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    Clinical Trial Results:
    A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study in Cat-Allergic Patients with Asthma to Evaluate the Efficacy of a Single Dose of REGN1908-1909 to Reduce Bronchoconstriction Upon Cat Allergen Challenge

    Summary
    EudraCT number
    2018-002477-22
    Trial protocol
    FR  
    Global end of trial date
    06 Apr 2020

    Results information
    Results version number
    v2(current)
    This version publication date
    16 Sep 2021
    First version publication date
    17 Apr 2021
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    R1908-1909-ALG-1703
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03838731
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Regeneron Pharnaceuticals, Inc.
    Sponsor organisation address
    777 Old Saw Mill River Rd., Tarrytown, NY, United States, 10591
    Public contact
    Clinical Trials Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
    Scientific contact
    Clinical Trials Administrator, Regeneron Pharnaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Apr 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Apr 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the prophylactic efficacy of REGN1908-1909 (anti-Fel d 1) administered as a single dose on day 1 in cat-allergic asthmatic subjects not living with a cat in the prevention of a Controlled Cat Allergen Challenge-induced early asthmatic response (EAR) assessed by measures of lung function (forced expiratory volume in 1 second [FEV1]) compared to placebo-treated subjects on day 8.
    Protection of trial subjects
    This clinical study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with the International Council for Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    12 Feb 2019
    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
    France: 56
    Worldwide total number of subjects
    56
    EEA total number of subjects
    56
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    56
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 130 subjects were screened for study eligibility. Screen failures were mostly attributed to eligibility criteria not being met. The study was conducted at one site in France.

    Pre-assignment
    Screening details
    A total of 56 subjects were randomized in a 1:1 ratio to receive a single dose of either 600 milligrams (mg) of REGN1908-1909 or matching placebo.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Subjects received a single dose of matching placebo
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Single subcutaneous (SC) dose of matching placebo

    Arm title
    REGN1908-1909 600 mg
    Arm description
    Subjects received a single 600 mg dose of REGN1908-1909
    Arm type
    Experimental

    Investigational medicinal product name
    REGN1908-1909
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Single subcutaneous (SC) dose of REGN1908 and REGN1909

    Number of subjects in period 1
    Placebo REGN1908-1909 600 mg
    Started
    27
    29
    Completed
    26
    28
    Not completed
    1
    1
         Withdrawal of consent
    1
    -
         Pregnancy
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received a single dose of matching placebo

    Reporting group title
    REGN1908-1909 600 mg
    Reporting group description
    Subjects received a single 600 mg dose of REGN1908-1909

    Reporting group values
    Placebo REGN1908-1909 600 mg Total
    Number of subjects
    27 29 56
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    27 29 56
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    30.2 ± 8.8 28.4 ± 7.1 -
    Sex: Female, Male
    Units: Subjects
        Female
    17 18 35
        Male
    10 11 21
    Race, Customized
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    0 1 1
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    3 0 3
        White
    24 27 51
        Other
    0 1 1
        Unknown or Not Reported
    0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    1 1 2
        Not Hispanic or Latino
    26 28 54
        Unknown or Not Reported
    0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received a single dose of matching placebo

    Reporting group title
    REGN1908-1909 600 mg
    Reporting group description
    Subjects received a single 600 mg dose of REGN1908-1909

    Primary: Time to Early Asthmatic Response (EAR) upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8

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    End point title
    Time to Early Asthmatic Response (EAR) upon Controlled Cat Allergen Challenge in an Environmental Exposure Unit (EEU) on Day 8
    End point description
    Time to EAR was defined as the time to a ≥20% reduction in FEV1 or when the subject voluntarily departed the EEU due to clinically significant allergic and/or asthmatic symptoms.
    End point type
    Primary
    End point timeframe
    Day 8
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Minutes
        median (confidence interval 95%)
    51 (33.92 to 70.70)
    99999 (130.87 to 99999)
    Statistical analysis title
    Placebo vs. REGN1908-1909 600 mg
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0083
    Method
    Cox Hazard Proportional
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.17
         upper limit
    0.77

    Secondary: Time to EAR upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85

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    End point title
    Time to EAR upon Controlled Cat Allergen Challenge in an EEU on Days 29, 57, and 85
    End point description
    Time to EAR was defined as the time to a ≥20% reduction in FEV1 or when the subject voluntarily departed the EEU due to clinically significant allergic and/or asthmatic symptoms
    End point type
    Secondary
    End point timeframe
    Days 29, 57 and 85
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Minutes
    median (confidence interval 95%)
        Day 29
    41 (31.38 to 61.13)
    99999 (131.22 to 99999)
        Day 57
    56 (40.52 to 80.63)
    232 (81.05 to 99999)
        Day 85
    41 (31.03 to 60.93)
    99999 (90.97 to 99999)
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    < 0.0001
    Method
    Cox Hazard Model
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.12
         upper limit
    0.48
    Notes
    [1] - Day 29
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 85
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0003
    Method
    Cox Hazard Model
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.13
         upper limit
    0.56
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 57
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0222
    Method
    Cox Hazard Model
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.22
         upper limit
    0.89

    Secondary: Percent Change in Normalized Area Under the Curve (AUC) of the Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge over Exposure Interval from Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85

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    End point title
    Percent Change in Normalized Area Under the Curve (AUC) of the Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge over Exposure Interval from Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85
    End point description
    The AUC was analyzed by mixed-effect model repeated measures (MMRM) with the treatment, time, treatment-by-time interaction, and day of challenge as factors and baseline FEV1 as a continuous covariate. Full analysis set; Here 'n' = number of evaluable participants analyzed at each time point. For each participant at each controlled cat allergen challenge, AUC was calculated over the time period of 0 to 2 hours, with last observation carried forward used to impute values out to 2 hours if the patients remained in EEU for less than 2 hours. The AUCs were calculated using the trapezoidal rule and were normalized by dividing by the length of time (2 hours).
    End point type
    Secondary
    End point timeframe
    Days 8, 29, 57, and 85
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Percentage of change
    least squares mean (standard error)
        Day 8
    1.59 ± 2.58
    15.15 ± 2.50
        Day 29
    0.46 ± 3.60
    16.67 ± 3.43
        Day 57
    1.77 ± 3.55
    14.07 ± 3.43
        Day 85
    0.20 ± 3.28
    12.73 ± 3.14
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    13.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.35
         upper limit
    20.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.59
    Notes
    [2] - Day 8
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.002
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    16.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.18
         upper limit
    26.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.97
    Notes
    [3] - Day 29
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority [4]
    P-value
    = 0.016
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    12.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.4
         upper limit
    22.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.94
    Notes
    [4] - Day 57
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority [5]
    P-value
    = 0.008
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    12.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.43
         upper limit
    21.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.54
    Notes
    [5] - Day 85

    Secondary: Change in Normalized Area Under the Curve (AUC) of the Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge over Exposure Interval from Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85

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    End point title
    Change in Normalized Area Under the Curve (AUC) of the Forced Expiratory Volume in 1 Second (FEV1) Induced by a Controlled Cat Allergen Challenge over Exposure Interval from Baseline to Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85
    End point description
    The AUC was analyzed by mixed-effect model repeated measures (MMRM) with the treatment, time, treatment-by-time interaction, and day of challenge as factors and baseline FEV1 as a continuous covariate. Full analysis set; Here "n" = number of evaluable participants analyzed at each time point. For each participant at each controlled cat allergen challenge, AUC was calculated over the time period of 0 to 2 hours, with last observation carried forward used to impute values out to 2 hours if the patients remained in EEU for less than 2 hours. The AUCs were calculated using the trapezoidal rule and were normalized by dividing by the length of time (2 hours).
    End point type
    Secondary
    End point timeframe
    Days 8, 29, 57 and 85
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Liters (L)
    least squares mean (standard error)
        Day 8
    0.01 ± 0.06
    0.38 ± 0.06
        Day 29
    -0.03 ± 0.08
    0.43 ± 0.08
        Day 57
    0.00 ± 0.08
    0.34 ± 0.07
        Day 85
    -0.05 ± 0.08
    0.32 ± 0.08
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 8
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.21
         upper limit
    0.53
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 29
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.23
         upper limit
    0.68
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 57
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.13
         upper limit
    0.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 85
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.15
         upper limit
    0.47
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.11

    Secondary: Change from Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85

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    End point title
    Change from Baseline in the Normalized AUC of Patient-Assessed Nasal Symptoms Induced by a Controlled Cat Allergen Challenge over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85
    End point description
    Individual nasal symptoms, including rhinorrhea, nasal congestion, nasal itching, and sneezing were evaluated on a 4-point Likert scale (0, none; 1, mild; 2, moderate; and 3, severe) and combined to give the Total Nasal Symptom Score (TNSS) with a maximum score of 12. Scale range is 0-12. The higher the total, the more severe the symptoms. Full analysis set; Here 'n' = number of evaluable participants analyzed at each time point. For each participant at each controlled cat allergen challenge, AUC was calculated over the time period of 0 to 2 hours, with last observation carried forward used to impute values out to 2 hours if participants remained in EEU for less than 2 hours. AUCs were calculated using trapezoidal rule and were normalized by dividing by the length of time (2 hours).
    End point type
    Secondary
    End point timeframe
    Days 8, 29, 57 and 85
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Scores on a scale
    least squares mean (standard error)
        Day 8
    -0.71 ± 0.38
    -0.49 ± 0.38
        Day 29
    -0.70 ± 0.37
    -1.39 ± 0.34
        Day 57
    -0.93 ± 0.43
    -0.83 ± 0.43
        Day 85
    -0.49 ± 0.43
    -1.37 ± 0.41
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 8
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.675
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0.22
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.85
         upper limit
    1.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.53
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 29
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.182
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    -0.68
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.7
         upper limit
    0.33
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.51
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 57
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.866
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.12
         upper limit
    1.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 85
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.146
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    -0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.08
         upper limit
    0.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6

    Secondary: Change from Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85

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    End point title
    Change from Baseline in the Normalized AUC in Patient-Assessed Ocular Symptoms Induced by a Controlled Cat Allergen Challenge over the Exposure Interval to the Controlled Cat Allergen Challenge on Days 8, 29, 57, and 85
    End point description
    Individual ocular symptoms for itching/burning, redness, swelling/puffiness, and tearing/watery eyes were evaluated on a 4-point Likert scale (0, none; 1, mild; 2, moderate; and 3, severe) and combined to give the TOSS, with a maximum score of 12. Scale range is 0-12. The higher the score, the more severe the symptoms. Full analysis set; Here 'n' = number of evaluable participants analyzed at each time point. For each participant at each controlled cat allergen challenge, AUC was calculated over the time period of 0 to 2 hours, with last observation carried forward used to impute values out to 2 hours if participants remained in EEU for less than 2 hours. AUCs were calculated using trapezoidal rule and were normalized by dividing by the length of time (2 hours).
    End point type
    Secondary
    End point timeframe
    Days 8, 29, 57 and 85
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Scores on a scale
    least squares mean (standard error)
        Day 8
    -0.37 ± 0.17
    -0.23 ± 0.17
        Day 29
    -0.43 ± 0.15
    -0.43 ± 0.14
        Day 57
    -0.40 ± 0.15
    -0.34 ± 0.15
        Day 85
    -0.36 ± 0.11
    -0.51 ± 0.10
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 8
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.572
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.35
         upper limit
    0.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.24
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 29
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.997
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.41
         upper limit
    0.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 57
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.756
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.36
         upper limit
    0.49
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 85
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.333
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    -0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.46
         upper limit
    0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15

    Secondary: Mean Change from Baseline in Cat Allergen Quantity as Experienced by Subjects During Exposure on Days 8, 29, 57, and 85

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    End point title
    Mean Change from Baseline in Cat Allergen Quantity as Experienced by Subjects During Exposure on Days 8, 29, 57, and 85
    End point description
    Cat Allergen Exposure Tolerated in ng = Minute Ventilation (L/min) x Allergen Concentration (ng/m3) x Time in EEU (minutes), where 1 L/min = 0.001 m3/min. The change in cat allergen quantity (tolerated exposure) from the baseline Cat Allergen Challenge, will be analyzed using a similar MMRM model with treatment, visit and treatment by-visit interaction as factors and the cat allergen quantity tolerated in the baseline Controlled Cat Allergen Challenge as a covariate. Full analysis set: included all randomized participants who received any investigational product and had completed the Day 8 Cat Allergen Challenge; Here 'n' = number of evaluable participants analyzed at each time point
    End point type
    Secondary
    End point timeframe
    Days 8, 29, 57 and 85
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Nanograms (ng)
    least squares mean (standard error)
        Day 8
    19.55 ± 8.93
    59.05 ± 8.70
        Day 29
    14.14 ± 8.67
    68.21 ± 8.21
        Day 57
    21.94 ± 10.23
    55.38 ± 9.93
        Day 85
    12.93 ± 9.29
    54.03 ± 8.94
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 8
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    39.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    14.36
         upper limit
    64.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    12.5
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 29
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    39.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    14.36
         upper limit
    64.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    12.5
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 57
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.023
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    33.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.79
         upper limit
    62.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    14.28
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 85
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    41.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.1
         upper limit
    67.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    12.92

    Secondary: Percent Change in Cat Allergen Quantity as Experienced by Subjects During Exposure on Days 8, 29, 57, and 85

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    End point title
    Percent Change in Cat Allergen Quantity as Experienced by Subjects During Exposure on Days 8, 29, 57, and 85
    End point description
    Cat Allergen Exposure Tolerated in ng = Minute Ventilation (L/min) x Allergen Concentration (ng/m3) x Time in EEU (minutes), where 1 L/min = 0.001 m3/min. The change in cat allergen quantity (tolerated exposure) from the baseline Cat Allergen Challenge, will be analyzed using a similar MMRM model with treatment, visit and treatment by-visit interaction as factors and the cat allergen quantity tolerated in the baseline Controlled Cat Allergen Challenge as a covariate. Full analysis set: included all randomized participants who received any investigational product and had completed the Day 8 Cat Allergen Challenge; Here 'n' = number of evaluable participants analyzed at each time point
    End point type
    Secondary
    End point timeframe
    Days 8, 29, 57 and 85
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Percentage of change
    least squares mean (standard error)
        Day 8
    119.86 ± 73.22
    325.29 ± 70.79
        Day 29
    93.62 ± 71.48
    338.22 ± 68.26
        Day 57
    118.08 ± 69.58
    301.11 ± 67.11
        Day 85
    76.75 ± 82.08
    317.76 ± 78.84
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 8
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.049
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    205.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    410.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    102.09
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 29
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.017
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    244.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    45.6
         upper limit
    443.59
    Variability estimate
    Standard error of the mean
    Dispersion value
    99.05
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 57
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.064
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    183.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.29
         upper limit
    377.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    96.91
    Statistical analysis title
    Placebo, REGN1908-1909 600 mg
    Statistical analysis description
    Day 85
    Comparison groups
    Placebo v REGN1908-1909 600 mg
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.039
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    241.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    12.44
         upper limit
    469.57
    Variability estimate
    Standard error of the mean
    Dispersion value
    114

    Secondary: Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) through End of Study

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    End point title
    Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) through End of Study
    End point description
    Adverse events and serious adverse events were collected from the time of informed consent signature and then at each visit until the end of the study with the exception of symptoms that occurred in response to the EEU within 24 hours following the EEU. Safety Analysis Set (SAF): included all subjects who received any investigational product and were analyzed as treated.
    End point type
    Secondary
    End point timeframe
    Baseline to 16 weeks
    End point values
    Placebo REGN1908-1909 600 mg
    Number of subjects analysed
    27
    29
    Units: Events
    number (not applicable)
        Non-serious TEAEs
    66
    76
        Serious TEAEs
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline (day 1) to the end of study (week 16)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    REGN1908-1909 600mg
    Reporting group description
    Subjects received single 600 mg dose of REGN1908-1909

    Reporting group title
    Placebo
    Reporting group description
    Subjects received a single dose of matching placebo

    Serious adverse events
    REGN1908-1909 600mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 27 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    REGN1908-1909 600mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    22 / 29 (75.86%)
    19 / 27 (70.37%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 27 (0.00%)
         occurrences all number
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    11 / 29 (37.93%)
    16 / 27 (59.26%)
         occurrences all number
    19
    35
    Asthma exercise induced
         subjects affected / exposed
    1 / 29 (3.45%)
    3 / 27 (11.11%)
         occurrences all number
    1
    3
    Rhinitis allergic
         subjects affected / exposed
    5 / 29 (17.24%)
    2 / 27 (7.41%)
         occurrences all number
    5
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 29 (17.24%)
    2 / 27 (7.41%)
         occurrences all number
    5
    2
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    3 / 29 (10.34%)
    0 / 27 (0.00%)
         occurrences all number
    3
    0
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    3 / 29 (10.34%)
    4 / 27 (14.81%)
         occurrences all number
    3
    4
    Injection site pain
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 27 (3.70%)
         occurrences all number
    2
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 27 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Nasopharyngitis
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 27 (7.41%)
         occurrences all number
    2
    2

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Dec 2018
    Added exploratory objective information; clarification of several sections and study exit parameters, addition of Independent Data Monitoring Committee (IDMC) section; updates to inclusion and exclusion criteria; editorial changes
    20 May 2019
    Clarified language in adverse events; clarified inclusion and exclusion criteria information; clarified timing of analysis; procedural clarifications of timing of events, tests and measurements; added clarification on concomitant medications; other administrative updates

    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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