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   43865   clinical trials with a EudraCT protocol, of which   7286   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 3 Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 2 Through 5 Years of Age

    Summary
    EudraCT number
    		 2020-002251-38
    Trial protocol
    		 DE  
    Global end of trial date
    03 Jun 2022

    Results information
    Results version number
    		 v1
    This version publication date
    17 Dec 2022
    First version publication date
    17 Dec 2022
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    VX20-445-111
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04537793
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND Number: 132547
    Sponsors
    Sponsor organisation name
    Vertex Pharmaceuticals Incorporated
    Sponsor organisation address
    50 Northern Avenue, Boston, Massachusetts, United States,
    Public contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
    Scientific contact
    Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002324-PIP01-17
    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
    21 Jun 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Jun 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Jun 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination therapy in cystic fibrosis (CF) subjects 2 through 5 years of age.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Nov 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 49
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    Canada: 11
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    Germany: 7
    Worldwide total number of subjects
    83
    EEA total number of subjects
    7
    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)
    83
    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
    		 -

    Pre-assignment
    Screening details
    		 This study was conducted in subjects with CF aged 2 through 5 years of age (inclusive).

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Part A: ELX/TEZ/IVA
    Arm description
    		 Subjects received ELX/TEZ/IVA in the morning and IVA in the evening based on their weight at Day 1 for 15 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ELX/TEZ/IVA
    Investigational medicinal product code
    VX-445/VX-661/VX-770
    Other name
    Elexacaftor/Tezacaftor/Ivacaftor
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received ELX/TEZ/IVA fixed-dose combination once daily in the morning.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA once daily in the evening.

    Arm title
    		 Part B: ELX/TEZ/IVA
    Arm description
    		 Subjects received ELX/TEZ/IVA in the morning and IVA in the evening based on their weight at Day 1 for 24 Weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ELX/TEZ/IVA
    Investigational medicinal product code
    VX-445/VX-661/VX-770
    Other name
    Elexacaftor/Tezacaftor/Ivacaftor
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received ELX/TEZ/IVA fixed-dose combination once daily in the morning.

    Investigational medicinal product name
    IVA
    Investigational medicinal product code
    VX-770
    Other name
    Ivacaftor
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received IVA once daily in the evening.

    Number of subjects in period 1
    		Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
    Started
    18
    75
    Completed
    18
    74
    Not completed
    0
    1
         Adverse event
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Part A: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX/TEZ/IVA in the morning and IVA in the evening based on their weight at Day 1 for 15 days.

    Reporting group title
    Part B: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX/TEZ/IVA in the morning and IVA in the evening based on their weight at Day 1 for 24 Weeks.

    Reporting group values
    		 Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA Total
    Number of subjects
    		 18 75 83
    Age categorical
    There were 83 unique subjects enrolled in the study. Out of 18 subjects from Part A, 10 subjects also participated in Part B.
    Units: Subjects
        Children (2-11 years)
    		 18 75 83
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 4.3 ± 0.8 4.1 ± 1.1 -
    Gender categorical
    There were 83 unique subjects enrolled in the study. Out of 18 subjects from Part A, 10 subjects also participated in Part B. The total column for gender represents the sum of Part A and Part B numbers as the data for unique 83 subjects was not collected separately.
    Units: Subjects
        Female
    		 11 41 52
        Male
    		 7 34 41

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Part A: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX/TEZ/IVA in the morning and IVA in the evening based on their weight at Day 1 for 15 days.

    Reporting group title
    Part B: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX/TEZ/IVA in the morning and IVA in the evening based on their weight at Day 1 for 24 Weeks.

    Primary: Part A: Observed pre-dose concentration (Ctrough) of ELX, TEZ, IVA, and relevant metabolites

    		 Close Top of page
    End point title
    		 Part A: Observed pre-dose concentration (Ctrough) of ELX, TEZ, IVA, and relevant metabolites [1] [2]
    End point description
    PK set included subjects who received at least 1 dose of study drug. Here “n” signifies those subjects who were evaluable at specified time points for each reporting group respectively.
    End point type
    Primary
    End point timeframe
    From Day 1 through Day 15
    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: Only descriptive statistics were planned. No statistical comparisons were planned for this endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This primary endpoint is only applicable for Part A.
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    18
    Units: micrograms per milliliter (µg/ml)
    arithmetic mean (standard deviation)
        Day 1: ELX (n= 18)
    0.00 ± 0.00
        Day 8: ELX (n= 18)
    3.44 ± 2.09
        Day 15: ELX (n= 17)
    3.69 ± 2.11
        Day 1: ELX-M23 (n= 18)
    0.00 ± 0.00
        Day 8: ELX-M23 (n= 18)
    2.39 ± 1.65
        Day 15: ELX-M23 (n= 17)
    2.47 ± 1.65
        Day 1: IVA (n= 18)
    0.00 ± 0.00
        Day 8: IVA (n= 18)
    0.702 ± 0.503
        Day 15: IVA (n= 17)
    0.746 ± 0.526
        Day 1: IVA-M1 (n= 18)
    0.00 ± 0.00
        Day 8: IVA-M1 (n= 18)
    1.78 ± 0.990
        Day 15: IVA-M1 (n= 17)
    1.91 ± 0.990
        Day 1: TEZ (n= 18)
    0.00 ± 0.00
        Day 8: TEZ (n= 18)
    1.86 ± 1.07
        Day 15: TEZ (n= 17)
    1.85 ± 1.10
        Day 1: TEZ-M1 (n= 18)
    0.00 ± 0.00
        Day 8: TEZ-M1 (n= 18)
    6.42 ± 1.42
        Day 15: TEZ-M1 (n= 17)
    7.68 ± 1.52
    No statistical analyses for this end point

    Primary: Part A : Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent Adverse

    		 Close Top of page
    End point title
    		 Part A : Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent Adverse [3] [4]
    End point description
    Safety set included all subjects who received at least 1 dose of study drug in the treatment period.
    End point type
    Primary
    End point timeframe
    From Day 1 up to Day 43
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned. No statistical comparisons were planned for this endpoint.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This primary endpoint is only applicable for Part A.
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    18
    Units: Subjects
        Subjects with TEAEs
    15
        Subjects with SAEs
    0
    No statistical analyses for this end point

    Primary: Part B : Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent

    		 Close Top of page
    End point title
    		 Part B : Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent [5] [6]
    End point description
    Safety set included all subjects who received at least 1 dose of study drug in the treatment period.
    End point type
    Primary
    End point timeframe
    From Day 1 up to Week 28
    Notes
    [5] - 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: Only descriptive statistics were planned. No statistical comparisons were planned for this endpoint.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This primary endpoint is only applicable for Part B.
    End point values
    		 Part B: ELX/TEZ/IVA
    Number of subjects analysed
    75
    Units: Subjects
        Subjects with TEAEs
    74
        Subjects with SAEs
    2
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 Through Safety Follow-up Period (up to Day 43 for Part A and up to Week 28 for Part B)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Part A: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX/TEZ/IVA in the morning and IVA in the evening based on their weight at Day 1 for 15 days.

    Reporting group title
    Part B: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX/TEZ/IVA in the morning and IVA in the evening based on their weight at Day 1 for 24 Weeks.

    Serious adverse events
    		 Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 18 (0.00%)
    2 / 75 (2.67%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Gastrointestinal disorders
    Anal incontinence
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary incontinence
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 18 (0.00%)
    1 / 75 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 18 (83.33%)
    71 / 75 (94.67%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 18 (16.67%)
    8 / 75 (10.67%)
         occurrences all number
    3
    9
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 18 (11.11%)
    4 / 75 (5.33%)
         occurrences all number
    2
    7
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 18 (5.56%)
    4 / 75 (5.33%)
         occurrences all number
    1
    4
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 18 (0.00%)
    7 / 75 (9.33%)
         occurrences all number
    0
    7
    Injury, poisoning and procedural complications
    Scratch
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 75 (0.00%)
         occurrences all number
    1
    0
    Skin abrasion
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 75 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 18 (0.00%)
    7 / 75 (9.33%)
         occurrences all number
    0
    7
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 18 (5.56%)
    26 / 75 (34.67%)
         occurrences all number
    1
    33
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 18 (0.00%)
    5 / 75 (6.67%)
         occurrences all number
    0
    6
    Abdominal pain
         subjects affected / exposed
    1 / 18 (5.56%)
    4 / 75 (5.33%)
         occurrences all number
    1
    4
    Constipation
         subjects affected / exposed
    1 / 18 (5.56%)
    6 / 75 (8.00%)
         occurrences all number
    1
    6
    Vomiting
         subjects affected / exposed
    0 / 18 (0.00%)
    21 / 75 (28.00%)
         occurrences all number
    0
    25
    Diarrhoea
         subjects affected / exposed
    0 / 18 (0.00%)
    5 / 75 (6.67%)
         occurrences all number
    0
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 18 (22.22%)
    46 / 75 (61.33%)
         occurrences all number
    4
    84
    Nasal congestion
         subjects affected / exposed
    0 / 18 (0.00%)
    13 / 75 (17.33%)
         occurrences all number
    0
    18
    Productive cough
         subjects affected / exposed
    1 / 18 (5.56%)
    3 / 75 (4.00%)
         occurrences all number
    1
    3
    Rhinorrhoea
         subjects affected / exposed
    3 / 18 (16.67%)
    25 / 75 (33.33%)
         occurrences all number
    4
    34
    Sputum increased
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 75 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Papule
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 75 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 75 (1.33%)
         occurrences all number
    1
    1
    Rash
         subjects affected / exposed
    2 / 18 (11.11%)
    12 / 75 (16.00%)
         occurrences all number
    4
    14
    Rash erythematous
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 75 (1.33%)
         occurrences all number
    1
    1
    Urticaria
         subjects affected / exposed
    1 / 18 (5.56%)
    1 / 75 (1.33%)
         occurrences all number
    1
    1
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    0 / 18 (0.00%)
    4 / 75 (5.33%)
         occurrences all number
    0
    4
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 18 (0.00%)
    14 / 75 (18.67%)
         occurrences all number
    0
    14
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    0 / 18 (0.00%)
    8 / 75 (10.67%)
         occurrences all number
    0
    8
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 18 (5.56%)
    11 / 75 (14.67%)
         occurrences all number
    1
    13
    Nasopharyngitis
         subjects affected / exposed
    0 / 18 (0.00%)
    6 / 75 (8.00%)
         occurrences all number
    0
    13
    Product issues
    Product taste abnormal
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 75 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 18 (0.00%)
    9 / 75 (12.00%)
         occurrences all number
    0
    9
    Hyperamylasaemia
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 75 (0.00%)
         occurrences all number
    1
    0
    Hyperlipasaemia
         subjects affected / exposed
    1 / 18 (5.56%)
    0 / 75 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jun 2021
    Updated the dose in Part B; Updated the sample size for subjects between 2 and 3 years of age (inclusive) in Part B; Added guidance for blood draws; Updated exclusion criterion to avoid enrolling subjects with liver function test (LFT) abnormalities in the previous year in the study.
    21 Oct 2021
    Amended to expand the study population to include subjects who have at least 1 F508del mutation in the CFTR gene or an ELX/TEZ/IVA-responsive CFTR mutation in part B.

    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-Sun Apr 28 10:48:39 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA