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    Clinical Trial Results:
    An Open-Label Extension Study of Reslizumab 110-mg Fixed, Subcutaneous Dosing in Patients 12 Years of Age and Older with Severe Eosinophilic Asthma

    Summary
    EudraCT number
    2016-004661-23
    Trial protocol
    BE   HU   CZ   DE   FR   ES   PL  
    Global end of trial date
    22 Feb 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    06 Jan 2019
    First version publication date
    06 Jan 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    C38072-AS-30066
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03052725
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Teva Branded Pharmaceutical Products, R&D Inc.
    Sponsor organisation address
    41 Moores Road, Frazer, PA, United States, 19355
    Public contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 888-483-8279, info.era-clinical@teva.de
    Scientific contact
    Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc., 001 888-483-8279, info.era-clinical@teva.de
    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
    31 Jul 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Feb 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to support the long-term safety of reslizumab 110 mg administered sc once every 4 weeks in patients 12 years of age and older with severe eosinophilic asthma that was inadequately controlled on standard-of-care treatment.
    Protection of trial subjects
    This study was conducted in full accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (eg, Code of Federal Regulations [CFR] Title 21, Parts 11, 50, 54, 56, 312, and 314; European Union Directive 2001/20/EC on the approximation of the laws, regulations, and administrative provisions of the Member States relating to the implementation of GCP in the conduct of clinical trials on medicinal products for human use). The principal investigator at each study center was responsible for the conduct and administration of the study at that center and for contacts with study center management, with the IEC/IRB, and with local authorities. Written and/or oral information about the study was provided to all patients in nontechnical language understandable by the patients. The information included an adequate explanation of the aims, methods, anticipated benefits, potential hazards, and insurance arrangements in force. Written informed consent was obtained from each patient before any study procedures or assessments were done. It was explained to the patients that they were free to refuse entry into the study and free to withdraw from the study at any time without prejudice to future treatment. For patients aged 12 to <18 years, a signed and dated informed consent form was obtained from a parent/legally acceptable representative, and a signed and dated assent form was obtained from each patient before any study-specific procedures or assessments were done and after the aims, methods, anticipated benefits, and potential hazards were explained, according to local IRB/IEC requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    10 Mar 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Ukraine: 104
    Country: Number of subjects enrolled
    United States: 84
    Country: Number of subjects enrolled
    Belgium: 19
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    Czech Republic: 17
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Germany: 31
    Country: Number of subjects enrolled
    Hungary: 26
    Country: Number of subjects enrolled
    Israel: 36
    Country: Number of subjects enrolled
    Poland: 19
    Country: Number of subjects enrolled
    Romania: 11
    Country: Number of subjects enrolled
    Russian Federation: 33
    Worldwide total number of subjects
    391
    EEA total number of subjects
    130
    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)
    17
    Adults (18-64 years)
    296
    From 65 to 84 years
    78
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 392 patients with severe eosinophilic asthma rolled over from Study 30025 or 30027, and 391 of these patients (at 125 centers) were enrolled into this extension study and treated with reslizumab. One patient withdrew consent after completing Study 30025 and before enrolling in Study 30066.

    Pre-assignment
    Screening details
    Of the 391 patients enrolled, 112 (29%) enrolled seamlessly and 279 (71%) enrolled non-seamlessly, meaning there was a time gap between completion of the parent study and start of this extension study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Reslizumab 110 mg; Previous Treatment Placebo
    Arm description
    Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
    Arm type
    Experimental

    Investigational medicinal product name
    Reslizumab
    Investigational medicinal product code
    Other name
    CINQAIR®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Reslizumab was administered as 110 mg subcutaneous (sc) injections in the thigh, abdomen, or upper arm(s) once every 4 weeks for a total of 9 doses.

    Arm title
    Reslizumab 110 mg: Previous Treatment Reslizumab
    Arm description
    Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
    Arm type
    Experimental

    Investigational medicinal product name
    Reslizumab
    Investigational medicinal product code
    Other name
    CINQAIR®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Reslizumab was administered as 110 mg subcutaneous (sc) injections in the thigh, abdomen, or upper arm(s) once every 4 weeks for a total of 9 doses.

    Number of subjects in period 1
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Started
    194
    197
    Safety Analysis Set
    194
    196
    Completed
    46
    47
    Not completed
    148
    150
         Pregnancy
    -
    1
         Study terminated by sponsor
    143
    144
         Adverse event, non-fatal
    2
    -
         Consent withdrawn by subject
    3
    4
         Site closure
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Reslizumab 110 mg; Previous Treatment Placebo
    Reporting group description
    Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.

    Reporting group title
    Reslizumab 110 mg: Previous Treatment Reslizumab
    Reporting group description
    Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.

    Reporting group values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab Total
    Number of subjects
    194 197 391
    Age, Customized
    Units: Subjects
        12 to <18 years
    9 8 17
        18 to <65 years
    156 141 297
        >=65 years
    29 48 77
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    50.4 ± 14.85 52.5 ± 15.62 -
    Sex: Female, Male
    Units: Subjects
        Female
    112 122 234
        Male
    82 75 157
    Race/Ethnicity, Customized
    Race
    Units: Subjects
        White
    182 185 367
        Black
    7 10 17
        Asian
    3 2 5
        Other
    2 0 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    18 8 26
        Not Hispanic or Latino
    174 187 361
        Unknown or Not Reported
    2 2 4
    Region Group
    Units: Subjects
        U.S./Canada
    47 41 88
        Europe
    131 136 267
        Other
    16 20 36
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    79.78 ± 17.647 81.22 ± 18.712 -
    Body Mass Index (BMI)
    Units: kg/m^2
        arithmetic mean (standard deviation)
    28.377 ± 5.8288 28.880 ± 5.9672 -
    Systemic Corticosteroid (OCS) Use at Baseline
    Daily OCS dose is defined as total OCS dose in a day (accounting for reported dose and dose frequency) and converting the total daily dose to a prednisone-equivalent dose.
    Units: mg prednisolone or equivalent
        arithmetic mean (standard deviation)
    12.01 ± 10.870 12.26 ± 10.760 -

    End points

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    End points reporting groups
    Reporting group title
    Reslizumab 110 mg; Previous Treatment Placebo
    Reporting group description
    Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.

    Reporting group title
    Reslizumab 110 mg: Previous Treatment Reslizumab
    Reporting group description
    Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.

    Primary: Participants With Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    Participants With Treatment-Emergent Adverse Events (TEAEs) [1]
    End point description
    An adverse event is any untoward medical occurrence, regardless of whether it has a causal relationship with study treatment. In this study, asthma exacerbations should not be recorded as adverse events unless assessed by the investigator as more severe than the patient's usual disease course. The period for reporting treatment-emergent adverse events was defined as the period after the first dose of study drug was administered until the end of treatment visit. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
    End point type
    Primary
    End point timeframe
    Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
    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: No intention to make inference based on stat analysis; the intent is to support clinical judgment.
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: participants
        >=1 TEAE
    102
    114
        >=1 treatment-related TEAE
    7
    6
        >=1 serious TEAE
    5
    11
        >=1 treatment-related, serious TEAE
    0
    0
        >=1 TEAE leading to discontinuation
    2
    0
        >=1 TEAE leading to death
    0
    0
    No statistical analyses for this end point

    Secondary: Participants With Potentially Clinically Significant Abnormal Hematology Values

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    End point title
    Participants With Potentially Clinically Significant Abnormal Hematology Values
    End point description
    Participants are included in the counts if the worst study value reaches the following clinically significant levels: Eosinophils (high): >=1.5*10^9/L and increase >0 Hematocrit (low): >=18 years old: <0.32 L/L for females; <0.37 L/L for males plus a decrease >0 for both or 12 to <18 years old: <0.30 L/L and a decrease >0 for both females and males Hemoglobin (low): >=18 years old: <=95 g/L and decrease >0; 12 to <18 years old: <=100 g/L and decrease >0 Leukocytes (high): >=20*10^9/L and increase >0 Leukocytes (low): <=3*10^9/L and decrease >0 Neutrophils (low): <=1*10^9/L and decrease >0 Platelets (low): <=75*10^9/L and decrease >0
    End point type
    Secondary
    End point timeframe
    Week 0 (baseline), Weeks 8, 24, 36 plus any unscheduled visits
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    192
    192
    Units: participants
        Participants with >=1 abnormality
    8
    5
        Eosinophils (high)
    1
    0
        Hematocrit (low)
    4
    2
        Hemoglobin (low)
    2
    0
        Leukocytes (high)
    0
    1
        Leukocytes (low)
    2
    0
        Neutrophils (low)
    1
    1
        Platelets
    0
    1
    No statistical analyses for this end point

    Secondary: Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values

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    End point title
    Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values
    End point description
    Participants are included in the counts if the worst study value reaches the following clinically significant levels: Alanine Aminotransferase (high): >=3* upper limit of normal (ULN) and increase >0 Aspartate Aminotransferase (high): >=3* upper limit of normal (ULN) and increase >0 Bilirubin (high): >=34.2 micromol/L and increase >0 Blood Urea Nitrogen (high): >=10.71 mmol/L and increase >0 Creatine Phosphokinase (high): >10* ULN and increase >0 Creatine Phosphokinase (medium high): >=3.1*ULN and <=10*ULN and increase >0 Creatinine (high): >=177 micromol/L and increase >0
    End point type
    Secondary
    End point timeframe
    Week 0 (baseline), Weeks 4, 8, 24, 36 plus any unscheduled visits
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    193
    192
    Units: participants
        Participants with >=1 abnormality
    12
    10
        Alanine Aminotransferase (high)
    1
    2
        Aspartate Aminotransferase (high)
    1
    1
        Bilirubin (high)
    2
    1
        Blood Urea Nitrogen (high)
    2
    4
        Creatine Phosphokinase (high)
    2
    1
        Creatine Phosphokinase (medium high)
    6
    4
        Creatinine (high)
    0
    1
    No statistical analyses for this end point

    Secondary: Participants’ Tolerability and Injection Site Reactions by Domain and Worst Overall Severity

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    End point title
    Participants’ Tolerability and Injection Site Reactions by Domain and Worst Overall Severity
    End point description
    The worst finding for participants in each tolerability and injection site domain from all treatment weeks is summarized. Local tolerability at the injection site was assessed approximately 1 hour after study drug administration. Severity was rated on a 4-level scale of none, mild, moderate and severe.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 16, 20, 24, 28, and 36
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: participants
        Pain - None
    191
    194
        Pain - Mild
    3
    2
        Pain - Moderate
    0
    0
        Pain - Severe
    0
    0
        Tenderness - None
    193
    192
        Tenderness - Mild
    1
    4
        Tenderness - Moderate
    0
    0
        Tenderness - Severe
    0
    0
        Erythema - None
    191
    188
        Erythema - Mild
    2
    7
        Erythema - Moderate
    1
    1
        Erythema - Severe
    0
    0
        Warmth - None
    192
    192
        Warmth - Mild
    1
    4
        Warmth - Moderate
    1
    0
        Warmth - Severe
    0
    0
        Swelling - None
    191
    190
        Swelling - Mild
    2
    5
        Swelling - Moderate
    1
    1
        Swelling - Severe
    0
    0
    No statistical analyses for this end point

    Secondary: Participants with Potentially Clinically Significant Abnormal Vital Sign Values

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    End point title
    Participants with Potentially Clinically Significant Abnormal Vital Sign Values
    End point description
    Participants are included in the counts if the worst study value reaches the following clinically significant levels: Diastolic blood pressure (high): >100 mmHg and increase >=12 for participants >=18 years; >85 mmHg and increase >=12 for participants 12 - < 18 years Pulse rate (high): >100 beats/minute and increase >=12 Respiratory rate (high): >24 breaths/minute and increase >=10 for participants >=18 years >20 breaths/minute and increase >=10 for participants 12 - < 18 years Systolic blood pressure (high): >160 mmHg and increase >=30 for participants >=18 years; >130 mmHg and increase >=30 for participants 12 - < 18 years Temperature (high): >38.1 celsius and increase >=1.1 Temperature (low): <35.8 celsius
    End point type
    Secondary
    End point timeframe
    Week 0 (baseline), Weeks 4, 8, 12, 16,20, 24, 28, 32, 36 plus any unscheduled visits
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    193
    196
    Units: participants
        Participants with >=1 abnormality
    20
    16
        Diastolic Blood Pressure - High
    0
    1
        Pulse Rate - High
    1
    2
        Respiratory Rate - High
    2
    0
        Systolic Blood Pressure - High
    2
    0
        Temperature - High
    1
    0
        Temperature - Low
    14
    13
    No statistical analyses for this end point

    Secondary: Annualized Rate of Clinical Asthma Exacerbations (CAEs)

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    End point title
    Annualized Rate of Clinical Asthma Exacerbations (CAEs)
    End point description
    Data is included between the first dose of study drug to the end of treatment visit for completed participants, and the first dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early. Annual rate is defined as the number of events/(duration of treatment [days]/365.25). Participants with zero events are included.
    End point type
    Secondary
    End point timeframe
    Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: CAEs / year
        arithmetic mean (standard deviation)
    0.42 ± 1.104
    0.70 ± 1.538
    No statistical analyses for this end point

    Secondary: Annualized Rate of Clinical Asthma Exacerbations (CAEs) Requiring Asthma-Specific Hospital Admissions or Emergency Room Visits

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    End point title
    Annualized Rate of Clinical Asthma Exacerbations (CAEs) Requiring Asthma-Specific Hospital Admissions or Emergency Room Visits
    End point description
    Data is included between the first dose of study drug to the end of treatment visit for completed participants, and the first dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early. Annual rate is defined as the number of events/(duration of treatment [days]/365.25). Participants with zero events are included.
    End point type
    Secondary
    End point timeframe
    Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: CAEs / year
        arithmetic mean (standard deviation)
    0.06 ± 0.362
    0.11 ± 0.514
    No statistical analyses for this end point

    Secondary: Mean Number of Days of Hospital Stay During the Treatment Period

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    End point title
    Mean Number of Days of Hospital Stay During the Treatment Period
    End point description
    Participants with no hospitalizations are included.
    End point type
    Secondary
    End point timeframe
    Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: days
        arithmetic mean (standard deviation)
    0.25 ± 1.658
    1.02 ± 7.848
    No statistical analyses for this end point

    Secondary: Mean Number of School/Work Days Missed Due to Asthma During the Treatment Period

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    End point title
    Mean Number of School/Work Days Missed Due to Asthma During the Treatment Period
    End point description
    Participants with no school or work days missed due to asthma are included in the counts.
    End point type
    Secondary
    End point timeframe
    Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: days
        arithmetic mean (standard deviation)
    0.11 ± 1.202
    0.00 ± 0.000
    No statistical analyses for this end point

    Secondary: Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change from Baseline Values at Weeks 8, 24 and 36

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    End point title
    Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change from Baseline Values at Weeks 8, 24 and 36
    End point description
    The FEV1 is the volume of air that can be forcibly exhaled from the lungs in the first second, measured in liters. Pre-bronchodilator spirometry assessments at designated clinic visits (weeks 0, 8, and 24, and 36) should only be performed after withholding short-acting bronchodilators (ie, inhaled short-acting beta-adrenergic agonists and/or short-acting anticholinergics) for at least 6 hours and long-acting bronchodilators ie, inhaled long-acting beta-adrenergic agonists and long acting anticholinergic agents) for at least 12 or 24 hours, according to their labeled dose schedule.
    End point type
    Secondary
    End point timeframe
    Week 0 (baseline), Weeks 8, 24, 36
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: liters
    arithmetic mean (standard deviation)
        Baseline - observed value (n=179, 177)
    2.162 ± 0.980
    2.117 ± 0.927
        Change at Week 8 (n=175, 168)
    0.099 ± 0.704
    0.031 ± 0.529
        Change at Week 24 (n=99, 91)
    0.169 ± 0.851
    -0.020 ± 0.472
        Change at Week 36 (n=32, 31)
    0.245 ± 0.677
    0.010 ± 0.550
    No statistical analyses for this end point

    Secondary: Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change from Baseline Values at Weeks 1, 4, 8, 24 and 36

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    End point title
    Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change from Baseline Values at Weeks 1, 4, 8, 24 and 36
    End point description
    A weekly average of daily morning ambulatory FEV1 (measured by the handheld spirometry device) was derived using 7-day window intervals. The average was calculated as the sum of all values divided by the number of non-missing assessments. There will be no imputation of missing data. At least 4 of the 7 measurements need to be recorded for a week to be included in the analysis; otherwise the week was treated as missing.
    End point type
    Secondary
    End point timeframe
    Week 0 (baseline), Weeks 1, 4, 8, 24, 36
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: liters
    arithmetic mean (standard deviation)
        Baseline - observed value (n=192, 193)
    2.057 ± 0.814
    2.027 ± 0.848
        Change at Week 1 (n=190, 186)
    0.002 ± 0.345
    -0.044 ± 0.291
        Change at Week 4 (n=184, 190)
    0.051 ± 0.490
    -0.049 ± 0.000
        Change at Week 8 (n=185, 187)
    0.028 ± 0.463
    -0.039 ± 0.345
        Change at Week 24 (n=150, 146)
    0.051 ± 0.492
    -0.062 ± 0.403
        Change at Week 36 (n=33, 34)
    0.061 ± 0.273
    -0.053 ± 0.465
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36

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    End point title
    Percent Change from Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36
    End point description
    Daily OCS dose is defined as total OCS dose in a day (accounting for reported dose and dose frequency) and converting the total daily dose to a prednisone-equivalent dose. Baseline dose is the prescribed OCS dose on the day of first dose of study drug in this study. Dose at Weeks 16-20 and 32-36 is the mean of all daily OCS doses during the week range. Percent change = 100 * (absolute change / baseline dose)
    End point type
    Secondary
    End point timeframe
    Week 0 (baseline), Weeks 16-20, Weeks 32-36
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: percent change
    arithmetic mean (standard deviation)
        % change at Week 16-20 (n=46, 45)
    -2.19 ± 51.347
    -6.96 ± 40.904
        % change at Week 32-36 (n=11, 11)
    -8.44 ± 24.236
    -8.75 ± 29.666
    No statistical analyses for this end point

    Secondary: Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change from Baseline Values at Weeks 1, 4, 8, 24 and 36

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    End point title
    Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change from Baseline Values at Weeks 1, 4, 8, 24 and 36
    End point description
    Total inhalations of reliever bronchodilator medication (eg, short-acting beta-agonist [SABA]) measured using weekly averages. The average was calculated as the sum of all values divided by the number of non-missing assessments. There was no imputation of missing data. At least 4 of the 7 measurements need to be recorded for a week to be included in the analysis; otherwise the week was treated as missing.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 1, 4, 8, 24, 36
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: inhalations
    arithmetic mean (standard deviation)
        Baseline - observed values (n=171, 170)
    2.4 ± 3.39
    2.6 ± 3.10
        Change at Week 1 (n=158, 160)
    -0.4 ± 1.30
    -0.4 ± 1.17
        Change at Week 4 (n=153, 162)
    -0.6 ± 1.86
    -0.5 ± 1.50
        Change at Week 8 (n=155, 163)
    -0.7 ± 1.79
    -0.6 ± 1.61
        Change at Week 24 (n=121, 118)
    -0.8 ± 1.92
    -0.8 ± 1.78
        Change at Week 36 (n=23, 25)
    -0.5 ± 1.69
    -0.6 ± 1.80
    No statistical analyses for this end point

    Secondary: Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change from Baseline Values at Weeks 8, 24 and 36

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    End point title
    Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change from Baseline Values at Weeks 8, 24 and 36
    End point description
    The ACQ-6 is a validated asthma assessment tool that has been widely used. There are 6 self-assessment questions. Each item on the ACQ-6 has a possible score ranging from 0 to 6 and the total score is the mean of all responses. The seven-point response scale: 0 = ‘totally controlled’ and 6 = ‘severely uncontrolled.’ Negative change from baseline values indicate improved asthma control.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 8, 24, 36
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline - observed values (n=193, 195)
    1.72 ± 1.098
    1.69 ± 1.171
        Change at Week 8 (n=191, 192)
    -0.31 ± 0.777
    -0.20 ± 0.718
        Change at Week 24 (n=150, 145)
    -0.30 ± 0.936
    -0.23 ± 0.771
        Change at Week 36 (n=78, 77)
    -0.34 ± 0.855
    -0.28 ± 0.867
    No statistical analyses for this end point

    Secondary: Asthma Quality of Life Questionnaire Administered to Participants Ages 12-70 years (AQLQ +12) Overall Score: Baseline Values and Change from Baseline Values at Weeks 8, 24 and 36

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    End point title
    Asthma Quality of Life Questionnaire Administered to Participants Ages 12-70 years (AQLQ +12) Overall Score: Baseline Values and Change from Baseline Values at Weeks 8, 24 and 36
    End point description
    The AQLQ +12 is a modified version of the standardized AQLQ, which was developed to measure functional impairments experienced by adults ≥17 years of age. The AQLQ +12 is valid for patients 12 to 70 years of age and includes 32 questions in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and score each of the questions on a 7-point scale, where 7=not at all limited and 1=totally limited. The overall score of the AQLQ +12 was derived as the average of the 32 questions, thus, the total score ranges from 1 (indicates "total impairment") to 7 (indicates "no impairment"). Positive change from baseline values indicate improved quality of life.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 8, 24, 36
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    187
    179
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline - observed value (n=186, 176)
    5.04 ± 1.249
    5.14 ± 1.270
        Change at Week 8 (n=185, 173)
    0.30 ± 0.716
    0.14 ± 0.700
        Change at Week 24 (n=143, 131)
    0.28 ± 0.727
    0.20 ± 0.830
        Change at Week 36 (n=72, 68)
    0.32 ± 0.835
    0.19 ± 0.948
    No statistical analyses for this end point

    Secondary: Participants with Treatment-Emergent Anti-Drug Antibody (ADA) Responses

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    End point title
    Participants with Treatment-Emergent Anti-Drug Antibody (ADA) Responses
    End point description
    Treatment-emergent responses were defined as a positive sample post-baseline (negative baseline) OR a titer increase of >=4-fold relative to a positive baseline sample. Two types of antibody assay were performed, an immunogenicity status assay (ADA) and neutralizing assay (NAb). The ADA assay produces a positive or negative result. For samples with a positive result, a neutralizing assay was performed, which also produces a positive or negative result.
    End point type
    Secondary
    End point timeframe
    Baseline - date of randomization in the previous study (C38072-AS-30025 or C38072-AS-30027), Weeks 8, 24, 36 or early withdrawal
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    194
    196
    Units: participants
    11
    9
    No statistical analyses for this end point

    Secondary: Participants with Treatment-Emergent Anti-Drug Antibody (ADA) At the End-0f-Study Visit (Week 51)

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    End point title
    Participants with Treatment-Emergent Anti-Drug Antibody (ADA) At the End-0f-Study Visit (Week 51)
    End point description
    The endpoint was defined to evaluate immunogenicity after study drug washout since the end of study visit on Week 51 was to be 19 weeks after the final dose of study drug. Due to the early termination of the study no participants had an end of study visit.
    End point type
    Secondary
    End point timeframe
    Week 51
    End point values
    Reslizumab 110 mg; Previous Treatment Placebo Reslizumab 110 mg: Previous Treatment Reslizumab
    Number of subjects analysed
    0 [2]
    0 [3]
    Units: participants
    Notes
    [2] - Due to early termination, no participants had an end of study visit.
    [3] - Due to early termination, no participants had an end of study visit.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Reslizumab 110 mg
    Reporting group description
    Participants were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.

    Serious adverse events
    Reslizumab 110 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 390 (4.10%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Post procedural haematoma
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    2 / 390 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Synovial cyst
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    1 / 390 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 390 (0.77%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Reslizumab 110 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    70 / 390 (17.95%)
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    23 / 390 (5.90%)
         occurrences all number
    24
    Viral upper respiratory tract infection
         subjects affected / exposed
    49 / 390 (12.56%)
         occurrences all number
    62

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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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