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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42312   clinical trials with a EudraCT protocol, of which   6968   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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 Single Arm, Prospective, Open-label, Multi-center Study to Evaluate Efficacy and Safety in Chinese Patients with Infantile-Onset Pompe Disease with One Year Alglucosidase Alfa Treatment

    Summary
    EudraCT number
    2021-004047-25
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    30 Dec 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    11 Sep 2021
    First version publication date
    11 Sep 2021
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    ALGMYL08718
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03687333
    WHO universal trial number (UTN)
    U1111-1203-8484
    Other trial identifiers
    Study Name: APOLLO-IOPD
    Sponsors
    Sponsor organisation name
    Genzyme, a Sanofi Company
    Sponsor organisation address
    50 Binney Street, Cambridge, Massachusetts, United States, 02142
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    22 Mar 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Dec 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate effect of 52-week treatment with Alglucosidase Alfa in the extension of survival and improvement of cardiomyopathy measured by Left Ventricular Mass Index (LVMI) in Chinese subjects with infantile-onset Pompe Disease (IOPD).
    Protection of trial subjects
    The study was conducted by investigators experienced in the treatment of paediatric patients. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimised. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia might have been used to minimise distress and discomfort.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    04 Dec 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    China: 10
    Worldwide total number of subjects
    10
    EEA total number of subjects
    0
    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)
    10
    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
    Study was conducted at 4 active study centres in China. A total of 12 subjects were screened between 04 Dec 2018 and 3 Dec 2019, of which 02 subjects failed screening mainly due to unmet inclusion criteria and/or met exclusion criteria and withdrawal of the informed consent by parents or legal guardians of subject, respectively.

    Pre-assignment
    Screening details
    A total of 10 subjects were treated in this study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Alglucosidase Alfa
    Arm description
    Subjects received Alglucosidase alfa, 20 milligrams per kilogram (mg/kg) body weight intravenous (IV) infusion every 2 weeks for up to 52 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Alglucosidase alfa
    Investigational medicinal product code
    Other name
    Myozyme®
    Pharmaceutical forms
    Powder for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Alglucosidase alfa 20 mg/kg body weight IV infusion every 2 weeks for 52 Weeks. Dose was allowed to be increased up to 40 mg/kg for subjects who showed sub-optimal response to the treatment.

    Number of subjects in period 1
    Alglucosidase Alfa
    Started
    10
    Completed
    9
    Not completed
    1
         Unspecified
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Alglucosidase Alfa
    Reporting group description
    Subjects received Alglucosidase alfa, 20 milligrams per kilogram (mg/kg) body weight intravenous (IV) infusion every 2 weeks for up to 52 weeks.

    Reporting group values
    Alglucosidase Alfa Total
    Number of subjects
    10 10
    Age categorical
    Units: Subjects
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    4.91 ± 1.607 -
    Gender categorical
    Units: Subjects
        Female
    6 6
        Male
    4 4

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Alglucosidase Alfa
    Reporting group description
    Subjects received Alglucosidase alfa, 20 milligrams per kilogram (mg/kg) body weight intravenous (IV) infusion every 2 weeks for up to 52 weeks.

    Primary: Percentage of Subjects Who Survived at Week 52

    Close Top of page
    End point title
    Percentage of Subjects Who Survived at Week 52 [1]
    End point description
    Binomial proportion and its 95% confidence interval were used to analyse the percentage of survivals. Analysis was performed on intent-to-treat (ITT) population which included all subjects treated with Alglucosidase alfa.
    End point type
    Primary
    End point timeframe
    At Week 52
    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: As the endpoint was descriptive in nature, no inferential statistical analysis was provided.
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    10
    Units: percentage of subjects
        number (confidence interval 95%)
    90.0 (55.5 to 99.7)
    No statistical analyses for this end point

    Primary: Change From Baseline in Left Ventricular Mass (LVM) Index at Week 52

    Close Top of page
    End point title
    Change From Baseline in Left Ventricular Mass (LVM) Index at Week 52 [2]
    End point description
    LVM were assessed by echocardiograms. LVM index was an index value derived by normalizing LVM by body surface area. LVM index provides evidence of cardiomyopathy. LVM index values less than (<) 65 gram per metre quare (g/m^2) were considered as normal and LVM index values greater than or equal to (>=) 65 g/m^2 were considered as abnormal. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline, Week 52
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint was descriptive in nature, no inferential statistical analysis was provided.
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    9
    Units: g/m^2
        arithmetic mean (standard deviation)
    -227.60 ± 155.991
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Invasive Ventilator Use-Free Survival at Week 52

    Close Top of page
    End point title
    Percentage of Subjects With Invasive Ventilator Use-Free Survival at Week 52
    End point description
    Invasive ventilator-free survival was defined as the time during which the subject was alive and not invasively ventilated. Binomial proportion and its 95% confidence interval were used to analyse the percentage of invasive ventilator use-free survival. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who did not use any invasive ventilator and were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    9
    Units: percentage of subjects
        number (confidence interval 95%)
    100 (66.4 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Any Ventilator Use-Free Survival at Week 52

    Close Top of page
    End point title
    Percentage of Subjects With Any Ventilator Use-Free Survival at Week 52
    End point description
    Ventilator-free survival was defined as the time during which the subject was alive and not ventilated. Binomial proportion and its 95% confidence interval were used to analyse the percentage of any ventilator use-free survival. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who did not use any ventilator and were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    8
    Units: percentage of subjects
        number (confidence interval 95%)
    100 (63.1 to 100)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Physical Growth at Week 52: Length

    Close Top of page
    End point title
    Change From Baseline in Physical Growth at Week 52: Length
    End point description
    Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    9
    Units: centimetre
        arithmetic mean (standard deviation)
    12.66 ± 4.676
    No statistical analyses for this end point

    Secondary: Change From Baseline in Physical Growth at Week 52: Weight

    Close Top of page
    End point title
    Change From Baseline in Physical Growth at Week 52: Weight
    End point description
    Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    9
    Units: kilogram
        arithmetic mean (standard deviation)
    2.69 ± 0.752
    No statistical analyses for this end point

    Secondary: Number of Motor Development Milestones Achieved at Week 52

    Close Top of page
    End point title
    Number of Motor Development Milestones Achieved at Week 52
    End point description
    Motor development was assessed by a 11-point scale ranged from 0 (worst motor behavior) to 11 (better motor behavior). A higher score means better motor behavior. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    9
    Units: score on a scale
        arithmetic mean (standard deviation)
    4.8 ± 1.99
    No statistical analyses for this end point

    Secondary: Change From Baseline in Motor Development Status at Week 52

    Close Top of page
    End point title
    Change From Baseline in Motor Development Status at Week 52
    End point description
    Motor development was assessed by a 11-point scale ranged from 0 (worst motor behavior) to 11 (better motor behavior). A higher score means better motor status. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    9
    Units: score on a scale
        arithmetic mean (standard deviation)
    3.9 ± 1.62
    No statistical analyses for this end point

    Secondary: Change From Baseline in GESELL Developmental Scale at Week 52

    Close Top of page
    End point title
    Change From Baseline in GESELL Developmental Scale at Week 52
    End point description
    GESELL developmental scale was used to assess motor development and functional independence of infants. The GESELL developmental scale measures: adaptive (cognitive) behavior, motor, language behavior, and personal-social behavior. Higher measured mature age represented higher developmental quotient, and higher developmental quotient represented better status. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    9
    Units: score on a scale
    arithmetic mean (standard deviation)
        Motor
    5.87 ± 3.68
        Adaptive (cognitive)
    8.50 ± 3.26
        Language
    6.82 ± 3.05
        Personal-social behavior
    8.73 ± 3.11
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Signs and/or Symptoms of Cardiac Failure at Week 52

    Close Top of page
    End point title
    Percentage of Subjects With Signs and/or Symptoms of Cardiac Failure at Week 52
    End point description
    Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    Alglucosidase Alfa
    Number of subjects analysed
    9
    Units: percentage of subjects
        number (not applicable)
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were collected from first dose of investigational medicinal product (IMP) up to 30 days after the last dose of IMP (Week 56).
    Adverse event reporting additional description
    Reported AEs were treatment-emergent AEs (TEAEs), that developed/worsened or became serious during during TEAE period (from first dose of IMP up to 30 days after last dose of IMP [Week 56]). Analysis was performed on safety population which included subjects who received at least 1 dose or part of a dose of IMP.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Alglucosidase Alfa
    Reporting group description
    Subjects received Alglucosidase alfa, 20 mg/kg body weight IV infusion every 2 weeks for up to 52 weeks.

    Serious adverse events
    Alglucosidase Alfa
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 10 (90.00%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    1
    Respiratory, thoracic and mediastinal disorders
    Pnenumonitis
         subjects affected / exposed
    6 / 10 (60.00%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Pnenumonia aspiration
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Choking
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Asphyxia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pnenumonia
         subjects affected / exposed
    3 / 10 (30.00%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Alglucosidase Alfa
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 10 (100.00%)
    Injury, poisoning and procedural complications
    Device use error
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Surgical and medical procedures
    Central venous catheterisation
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Investigations
    Respiratory rate decreased
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Heart rate decreased
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Pnenumonitis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Pnenumonia aspiration
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Ear and labyrinth disorders
    Eustachian tube dysfunction
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    3 / 10 (30.00%)
         occurrences all number
    3
    Aphthous ulcer
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Diarrhoea
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Dyspepsia
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Infantile spitting up
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Eczema
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 10 (30.00%)
         occurrences all number
    3
    Respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Otitis media
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    2
    Gastroenteritis
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2018
    Following changes were made: Adjustment of instruction of use of MYOZYME® for those subjects whose cross-reacting immunologic material (CRIM) was negative, revised to “CRIM status was rapidly inferred by gene mutation analysis, using an established mutation database.” Adjustment of assessment during treatment, revised to “blood sample was collected for CRIM status determination through genotyping at screening visit in each site, only if written results was not available.” On May 2021, following changes were made: Due to adenosine deaminase (ADA) test was not done in China, according to global medical suggestions to of removing the ADA related content. The Kaplan-Meier methodology and modified relevant description was removed due to not enough sample size for Kaplan-Meier methodology.

    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, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA