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    Clinical Trial Results:
    A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

    Summary
    EudraCT number
    		 2019-000833-37
    Trial protocol
    		 DE   GB   IE   DK   FR   BE   ES   NL   IT  
    Global end of trial date
    16 Dec 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    02 Feb 2024
    First version publication date
    01 Jul 2023
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Addition of secondary end points to maintain consistency with CT.gov.

    Trial information

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    Trial identification
    Sponsor protocol code
    VX18-445-110
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04058366
    WHO universal trial number (UTN)
    		 -
    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)
    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
    09 Feb 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Dec 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Dec 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the long-term safety and tolerability of VX-445/tezacaftor (TEZ)/ivacaftor (IVA) in subjects with cystic fibrosis who are heterozygous for the F508del mutation and a gating (F/G) or residual function (F/RF) mutation.
    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
    05 Dec 2019
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 34 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 14
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    United Kingdom: 20
    Country: Number of subjects enrolled
    Belgium: 13
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    France: 27
    Country: Number of subjects enrolled
    Germany: 14
    Country: Number of subjects enrolled
    Ireland: 10
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    United States: 81
    Country: Number of subjects enrolled
    Australia: 26
    Country: Number of subjects enrolled
    Canada: 12
    Worldwide total number of subjects
    251
    EEA total number of subjects
    112
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    22
    Adults (18-64 years)
    224
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Subjects from parent study VX18-445-104 (NCT04058353) were enrolled in this study. A total of 251 subjects were enrolled in this study.

    Period 1
    Period 1 title
    Part A
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Part A: ELX/TEZ/IVA
    Arm description
    		 Subjects received ELX (elexacaftor) 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 96 weeks.
    Arm type
    		 Experimental

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

    Investigational medicinal product name
    Ivacaftor
    Investigational medicinal product code
    VX-770
    Other name
    IVA
    Pharmaceutical forms
    Tablet
    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
    Started
    251
    Completed
    215
    Not completed
    36
         Commercial drug is available for subjects
    6
         Other
    6
         Death
    1
         Adverse event
    14
         Other non-compliance
    2
         Withdrawal of Consent (not due to AE)
    7
    Period 2
    Period 2 title
    Part B
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Part B: ELX/TEZ/IVA
    Arm description
    		 Subjects received ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 48 weeks.
    Arm type
    		 Experimental

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

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

    Number of subjects in period 2 [1]
    		Part B: ELX/TEZ/IVA
    Started
    84
    Completed
    1
    Not completed
    83
         Commercial drug is available for subjects
    81
         Physician decision
    1
         Withdrawal of Consent (not due to AE)
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: A total 251 subjects were enrolled from the parent study on Part A. However, only 84 subjects rolled over to Part B from Part A of the study.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part A
    Reporting group description
    		 Subjects received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 96 weeks.

    Reporting group values
    		 Part A Total
    Number of subjects
    		 251 251
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 37.9 ± 14.4 -
    Gender categorical
    Units: Subjects
        Female
    		 124 124
        Male
    		 127 127
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 9 9
        Not Hispanic or Latino
    		 224 224
        Not collected per local regulations
    		 18 18
    Race
    Units: Subjects
        White
    		 225 225
        Black or African American
    		 2 2
        Other
    		 5 5
        Not collected per local regulations
    		 18 18
        More than one race
    		 1 1

    End points

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    End points reporting groups
    Reporting group title
    Part A: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX (elexacaftor) 200 milligram (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the treatment period for 96 weeks.
    Reporting group title
    Part B: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 48 weeks.

    Primary: Part A : Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Part A : Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [1]
    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 Baseline up to Week 100
    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 the Part A primary safety endpoint.
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    251
    Units: Subjects
        Subjects with TEAEs
    241
        Subjects with SAEs
    38
    No statistical analyses for this end point

    Primary: Part B: Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Part B: Safety and Tolerability as Assessed by Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [2]
    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 Baseline up to 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: Only descriptive statistics were planned. No statistical comparisons were planned for the Part B primary safety endpoint.
    End point values
    		 Part B: ELX/TEZ/IVA
    Number of subjects analysed
    84
    Units: Subjects
        Subjects with TEAEs
    62
        Subjects with SAEs
    3
    No statistical analyses for this end point

    Secondary: Part A: Absolute Change from Parent Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

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    End point title
    		 Part A: Absolute Change from Parent Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
    End point description
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The OL Full Analysis Set (OL-FAS) for Part A is defined as all enrolled subjects who have received at least 1 dose of study drug in the open-label study. This analysis set included study 104 parent study subjects who received Control IVA or TEZ/IVA and ELX/TEZ/IVA. Here "n" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 96
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    176
    Units: percentage points
    least squares mean (confidence interval 95%)
        Control-IVA or TEZ/IVA: Change at Week 96 (n=80)
    4.1 (2.5 to 5.7)
        ELX/TEZ/IVA: Change at Week 96 (n=96)
    3.7 (2.2 to 5.2)
    No statistical analyses for this end point

    Secondary: Part A: Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl)

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    End point title
    		 Part A: Absolute Change From Parent Study Baseline in Sweat Chloride (SwCl)
    End point description
    Sweat samples were collected using an approved collection device. The OL Full Analysis Set (OL-FAS) for Part A is defined as all enrolled subjects who have received at least 1 dose of study drug in the open-label study. This analysis set included study 104 parent study subjects who received Control IVA or TEZ/IVA and ELX/TEZ/IVA. Here, "n signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 96
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    186
    Units: millimole per liter (mmol/L)
    least squares mean (confidence interval 95%)
        Control-IVA or TEZ/IVA: Change at Week 96 (n=90)
    -23.0 (-25.8 to -20.1)
        ELX/TEZ/IVA: Change at Week 96 (n=96)
    -22.6 (-25.4 to -19.9)
    No statistical analyses for this end point

    Secondary: Part A: Absolute Change From Parent Study Baseline in Body Mass Index (BMI)

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    End point title
    		 Part A: Absolute Change From Parent Study Baseline in Body Mass Index (BMI)
    End point description
    BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).The OL Full Analysis Set (OL-FAS) for Part A is defined as all enrolled subjects who have received at least 1 dose of study drug in the open-label study. This analysis set included study 104 parent study subjects who received Control IVA or TEZ/IVA and ELX/TEZ/IVA. Here, "n" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 96
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    207
    Units: kg/m^2
    least squares mean (confidence interval 95%)
        Control-IVA or TEZ/IVA: Change at Week 96 (n=97)
    1.15 (0.84 to 1.45)
        ELX/TEZ/IVA: Change at Week 96 (n=110)
    0.83 (0.54 to 1.11)
    No statistical analyses for this end point

    Secondary: Part A: Absolute Change From Parent Study Baseline in BMI Z-score

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    End point title
    		 Part A: Absolute Change From Parent Study Baseline in BMI Z-score
    End point description
    BMI was defined as weight in kilogram (kg) divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The OL Full Analysis Set (OL-FAS) for Part A is defined as all enrolled subjects who have received at least 1 dose of study drug in the open-label study. This analysis set included study 104 parent study subjects who received Control IVA or TEZ/IVA and ELX/TEZ/IVA. Here, "n" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 96
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    18
    Units: z-score
    least squares mean (confidence interval 95%)
        Control-IVA or TEZ/IVA: Change at Week 96 (n=7)
    0.11 (-0.17 to 0.40)
        ELX/TEZ/IVA: Change at Week 96 (n=11)
    0.40 (0.17 to 0.62)
    No statistical analyses for this end point

    Secondary: Part A: Absolute Change From Parent Study Baseline in Body Weight

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    End point title
    		 Part A: Absolute Change From Parent Study Baseline in Body Weight
    End point description
    The OL Full Analysis Set (OL-FAS) for Part A is defined as all enrolled subjects who have received at least 1 dose of study drug in the open-label study. This analysis set included study 104 parent study subjects who received Control IVA or TEZ/IVA and ELX/TEZ/IVA. Here, "Number Analyzed" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 96
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    207
    Units: Kilogram (Kg)
    least squares mean (confidence interval 95%)
        Control-IVA or TEZ/IVA: Change at Week 96 (n=97)
    3.6 (2.7 to 4.6)
        ELX/TEZ/IVA: Change at Week 96 (n=110)
    2.9 (2.0 to 3.8)
    No statistical analyses for this end point

    Secondary: Part A: Absolute Change From Parent Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score

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    End point title
    		 Part A: Absolute Change From Parent Study Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
    End point description
    The CFQ-R is a validated subject-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. The OL Full Analysis Set (OL-FAS) for Part A is defined as all enrolled subjects who have received at least 1 dose of study drug in the open-label study. This analysis set included study 104 parent study subjects who received Control IVA or TEZ/IVA and ELX/TEZ/IVA. Here, "n" signifies subjects who were evaluable for the specified category.
    End point type
    Secondary
    End point timeframe
    From Baseline at Week 96
    End point values
    		 Part A: ELX/TEZ/IVA
    Number of subjects analysed
    208
    Units: units on a scale
    least squares mean (confidence interval 95%)
        Control-IVA or TEZ/IVA: Change at Week 96 (n=97)
    7.2 (4.1 to 10.4)
        ELX/TEZ/IVA: Change at Week 96 (n=111)
    8.1 (5.1 to 11.1)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 through Safety follow-up (up to Week 100 for Part A and up to Week 52 for Part B)
    Adverse event reporting additional description
    MedDRA 24.1 for Part A and MedDRA 25.1 for Part B
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1, 25.1
    Reporting groups
    Reporting group title
    Part A: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 96 weeks.

    Reporting group title
    Part B: ELX/TEZ/IVA
    Reporting group description
    		 Subjects received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 48 weeks.

    Serious adverse events
    		 Part A: ELX/TEZ/IVA Part B: ELX/TEZ/IVA
    Total subjects affected by serious adverse events
         subjects affected / exposed
    38 / 251 (15.14%)
    3 / 84 (3.57%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 251 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Epididymal cyst
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis
         subjects affected / exposed
    3 / 251 (1.20%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    2 / 251 (0.80%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 251 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Tendon rupture
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Hypoaesthesia
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastritis
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 251 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 251 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash erythematous
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    2 / 251 (0.80%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Aspergilloma
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    2 / 251 (0.80%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    16 / 251 (6.37%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 251 (0.40%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         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
    223 / 251 (88.84%)
    48 / 84 (57.14%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    16 / 251 (6.37%)
    0 / 84 (0.00%)
         occurrences all number
    25
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    16 / 251 (6.37%)
    0 / 84 (0.00%)
         occurrences all number
    23
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    26 / 251 (10.36%)
    1 / 84 (1.19%)
         occurrences all number
    26
    1
    Injury, poisoning and procedural complications
    Vaccination complication
         subjects affected / exposed
    28 / 251 (11.16%)
    0 / 84 (0.00%)
         occurrences all number
    46
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    71 / 251 (28.29%)
    4 / 84 (4.76%)
         occurrences all number
    188
    6
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    36 / 251 (14.34%)
    2 / 84 (2.38%)
         occurrences all number
    43
    2
    Fatigue
         subjects affected / exposed
    40 / 251 (15.94%)
    0 / 84 (0.00%)
         occurrences all number
    52
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    13 / 251 (5.18%)
    2 / 84 (2.38%)
         occurrences all number
    15
    4
    Constipation
         subjects affected / exposed
    17 / 251 (6.77%)
    1 / 84 (1.19%)
         occurrences all number
    26
    1
    Diarrhoea
         subjects affected / exposed
    48 / 251 (19.12%)
    4 / 84 (4.76%)
         occurrences all number
    74
    6
    Nausea
         subjects affected / exposed
    28 / 251 (11.16%)
    2 / 84 (2.38%)
         occurrences all number
    83
    8
    Gastrooesophageal reflux disease
         subjects affected / exposed
    13 / 251 (5.18%)
    1 / 84 (1.19%)
         occurrences all number
    15
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    65 / 251 (25.90%)
    5 / 84 (5.95%)
         occurrences all number
    96
    5
    Haemoptysis
         subjects affected / exposed
    20 / 251 (7.97%)
    5 / 84 (5.95%)
         occurrences all number
    44
    9
    Dyspnoea
         subjects affected / exposed
    29 / 251 (11.55%)
    2 / 84 (2.38%)
         occurrences all number
    38
    2
    Oropharyngeal pain
         subjects affected / exposed
    42 / 251 (16.73%)
    5 / 84 (5.95%)
         occurrences all number
    56
    6
    Nasal congestion
         subjects affected / exposed
    18 / 251 (7.17%)
    1 / 84 (1.19%)
         occurrences all number
    22
    1
    Sinus congestion
         subjects affected / exposed
    15 / 251 (5.98%)
    0 / 84 (0.00%)
         occurrences all number
    23
    0
    Rhinorrhoea
         subjects affected / exposed
    19 / 251 (7.57%)
    0 / 84 (0.00%)
         occurrences all number
    20
    0
    Productive cough
         subjects affected / exposed
    17 / 251 (6.77%)
    1 / 84 (1.19%)
         occurrences all number
    21
    1
    Sputum increased
         subjects affected / exposed
    34 / 251 (13.55%)
    3 / 84 (3.57%)
         occurrences all number
    58
    4
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    19 / 251 (7.57%)
    0 / 84 (0.00%)
         occurrences all number
    22
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    15 / 251 (5.98%)
    2 / 84 (2.38%)
         occurrences all number
    29
    4
    Anxiety
         subjects affected / exposed
    28 / 251 (11.16%)
    1 / 84 (1.19%)
         occurrences all number
    31
    1
    Depression
         subjects affected / exposed
    16 / 251 (6.37%)
    0 / 84 (0.00%)
         occurrences all number
    17
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    27 / 251 (10.76%)
    2 / 84 (2.38%)
         occurrences all number
    33
    2
    Back pain
         subjects affected / exposed
    20 / 251 (7.97%)
    2 / 84 (2.38%)
         occurrences all number
    20
    2
    Myalgia
         subjects affected / exposed
    16 / 251 (6.37%)
    1 / 84 (1.19%)
         occurrences all number
    23
    1
    Pain in extremity
         subjects affected / exposed
    13 / 251 (5.18%)
    0 / 84 (0.00%)
         occurrences all number
    18
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    52 / 251 (20.72%)
    17 / 84 (20.24%)
         occurrences all number
    53
    17
    Infective pulmonary exacerbation of cystic fibrosis
         subjects affected / exposed
    61 / 251 (24.30%)
    17 / 84 (20.24%)
         occurrences all number
    102
    26
    Upper respiratory tract infection
         subjects affected / exposed
    15 / 251 (5.98%)
    6 / 84 (7.14%)
         occurrences all number
    17
    7
    Nasopharyngitis
         subjects affected / exposed
    40 / 251 (15.94%)
    7 / 84 (8.33%)
         occurrences all number
    60
    9

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 May 2021
    Amended to extend the treatment Period by an additional 48 weeks (Part B)to evaluate the safety of ELX/TEZ/IVA beyond 96 weeks of treatment; Revised the statistical analysis section to reflect the updated study design; Clarified language regarding height measurement and ophthalmological examination timings for Parts A and 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
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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