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   43884   clinical trials with a EudraCT protocol, of which   7296   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:
    An Open Label, Multicenter, Dose Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of SBC-102 in Children with Growth Failure Due to Lysosomal Acid Lipase Deficiency

    Summary
    EudraCT number
    2011-000032-28
    Trial protocol
    GB   FR   DE   IT   IE  
    Global end of trial date
    03 Jan 2018

    Results information
    Results version number
    v2(current)
    This version publication date
    15 Feb 2019
    First version publication date
    20 Jul 2016
    Other versions
    v1
    Version creation reason
    • New data added to full data set
    Results data updated with the data from the final clinical study report.

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    LAL-CL03
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01371825
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Alexion Pharmaceuticals Inc.
    Sponsor organisation address
    100 College Street, New Haven, CT, United States, 06510
    Public contact
    European Clinical Trial Information, Alexion Europe SAS, +33 147100606, clinicaltrials.eu@alexion.com
    Scientific contact
    European Clinical Trial Information, Alexion Europe SAS, +33 147100606, clinicaltrials.eu@alexion.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-001331-PIP01-12
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Jan 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Jan 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Jan 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to evaluate the effect of sebelipase alfa (SBC-102) therapy on survival at 12 months of age in children with growth failure due to lysosomal acid lipase (LAL) Deficiency.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted. The participant's parent or legal guardian had the right to withdraw from the study at any time for any reason. The investigator and Sponsor also had the right to withdraw participants from the study at any time. Specific reasons for discontinuation included but were not restricted to the following: - intercurrent illness - adverse events - protocol deviation or non-compliance - termination of the study by the sponsor
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    04 May 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    4 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Turkey: 1
    Country: Number of subjects enrolled
    Egypt: 1
    Country: Number of subjects enrolled
    United States: 1
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Ireland: 1
    Worldwide total number of subjects
    9
    EEA total number of subjects
    6
    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)
    9
    Children (2-11 years)
    0
    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
    A total of 9 Principal Investigators at 9 centers participated in this study in the United Kingdom, United States, France, Turkey, Ireland, and Egypt.

    Pre-assignment
    Screening details
    To assess eligibility, participants were screened for a period of up to 3 weeks prior to enrollment. 11 total participants were screened, and 2 participants died during screening. The other 9 participants, all of whom were ≤ 8 months of age on the date of enrollment, met all eligibility criteria and were enrolled, treated, and analysed.

    Period 1
    Period 1 title
    Open-label Sebelipase Alfa (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Open-Label Sebelipase Alfa
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Sebelipase alfa
    Investigational medicinal product code
    SBC-102
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    All participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment period. Participants received a starting dose of 0.35 milligrams (mg)/kilogram (kg) once weekly (qw) and, after demonstrating acceptable safety and tolerability after at least 2 infusions at this dose, began receiving the per-protocol dose of 1 mg/kg qw. Thereafter, participants were to continue receiving a dose of 1 mg/kg qw for the duration of the treatment period. However, in the event of disease progression (based on protocol-defined criteria) at any time during treatment with 1 mg/kg qw, an individual participant could receive a dose increase to 3 mg/kg qw and, if necessary, a subsequent dose increase to 5 mg/kg qw (after review and approval by a Safety Committee [SC]). Participants receiving long-term treatment on a stable qw dose could be switched to an every other week (qow) dosing schedule at the same total dose (mg/kg) per infusion.

    Number of subjects in period 1
    Open-Label Sebelipase Alfa
    Started
    9
    Received at Least 1 Dose of Study Drug
    9
    Completed
    5
    Not completed
    4
         Death
    4

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Open-label Sebelipase Alfa
    Reporting group description
    -

    Reporting group values
    Open-label Sebelipase Alfa Total
    Number of subjects
    9 9
    Age categorical
    Units: Subjects
        Infants and toddlers (28 days-23 months)
    9 9
    Age continuous
    The mean age (and range) at first dose of sebelipase alfa is presented.
    Units: months
        arithmetic mean (full range (min-max))
    3.41 (1.1 to 5.8) -
    Gender categorical
    Units: Subjects
        Female
    4 4
        Male
    5 5
    Race
    Units: Subjects
        White
    4 4
        Asian
    1 1
        Black
    1 1
        Unknown or not reported
    3 3
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    0 0
        Not Hispanic or Latino
    6 6
        Unknown or not reported
    3 3
    Subject analysis sets

    Subject analysis set title
    Primary Efficacy Analysis Set (PES)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Evaluable participants in the PES, which included participants who received any amount of sebelipase alfa and who were ≤ 8 months of age on the date of their first infusion of sebelipase alfa. All 9 participants were evaluable.

    Subject analysis sets values
    Primary Efficacy Analysis Set (PES)
    Number of subjects
    9
    Age categorical
    Units: Subjects
        Infants and toddlers (28 days-23 months)
    9
    Age continuous
    The mean age (and range) at first dose of sebelipase alfa is presented.
    Units: months
        arithmetic mean (full range (min-max))
    3.41 (1.1 to 5.8)
    Gender categorical
    Units: Subjects
        Female
    4
        Male
    5
    Race
    Units: Subjects
        White
    4
        Asian
    1
        Black
    1
        Unknown or not reported
    3
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    0
        Not Hispanic or Latino
    6
        Unknown or not reported
    3

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Open-Label Sebelipase Alfa
    Reporting group description
    -

    Subject analysis set title
    Primary Efficacy Analysis Set (PES)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Evaluable participants in the PES, which included participants who received any amount of sebelipase alfa and who were ≤ 8 months of age on the date of their first infusion of sebelipase alfa. All 9 participants were evaluable.

    Primary: Percentage Of Participants In The PES Surviving To 12 Months Of Age

    Close Top of page
    End point title
    Percentage Of Participants In The PES Surviving To 12 Months Of Age [1]
    End point description
    The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
    End point type
    Primary
    End point timeframe
    Month 12
    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: Single-arm estimate. The proportion of participants surviving to 12 months of age was calculated, along with an exact 95% confidence interval, based on the Clopper-Pearson method. Kaplan- Meier survival curves were also generated from birth to 12 months of age and from first infusion of sebelipase alfa to 12 months of age, and Kaplan-Meier methodology was used to estimate median age at death (as data permitted) and median survival past the first infusion of sebelipase alfa.
    End point values
    Primary Efficacy Analysis Set (PES)
    Number of subjects analysed
    9
    Units: % of subjects
        number (confidence interval 95%)
    67 (29.9 to 92.5)
    No statistical analyses for this end point

    Secondary: Percentage Of Participants Surviving Beyond 12 Months Of Age

    Close Top of page
    End point title
    Percentage Of Participants Surviving Beyond 12 Months Of Age
    End point description
    The percentage of participants in the PES who survived to at least 18 months of age.
    End point type
    Secondary
    End point timeframe
    From Baseline to Month 18, Month 24, Month 36, Month 48, and Month 60.
    End point values
    Primary Efficacy Analysis Set (PES)
    Number of subjects analysed
    9
    Units: % of subjects
    number (confidence interval 95%)
        Survival Through 18 Months of Age
    56 (21.2 to 86.3)
        Survival Through 24 Months of Age
    56 (21.2 to 86.3)
        Survival Through 36 Months of Age
    56 (21.2 to 86.3)
        Survival Through 48 Months of Age
    56 (21.2 to 86.3)
        Survival Through 60 Months of Age
    43 (9.9 to 81.6)
    No statistical analyses for this end point

    Secondary: Median Age At Death

    Close Top of page
    End point title
    Median Age At Death
    End point description
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 260
    End point values
    Primary Efficacy Analysis Set (PES)
    Number of subjects analysed
    4
    Units: age at death in months
        median (full range (min-max))
    3.63 (2.8 to 15.0)
    No statistical analyses for this end point

    Secondary: Change From Baseline To Months 12, 24, 36, 48, and 60 In Weight For Age (WFA) Percentiles

    Close Top of page
    End point title
    Change From Baseline To Months 12, 24, 36, 48, and 60 In Weight For Age (WFA) Percentiles
    End point description
    Baseline is defined as the last measurement prior to the first infusion of sebelipase alfa.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
    End point values
    Primary Efficacy Analysis Set (PES)
    Number of subjects analysed
    9
    Units: WFA Percentile
    median (full range (min-max))
        Month 12 (n=4)
    7.469 (5.35 to 13.77)
        Month 24 (n=5)
    21.787 (0.91 to 30.37)
        Month 36 (n=5)
    14.037 (-0.35 to 89.00)
        Month 48 (n=5)
    15.770 (4.06 to 86.50)
        Month 60 (n=5)
    19.869 (7.36 to 71.39)
    No statistical analyses for this end point

    Secondary: Number Of Participants With Stunting, Wasting, Or Underweight

    Close Top of page
    End point title
    Number Of Participants With Stunting, Wasting, Or Underweight
    End point description
    The number of participants who met criteria for the following dichotomous indicators of under nutrition were reported. These indicators included the following: • Stunting was defined as at least 2 standard deviations below the median for length-for-age/height-for-age; • Wasting was defined as wasting at least 2 standard deviations below the median for weight-for-length/weight-for-height; and • Underweight was defined as at least 2 standard deviations below the median for WFA.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60.
    End point values
    Primary Efficacy Analysis Set (PES)
    Number of subjects analysed
    9
    Units: number of participants
        Stunting at Baseline (N=8)
    4
        Stunting at Month 12 (N=4)
    1
        Stunting at Month 24 (N=5)
    0
        Stunting at Month 36 (N=5)
    0
        Stunting at Month 48 (N=5)
    0
        Stunting at Month 60 (N=5)
    0
        Wasting at Baseline (N=8)
    2
        Wasting at Month 12 (N=4)
    0
        Wasting at Month 24 (N=5)
    0
        Wasting at Month 36 (N=5)
    0
        Wasting at Month 48 (N=5)
    0
        Wasting at Month 60 (N=5)
    0
        Underweight at Baseline (N=9)
    2
        Underweight at Month 12 (N=4)
    0
        Underweight at Month 24 (N=5)
    1
        Underweight at Month 36 (N=5)
    0
        Underweight at Month 48 (N=5)
    0
        Underweight at Month 60 (N=5)
    0
        No Stunting/Wasting/Underweight at Baseline (N=9)
    4
        No Stunting/Wasting/Underweight at Month 12 (N=4)
    3
        No Stunting/Wasting/Underweight at Month 24 (N=5)
    4
        No Stunting/Wasting/Underweight at Month 36 (N=5)
    5
        No Stunting/Wasting/Underweight at Month 48 (N=5)
    5
        No Stunting/Wasting/Underweight at Month 60 (N=5)
    5
    No statistical analyses for this end point

    Secondary: Change From Baseline To Months 12, 24, 36, 48, and 60 In Serum Transaminases (ALT And AST)

    Close Top of page
    End point title
    Change From Baseline To Months 12, 24, 36, 48, and 60 In Serum Transaminases (ALT And AST)
    End point description
    Change from Baseline to Months 12, 24, 36, 48, and 60 for alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
    End point values
    Primary Efficacy Analysis Set (PES)
    Number of subjects analysed
    9
    Units: Median (units/Liter [U/L])
    median (full range (min-max))
        ALT, Month 12 (N=4)
    -13.50 (-121.00 to 12.00)
        ALT, Month 24 (N=5)
    -5.00 (-111.00 to 228.00)
        ALT, Month 36 (N=5)
    -4.00 (-100.00 to 107.00)
        ALT, Month 48 (N=4)
    -27.50 (-129.00 to -2.00)
        ALT, Month 60 (N=4)
    -27.00 (-122.00 to 2.00)
        AST, Month 12 (N=4)
    -43.50 (-62.00 to -29.00)
        AST, Month 24 (N=5)
    -30.00 (-49.00 to 67.00)
        AST, Month 36 (N=4)
    -33.00 (-49.00 to 86.00)
        AST, Month 48 (N=5)
    -51.00 (-67.00 to -31.00)
        AST, Month 60 (N=4)
    -40.00 (-84.00 to -17.00)
    No statistical analyses for this end point

    Secondary: Change From Baseline To Months 12, 24, 36, 48, and 60 In Serum Ferritin

    Close Top of page
    End point title
    Change From Baseline To Months 12, 24, 36, 48, and 60 In Serum Ferritin
    End point description
    The median change in serum ferritin from Baseline to Months 12, 24, 36, 48, and 60 is presented.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
    End point values
    Primary Efficacy Analysis Set (PES)
    Number of subjects analysed
    9
    Units: micrograms/Liter (µg/L)
    median (full range (min-max))
        Month 12 (N=3)
    -294.40 (-562.2 to -271.0)
        Month 24 (N=3)
    -239.00 (-298.0 to -235.0)
        Month 36 (N=4)
    -262.95 (-566.6 to -166.0)
        Month 48 (N=3)
    -268.00 (-278.0 to -179.0)
        Month 60 (N=3)
    -213.00 (-543.9 to -155.0)
    No statistical analyses for this end point

    Secondary: Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization (TFHN)

    Close Top of page
    End point title
    Number Of Participants Achieving And Maintaining Transfusion-free Hemoglobin Normalization (TFHN)
    End point description
    The number of participants achieving and maintaining TFHN are presented. For TFHN to be achieved, the participant must a) have had 2 post-baseline measurements of hemoglobin at least 4 weeks apart that were both above the age-adjusted lower limit of normal; b) have had no known additional measurements of hemoglobin that were below the age-adjusted lower limit of normal during the (minimum) 4-week period; and c) have had no transfusions during the (minimum) 4-week period, and also no transfusions for 2 weeks prior to the first hemoglobin measurement in the (minimum) 4-week period. For TFHN to be maintained, the participant must have been transfusion-free beginning at Week 6 and had all hemoglobin assessments above the lower limit of normal beginning in Week 8 and lasting at least 13 weeks.
    End point type
    Secondary
    End point timeframe
    Baseline to Month 60
    End point values
    Primary Efficacy Analysis Set (PES)
    Number of subjects analysed
    9
    Units: number of participants
        Achieved TFHN
    6
        Maintained TFHN
    2
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Week 260
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Open-Label sebelipase alfa
    Reporting group description
    -

    Serious adverse events
    Open-Label sebelipase alfa
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 9 (100.00%)
         number of deaths (all causes)
    4
         number of deaths resulting from adverse events
    Investigations
    Weight decreased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Pallor
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Poor venous access
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Tachycardia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Malabsorption
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Infections and infestations
    Bacterial pyelonephritis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Catheter site infection
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Roseola
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacteraemia
    Additional description: Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal toxaemia
    Additional description: staphylococcal sepsis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infection
    Additional description: Viral infection
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Adenovirus infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Amoebic dysentery
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Croup infectious
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rotavirus infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Failure to thrive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Food intolerance
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Acidosis
    Additional description: metabolic acidosis
         subjects affected / exposed
    1 / 9 (11.11%)
         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
    Open-Label sebelipase alfa
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 9 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Hypertension
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Pallor
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    5 / 9 (55.56%)
         occurrences all number
    69
    Chills
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    3
    Hyperthermia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Catheter site rash
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Disease progression
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Infusion Site Extravasation
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Feeling abnormal
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Gait disturbance
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Granuloma
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Infusion site oedema
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Irritability
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Pain
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Asthenia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Catheter site pain
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Catheter site swelling
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Swelling
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Reproductive system and breast disorders
    Penile blister
         subjects affected / exposed [1]
    1 / 5 (20.00%)
         occurrences all number
    1
    Genital rash
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 9 (55.56%)
         occurrences all number
    33
    Rhinorrhoea
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    14
    Pharyngeal erythema
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Respiratory failure
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Sneezing
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Tonsillar disorder
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Use of accessory respiratory muscles
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Wheezing
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Respiratory distress
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Productive cough
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Tachypnoea
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Tonsillar hypertrophy
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Irritability
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Emotional disorder
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Device malfunction
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Investigations
    Staphylococcus test positive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Blood immunoglobulin A abnormal
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Blood immunoglobulin G abnormal
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Blood potassium decreased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Blood urea increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Body temperature increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Lymphocyte count abnormal
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Lymphocyte count increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Monocyte count increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Neutrophil count increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Norovirus test positive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Platelet count increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Respiratory syncytial virus test positive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Serum ferritin increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Transaminases increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Urine albumin/creatinine ratio increased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Urine output decreased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Vitamin D decreased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Adenovirus test positive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Blood immunoglobulin G decreased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Blood albumin decreased
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    3
    Clostridium test positive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Parasite stool test positive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Pseudomonas test positive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Respirovirus test positive
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Vitamin E decreased
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Protein total decreased
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Endotracheal intubation complication
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Limb injury
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Mouth injury
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Post procedural discharge
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    3
    Postoperative ileus
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Fall
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Head injury
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Laceration
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Stoma site inflammation
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Tooth injury
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Congenital, familial and genetic disorders
    Hydrocele
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    5
    Bradycardia
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Cardiovascular disorder
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Nervous system disorders
    Hypotonia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Headache
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 9 (44.44%)
         occurrences all number
    6
    Thrombocytopenia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Lymphadenopathy
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Lymphopenia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    3
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    4
    Middle ear inflammation
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Pupillary disorder
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    6 / 9 (66.67%)
         occurrences all number
    53
    Diarrhoea
         subjects affected / exposed
    6 / 9 (66.67%)
         occurrences all number
    55
    Abdominal distension
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    5
    Nausea
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Teething
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    4
    Ascites
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Faeces discoloured
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Haematochezia
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    3
    Post-tussive vomiting
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    3
    Retching
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Tongue discolouration
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Umbilical hernia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Abdominal discomfort
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Abdominal pain
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    4
    Constipation
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Dental caries
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Enteritis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Flatulence
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Gastritis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Dermatitis diaper
         subjects affected / exposed
    4 / 9 (44.44%)
         occurrences all number
    7
    Urticaria
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    10
    Rash
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    10
    Eczema
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    3
    Pruritus generalised
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Umbilical erythema
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Petechiae
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Pruritus
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Rash macular
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Skin discolouration
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Skin irritation
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Xanthoma
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Erythema
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Infections and infestations
    Rhinitis
         subjects affected / exposed
    5 / 9 (55.56%)
         occurrences all number
    36
    Catheter site infection
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Device related infection
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    4
    Nasopharyngitis
         subjects affected / exposed
    5 / 9 (55.56%)
         occurrences all number
    14
    Ear infection viral
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    3
    Bronchiolitis
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Gastroenteritis
         subjects affected / exposed
    4 / 9 (44.44%)
         occurrences all number
    11
    Pharyngitis
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    6
    Varicella
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    3
    Bacterial infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Candida nappy rash
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Eyelid infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Fungal infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Metapneumovirus infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Oral candidiasis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Oral fungal infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Oral herpes
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Otitis media
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Post procedural infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Rash pustular
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Staphylococcal skin infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Viral infection
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    5
    Angular cheilitis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Croup infectious
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Gastroenteritis viral
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Infectious mononucleosis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Scarlet fever
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Stoma site candida
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Tonsillitis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Conjunctivitis
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Fungal skin infection
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Hand-foot-and-mouth disease
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Urinary tract infection
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Ear infection
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    4
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    5
    Dehydration
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Hypercalcaemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Hypernatraemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Hypocalcaemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Hypophosphataemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Hypoproteinaemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    2
    Iron deficiency
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Metabolic acidosis
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Vitamin D deficiency
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences all number
    4
    Hypovolaemia
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Vitamin A deficiency
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences all number
    1
    Vitamin E deficiency
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    2
    Vitamin K deficiency
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences all number
    5
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This adverse event only affects male participants.

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Feb 2011
    This amendment included the following major changes: • The system for grading adverse event (AE) severity was changed from Division of Acquired Immunodeficiency Syndrome to NCI CTCAE based on a regulatory request. • Addition of rules for stopping dosing in an individual participant or all study participants.
    20 May 2011
    All changes in country-specific Protocol Amendment 2 were incorporated in this global amendment, with one clarification (see first bullet below). This amendment included the following major changes: • Further clarified the first criterion in the definition of growth failure. • Amended the definition of extreme prematurity from < 32 weeks gestational age at birth to < 36 weeks gestational age at birth. • Added birth weight to the list of demographic information to be collected. • Allowed the dose (mg) of sebelipase alfa to be determined based on a participant's last available weight measurement if weight could not be obtained on the day of the infusion due to the participant's condition. • Allowed for a screening period of < 7 days, to minimise the delay in treatment initiation, which could be important for severe cases. • Allowed for replacement of participants who had received fewer than 4 infusions of sebelipase alfa.
    20 Sep 2011
    This global amendment included the following: • Clarifications to safety reporting guidelines made to comply with local regulations. • Nonclinical and clinical information for sebelipase alfa was also updated.
    05 Apr 2012
    This amendment merged study LAL-CL03 with its extension study, LAL-CL05, under a single protocol. Study LAL-CL03 was originally designed as a safety trial with a limited 4-month treatment period. After additional nonclinical chronic toxicology data and extended clinical experience in adults became available, the Sponsor opened LAL-CL05 as an extension study, to permit participants who had been receiving treatment in LAL-CL03 (or under an expanded access program) to continue receiving sebelipase alfa without interruption, and to evaluate the long-term safety and efficacy of sebelipase alfa in these participants, including an analysis of survival. In addition, all changes in country-specific Protocol Amendment 4 and Protocol Amendment 5 were incorporated in this global amendment.
    23 Oct 2012
    This amendment included the following major changes: • Added the option of a qow dosing schedule for participants who were on treatment for at least 96 weeks and had been on a stable dose for at least 24 weeks. • Modified the definition of suboptimal response to distinguish between early (first 3 months of treatment) and late (beyond 3 months of treatment) suboptimal response -- and added criteria for late suboptimal response. • Added anti-drug antibody (ADA) and tryptase testing in participants who experienced a moderate or severe infusion associated reaction (IAR). • Clarified that continuation of hospitalisation for trial purposes in participants who were already hospitalised at the start of the study due to severity of disease, would not be considered a serious adverse event (SAE).
    05 Feb 2013
    This amendment was written to allow enrollment of a participant who had not yet met the criteria for growth failure if (a) the investigator has substantial clinical concerns based on evidence of the rapid disease progression requiring urgent medical intervention and (b) the participant had an older (biological) sibling who had a documented rapidly progressive course of LAL Deficiency with growth failure before 6 months of age. This exception was included as a footnote to the growth failure inclusion criterion, and further specified the process the Investigator was to follow to obtain approval for enrollment of such a participant.
    19 Mar 2013
    This amendment included the following major change: • Modified the language introduced in Amendment 8. Specifically, the footnote to the growth failure inclusion criterion was revised to remove the requirement that the participant have an older (biological) sibling who had a documented rapidly progressive course of LAL Deficiency with growth failure before 6 months of age.
    24 Jan 2014
    This amendment included the following major changes: • Extended the treatment period for each participant up to maximum of 4 years. • Refined the definition of suboptimal response, and specified that the evaluation of the suboptimal response was done in consultation with the SC. • Added an optional dose increase to 5 mg/kg qw for any participant who had a continued suboptimal response at 3 mg/kg (after at least 4 infusions) in association with the presence of neutralising antibodies. • Added annual magnetic resonance imaging, monthly weights after Week 24, and an optional liver biopsy.
    21 Nov 2014
    This amendment included the following changes: • Extended dosing period to up to 5 years. • Removed the terminology “suboptimal response” and replaced with criteria for dose escalation. • Added the collection of serum lipid, serum liver, hematology, chemistry, ferritin, and high-sensitivity C-reactive protein labs prior to any dose change and serum lipid and serum liver 4, 8, and 12 weeks following any dose change. • Removed the terminology “total and functional area scores” relating to the Denver II. • Modified safety end points characterizing ADAs to remove reference to immunoglobulin G, seroconversion, and tolerization. • Removed infusion duration time, infusion rate table, and added in the final concentration of the infusion. •Antidrug antibody collection time points were updated from every 24 weeks following Week 24 to every 12 weeks following Week 24. •Revised the text on infusion associated reaction (IAR) management. •Revised the stopping rules to remove stopping rule for an individual participant for grade 1 and 2 IARs, for grade 4 AEs. •Removed specific stopping rule to pause dosing in all participants in the case of 3 or more participants with similar SAEs and in 3 or more participants with recurrent, unmanageable severe or higher IARs.
    05 Jan 2016
    This amendment included the following minor changes: • Updated to the Sponsor information and SAE Reporting information (updated where to report SAEs, such as phone numbers)

    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