT) Distance (meters)
    End point type
    Secondary
    End point timeframe
    Baseline to 12 months of treatment
    End point values
    NEOD001 24 mg/kg (ITT Population) Placebo (ITT Population)
    Number of subjects analysed
    66
    63
    Units: meters
    median (inter-quartile range (Q1-Q3))
        6MWT Distance (meters)
    19.25 (-21.75 to 59.37)
    8.00 (-24.99 to 47.24)
    Statistical analysis title
    Change from Baseline in 6MWT Distance to 12m Tx
    Statistical analysis description
    Test to determine if mean ranked change from baseline in 6MWT distance (meters) after 12 months of treatment is the same or different between placebo and NEOD001.
    Comparison groups
    NEOD001 24 mg/kg (ITT Population) v Placebo (ITT Population)
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8992
    Method
    ANCOVA
    Parameter type
    Median difference (net)
    Point estimate
    5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.5
         upper limit
    23

    Secondary: NT-proBNP Slope

    Close Top of page
    End point title
    NT-proBNP Slope
    End point description
    Rate of change in NT-proBNP (ng/L per infusion)
    End point type
    Secondary
    End point timeframe
    Baseline through 12 Months of Treatment
    End point values
    NEOD001 24 mg/kg (ITT Population) Placebo (ITT Population)
    Number of subjects analysed
    66
    63
    Units: ng/L per infusion
    least squares mean (confidence interval 95%)
        NT-proBNP (ng/L per infusion)
    9.45 (-45.66 to 64.55)
    81.41 (25.15 to 137.68)
    Statistical analysis title
    NT-proBNP (ng/L) Rate of Change thru 12m Tx
    Statistical analysis description
    Test to determine if the rate of change (i.e., slope) of NT-proBNP over 12 months of treatment is the same or different between placebo and NEOD001.
    Comparison groups
    NEOD001 24 mg/kg (ITT Population) v Placebo (ITT Population)
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0729
    Method
    Mixed models analysis
    Parameter type
    Slope
    Point estimate
    -71.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -150.72
         upper limit
    6.79

    Secondary: Renal Best Response

    Close Top of page
    End point title
    Renal Best Response
    End point description
    Proteinuria and estimated Glomerular Filtration Rate (eGFR) response (Response or Non-Response [Stable, Progression]) from baseline through 12 months of treatment in subjects with renal involvement
    End point type
    Secondary
    End point timeframe
    Baseline through 12 months of treatment
    End point values
    NEOD001 24 mg/kg (Renal Evaluable Population) Placebo (Renal Evaluable Population)
    Number of subjects analysed
    13
    18
    Units: Count of Participants
        Response
    7
    6
        Non-Response
    6
    12
    Statistical analysis title
    Renal Best Response thru 12m of Tx
    Statistical analysis description
    Test to determine if the percentage of renal best responders through 12 months of treatment is the same or different between placebo and NEOD001.
    Comparison groups
    NEOD001 24 mg/kg (Renal Evaluable Population) v Placebo (Renal Evaluable Population)
    Number of subjects included in analysis
    31
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3529
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Risk ratio (RR)
    Point estimate
    1.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.6
         upper limit
    3.94

    Secondary: NIS-LL Total Score

    Close Top of page
    End point title
    NIS-LL Total Score
    End point description
    Change in Neuropathy Impairment Score-Lower Limb (NIS-LL) Total Score in subjects with peripheral nerve involvement
    End point type
    Secondary
    End point timeframe
    Baseline to 12 months of treatment
    End point values
    NEOD001 24 mg/kg (Peripheral Neuropathy Evaluable Population) Placebo (Peripheral Neuropathy Evaluable Population)
    Number of subjects analysed
    12
    14
    Units: NIS-LL Total Score
    least squares mean (confidence interval 95%)
        NIS-LL Total Score
    -1.2 (-3.9 to 1.6)
    -0.6 (-3.0 to 1.8)
    Statistical analysis title
    Change from Baseline in NIS-LL Total Score to 12m
    Statistical analysis description
    Test to determine if the mean change from baseline in NIS-LL total score after 12 months of treatment is the same or different between placebo and NEOD001.
    Comparison groups
    NEOD001 24 mg/kg (Peripheral Neuropathy Evaluable Population) v Placebo (Peripheral Neuropathy Evaluable Population)
    Number of subjects included in analysis
    26
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.757
    Method
    Mixed models analysis
    Parameter type
    Mean difference (net)
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.2
         upper limit
    3

    Secondary: Hepatic Best Response

    Close Top of page
    End point title
    Hepatic Best Response
    End point description
    Alkaline Phosphatase response (Response or Non-Response [Stable, Progression]) from baseline through 12 months of treatment in subjects with hepatic involvement
    End point type
    Secondary
    End point timeframe
    Baseline through 12 months of treatment
    End point values
    NEOD001 24 mg/kg (Hepatic Evaluable Population) Placebo (Hepatic Evaluable Population)
    Number of subjects analysed
    5
    4
    Units: Count of Participants
        Response
    1
    0
        Non-Response
    4
    4
    Statistical analysis title
    Hepatic Best Response thru 12m of Tx
    Statistical analysis description
    Test to determine if the percentage of hepatic best responders through 12 months of treatment is the same or different between placebo and NEOD001.
    Comparison groups
    NEOD001 24 mg/kg (Hepatic Evaluable Population) v Placebo (Hepatic Evaluable Population)
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4142
    Method
    Cochran-Mantel-Haenszel
    Confidence interval

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Initiation of study drug through the last study visit or up to 30 days after date of last dose
    Adverse event reporting additional description
    AE that newly appears, increases in frequency, or worsens in severity following initiation of study
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    NEOD001 24 mg/kg
    Reporting group description
    NEOD001, 24 mg/kg IV every 4 weeks for 12 months

    Reporting group title
    Placebo
    Reporting group description
    Placebo, 0.9% Saline IV every 4 weeks for 12 months

    Reporting group title
    Total
    Reporting group description
    NEOD001 + Placebo

    Serious adverse events
    NEOD001 24 mg/kg Placebo Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 66 (21.21%)
    15 / 63 (23.81%)
    29 / 129 (22.48%)
         number of deaths (all causes)
    2
    2
    4
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant urinary tract neoplasm
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 66 (0.00%)
    2 / 63 (3.17%)
    2 / 129 (1.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Sudden death
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 66 (3.03%)
    1 / 63 (1.59%)
    3 / 129 (2.33%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 66 (3.03%)
    1 / 63 (1.59%)
    3 / 129 (2.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 63 (0.00%)
    2 / 129 (1.55%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 63 (0.00%)
    2 / 129 (1.55%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 66 (0.00%)
    3 / 63 (4.76%)
    3 / 129 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Encephalopathy
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 63 (0.00%)
    2 / 129 (1.55%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 66 (1.52%)
    3 / 63 (4.76%)
    4 / 129 (3.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Ureteric obstruction
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 66 (3.03%)
    1 / 63 (1.59%)
    3 / 129 (2.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 66 (0.00%)
    4 / 63 (6.35%)
    4 / 129 (3.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Fluid overload
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 63 (1.59%)
    2 / 129 (1.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic syndrome
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 63 (0.00%)
    1 / 129 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    NEOD001 24 mg/kg Placebo Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    58 / 66 (87.88%)
    52 / 63 (82.54%)
    110 / 129 (85.27%)
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    2 / 66 (3.03%)
    4 / 63 (6.35%)
    6 / 129 (4.65%)
         occurrences all number
    2
    5
    7
    Vascular disorders
    Hypotension
         subjects affected / exposed
    2 / 66 (3.03%)
    4 / 63 (6.35%)
    6 / 129 (4.65%)
         occurrences all number
    3
    4
    7
    Hypertension
         subjects affected / exposed
    3 / 66 (4.55%)
    5 / 63 (7.94%)
    8 / 129 (6.20%)
         occurrences all number
    3
    6
    9
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 66 (7.58%)
    8 / 63 (12.70%)
    13 / 129 (10.08%)
         occurrences all number
    6
    11
    17
    Headache
         subjects affected / exposed
    9 / 66 (13.64%)
    6 / 63 (9.52%)
    15 / 129 (11.63%)
         occurrences all number
    11
    7
    18
    Hypoaesthesia
         subjects affected / exposed
    5 / 66 (7.58%)
    2 / 63 (3.17%)
    7 / 129 (5.43%)
         occurrences all number
    6
    2
    8
    Paraesthesia
         subjects affected / exposed
    4 / 66 (6.06%)
    3 / 63 (4.76%)
    7 / 129 (5.43%)
         occurrences all number
    4
    3
    7
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 66 (9.09%)
    11 / 63 (17.46%)
    17 / 129 (13.18%)
         occurrences all number
    6
    14
    20
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    14 / 66 (21.21%)
    14 / 63 (22.22%)
    28 / 129 (21.71%)
         occurrences all number
    15
    26
    41
    Oedema peripheral
         subjects affected / exposed
    7 / 66 (10.61%)
    8 / 63 (12.70%)
    15 / 129 (11.63%)
         occurrences all number
    7
    12
    19
    Pyrexia
         subjects affected / exposed
    4 / 66 (6.06%)
    4 / 63 (6.35%)
    8 / 129 (6.20%)
         occurrences all number
    4
    4
    8
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    3 / 66 (4.55%)
    4 / 63 (6.35%)
    7 / 129 (5.43%)
         occurrences all number
    3
    5
    8
    Constipation
         subjects affected / exposed
    7 / 66 (10.61%)
    6 / 63 (9.52%)
    13 / 129 (10.08%)
         occurrences all number
    9
    8
    17
    Diarrhoea
         subjects affected / exposed
    13 / 66 (19.70%)
    11 / 63 (17.46%)
    24 / 129 (18.60%)
         occurrences all number
    15
    12
    27
    Nausea
         subjects affected / exposed
    6 / 66 (9.09%)
    14 / 63 (22.22%)
    20 / 129 (15.50%)
         occurrences all number
    6
    15
    21
    Vomiting
         subjects affected / exposed
    6 / 66 (9.09%)
    4 / 63 (6.35%)
    10 / 129 (7.75%)
         occurrences all number
    7
    4
    11
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    8 / 66 (12.12%)
    6 / 63 (9.52%)
    14 / 129 (10.85%)
         occurrences all number
    9
    8
    17
    Dyspnoea
         subjects affected / exposed
    7 / 66 (10.61%)
    7 / 63 (11.11%)
    14 / 129 (10.85%)
         occurrences all number
    7
    9
    16
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 66 (3.03%)
    5 / 63 (7.94%)
    7 / 129 (5.43%)
         occurrences all number
    3
    6
    9
    Rash macular
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences all number
    0
    11
    11
    Urticaria
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 63 (1.59%)
    1 / 129 (0.78%)
         occurrences all number
    0
    8
    8
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    5 / 66 (7.58%)
    2 / 63 (3.17%)
    7 / 129 (5.43%)
         occurrences all number
    5
    2
    7
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 66 (7.58%)
    4 / 63 (6.35%)
    9 / 129 (6.98%)
         occurrences all number
    6
    5
    11
    Muscle spasms
         subjects affected / exposed
    6 / 66 (9.09%)
    3 / 63 (4.76%)
    9 / 129 (6.98%)
         occurrences all number
    7
    3
    10
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    5 / 66 (7.58%)
    4 / 63 (6.35%)
    9 / 129 (6.98%)
         occurrences all number
    5
    4
    9
    Respiratory tract infection
         subjects affected / exposed
    5 / 66 (7.58%)
    2 / 63 (3.17%)
    7 / 129 (5.43%)
         occurrences all number
    5
    3
    8
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 66 (9.09%)
    8 / 63 (12.70%)
    14 / 129 (10.85%)
         occurrences all number
    6
    10
    16
    Urinary tract infection
         subjects affected / exposed
    6 / 66 (9.09%)
    3 / 63 (4.76%)
    9 / 129 (6.98%)
         occurrences all number
    6
    5
    11
    Metabolism and nutrition disorders
    Hypocalcaemia
         subjects affected / exposed
    3 / 66 (4.55%)
    4 / 63 (6.35%)
    7 / 129 (5.43%)
         occurrences all number
    3
    4
    7
    Hypokalaemia
         subjects affected / exposed
    3 / 66 (4.55%)
    3 / 63 (4.76%)
    6 / 129 (4.65%)
         occurrences all number
    4
    6
    10

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Jun 2016
    Amendment 1 was dated 28 June 2016 and included the following key changes: - Modified inclusion and exclusion criteria to clarify definition of the subject population - Prohibited use of doxycycline for 6 weeks before study entry and during the study (unless required for treatment of infection) - Clarified timing of 6-minute walk tests (6MWTs) and emphasized that two 6MWTs were required at Screening - Clarified management of suspected systemic infusion-related/hypersensitivity AEs - Extended the AE/serious adverse event (SAE) reporting period - Expanded description of safety analyses
    25 Apr 2017
    Amendment 2 was dated 25 April 2017 and included the following key changes: - Added new endpoints and modified existing endpoints; secondary and exploratory endpoints were modified following receipt of scientific advice on the statistical analysis plan (SAP) - Increased the number of subjects (from at least 100 to up to 130) - Removed a requirement for monthly collection of additional coagulation indices - Corrected Inclusion Criterion #7 to align with existing stratification factor - Updated analysis populations and statistical analyses to align with the SAP
    22 Oct 2017
    Amendment 3 was dated 22 October 2017 and included the following key changes: - Modified existing secondary and exploratory endpoints - Added NT-proBNP slope over 12 months of treatment as a secondary endpoint - Modified statistical section to align with updated secondary and exploratory endpoints

    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA