Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    PEANUT ALLERGY ORAL IMMUNOTHERAPY STUDY OF AR101 FOR DESENSITIZATION IN CHILDREN AND ADULTS (PALISADE) FOLLOW-ON STUDY

    Summary
    EudraCT number
    		 2016-004941-94
    Trial protocol
    		 IE   GB   SE   DE   ES   NL   IT  
    Global end of trial date
    31 May 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Jul 2021
    First version publication date
    02 Jul 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ARC004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02993107
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Aimmune Therapeutics Inc.
    Sponsor organisation address
    8000 Marina Blvd, Suite 300, Brisbane, United States, 94005
    Public contact
    Director of Regulatory Affairs, Aimmune Therapeutics Inc., +1 (650)409-5164, RegulatoryAffairs@aimmune.com
    Scientific contact
    Director of Regulatory Affairs, Aimmune Therapeutics Inc., +1 (650)409-5164, RegulatoryAffairs@aimmune.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001734-PIP01-14
    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
    14 Feb 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 May 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    31 May 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to determine the safety, tolerability and efficacy of AR101 characterized oral desensitization immunotherapy using alternative maintenance dosing intervals.
    Protection of trial subjects
    • Education of patients to notify sites of allergic symptoms occurring at home. • Patient emergency card, dos and don’t card, home dosing card. • Patients/caregivers asked to carry epi-pen with them at all times during study. • Patient advised to go to local emergency unit outside of normal clinical working hours. • Patient advised to report rare or unforeseen AEs immediately. • Advised to practice usual peanut avoidance • Specific reporting/monitoring of AEIs, Gastrointestinal AEs (monitoring and follow-up for EOE), capture of AEs in patient diaries, EDC, SAE reporting, study and individual stopping rules & in clinic, supervised up-dosing, including observation timelines prior to Clinic departure.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Dec 2016
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy, Regulatory reason, Scientific research
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Spain: 15
    Country: Number of subjects enrolled
    Sweden: 7
    Country: Number of subjects enrolled
    United Kingdom: 16
    Country: Number of subjects enrolled
    Germany: 15
    Country: Number of subjects enrolled
    Ireland: 15
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Canada: 23
    Country: Number of subjects enrolled
    United States: 290
    Worldwide total number of subjects
    388
    EEA total number of subjects
    75
    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)
    230
    Adolescents (12-17 years)
    128
    Adults (18-64 years)
    30
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 442 subjects who completed the ARC003 (PALISADE) study were eligible for participation in this study and were screened for inclusion of which 388 were enrolled in this study.

    Pre-assignment
    Screening details
    		 Subjects who met all of the following criteria were eligible for enrolment: • Completion of ARC003 • Written informed consent and/or assent from subject/guardian as appropriate • Continued use of effective birth control by female subjects of childbearing potential

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Group 1
    Arm description
    		 Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during initial dose escalation (day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 to 300 mg/day for 22 to 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 to 28 weeks). A DBPCFC using peanut protein (not AR101) of doses up to 2000 mg (4043 mg cumulative) was conducted after approximately 6 months of maintenance treatment. This was followed by an extended maintenance period in subjects tolerating at least 300mg in the DBPCFC where the subjects may be dosed at gradually dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AR101
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder
    Routes of administration
    Oral use
    Dosage and administration details
    AR101 drug product was supplied in 2 presentations. These were capsules containing 0.5, 1, 10, 20 and 100mg of peanut protein and sealed sachets containing 300mg of peanut protein. Subjects in initial escalation and up-dosing phases received the capsule presentation. Subjects in maintenance phase received the sachet presentation according to their allocated dosing schedules. If dose-reduction was required, subjects were dispensed the appropriate capsule packs.

    Arm title
    		 Group 2, Cohort 1
    Arm description
    		 Group 2, Cohort 1 subjects were the first 120 (approximately) of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day (once daily, QD) for 28 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AR101
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder
    Routes of administration
    Oral use
    Dosage and administration details
    AR101 drug product was supplied in 2 presentations. These were capsules containing 0.5, 1, 10, 20 and 100mg of peanut protein and sealed sachets containing 300mg of peanut protein. Subjects in initial escalation and up-dosing phases received the capsule presentation. Subjects in maintenance phase received the sachet presentation according to their allocated dosing schedules. If dose-reduction was required, subjects were dispensed the appropriate capsule packs.

    Arm title
    		 Group 2, Cohort 2
    Arm description
    		 Group 2, Cohort 2 subjects comprised 50(approximately) of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every other day (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks for a total of 28 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AR101
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder
    Routes of administration
    Oral use
    Dosage and administration details
    AR101 drug product was supplied in 2 presentations. These were capsules containing 0.5, 1, 10, 20 and 100mg of peanut protein and sealed sachets containing 300mg of peanut protein. Subjects in initial escalation and up-dosing phases received the capsule presentation. Subjects in maintenance phase received the sachet presentation according to their allocated dosing schedules. If dose-reduction was required, subjects were dispensed the appropriate capsule packs.

    Arm title
    		 Group 2, Cohort 3A
    Arm description
    		 Group 2, Cohort 3A subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 56 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AR101
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder
    Routes of administration
    Oral use
    Dosage and administration details
    AR101 drug product was supplied in 2 presentations. These were capsules containing 0.5, 1, 10, 20 and 100mg of peanut protein and sealed sachets containing 300mg of peanut protein. Subjects in initial escalation and up-dosing phases received the capsule presentation. Subjects in maintenance phase received the sachet presentation according to their allocated dosing schedules. If dose-reduction was required, subjects were dispensed the appropriate capsule packs.

    Arm title
    		 Group 2, Cohort 3B
    Arm description
    		 Group 2, Cohort 3B subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 28 weeks, 300 mg/day every other (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks (total of 56 weeks).
    Arm type
    		 Experimental

    Investigational medicinal product name
    AR101
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder
    Routes of administration
    Oral use
    Dosage and administration details
    AR101 drug product was supplied in 2 presentations. These were capsules containing 0.5, 1, 10, 20 and 100mg of peanut protein and sealed sachets containing 300mg of peanut protein. Subjects in this treatment arm received the sealed sachets containing 300mg of peanut protein every day (QD) for 28 weeks, 300 mg/day every other (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks (total of 56 weeks). If dose-reduction was required, subjects were dispensed the appropriate capsule packs.

    Arm title
    		 Group 2, Cohort 3C
    Arm description
    		 Group 2, Cohort 3C subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 28 weeks, 300 mg/day every other (QOD) for 4 weeks, twice weekly (BIW) for 24 weeks then once weekly (QW) for 28 weeks (total of 84 weeks).
    Arm type
    		 Experimental

    Investigational medicinal product name
    AR101
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral powder
    Routes of administration
    Oral use
    Dosage and administration details
    AR101 drug product was supplied in 2 presentations. These were capsules containing 0.5, 1, 10, 20 and 100mg of peanut protein and sealed sachets containing 300mg of peanut protein. Subjects in this treatment arm received the sealed sachets containing 300mg of peanut protein every day (QD) for 4 weeks, 300 mg/day every other (QOD) for 4 weeks, twice weekly (BIW) for 24 weeks then once weekly (QW) for 28 weeks (total of 84 weeks). If dose-reduction was required, subjects were dispensed the appropriate capsule packs.

    Number of subjects in period 1
    		Group 1 Group 2, Cohort 1 Group 2, Cohort 2 Group 2, Cohort 3A Group 2, Cohort 3B Group 2, Cohort 3C
    Started
    113
    120
    50
    35
    34
    36
    Completed
    62
    107
    39
    29
    22
    21
    Not completed
    51
    13
    11
    6
    12
    15
         Physician decision
    1
    -
    1
    -
    -
    -
         Consent withdrawn by subject
    32
    7
    7
    3
    6
    2
         Adverse event, non-fatal
    12
    4
    1
    1
    3
    5
         Other
    2
    1
    1
    1
    2
    3
         Sponsor Decision
    4
    -
    1
    1
    -
    4
         Lost to follow-up
    -
    1
    -
    -
    -
    1
         Protocol deviation
    -
    -
    -
    -
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Post-Allocation
    Reporting group description
    		 Subjects aged 4 to 55 years who completed study ARC003 (PALISADE).

    Reporting group values
    		 Post-Allocation Total
    Number of subjects
    		 388 388
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 230 230
        Adolescents (12-17 years)
    		 128 128
        Adults (18-64 years)
    		 30 30
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age continuous
    Subject age at screening (years)
    Units: years
        median (full range (min-max))
    		 10 (4 to 17) -
    Gender categorical
    Units: Subjects
        Female
    		 165 165
        Male
    		 223 223
    Subject analysis sets

    Subject analysis set title
    Safety Population Ages 4-17: Group 1 (All Study Periods)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during initial dose escalation (IDE; day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 to 300 mg/day for 22 to 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 to 28 weeks). A DBPCFC, using peanut protein (not AR101) of doses up to 2000 mg (4043 mg cumulative), was conducted after approximately 6 months of maintenance treatment. This was followed by an extended maintenance period in subjects tolerating at least 300mg in the DBPCFC where the subjects may be doses at gradually dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks. This analysis set evaluates all the above study phases. This analysis set includes events from subjects in all study (IDE, Updosing and maintenance) periods.

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 1
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 1 subjects were the first 120 of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day (once daily, QD) for 28 weeks.

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 2
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 2 subjects comprised 50 of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every other day (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks for a total of 28 weeks.

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 3A
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 3A subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 56 weeks.

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 3B
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 3B subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 28 weeks, 300 mg/day every other (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks (total of 56 weeks).

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 3C
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 3C subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 4 weeks, 300 mg/day every other (QOD) for 4 weeks, twice weekly (BIW) for 24 weeks then once weekly (QW) for 28 weeks (total of 84 weeks).

    Subject analysis set title
    Safety Population Ages 4-17: Group 1 (IDE and Updosing)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during initial dose escalation (IDE; day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 to 300 mg/day for 22 to 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 to 28 weeks). A DBPCFC, using peanut protein (not AR101) of doses up to 2000 mg (4043 mg cumulative), was conducted after approximately 6 months of maintenance treatment. This was followed by an extended maintenance period in subjects tolerating at least 300mg in the DBPCFC where the subjects may be doses at gradually dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks. This analysis set includes events from subjects in the IDE and Updosing periods only.

    Subject analysis set title
    Safety Population Ages 4-17: Group 1 (Maintenance)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during initial dose escalation (IDE; day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 to 300 mg/day for 22 to 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 to 28 weeks). A DBPCFC, using peanut protein (not AR101) of doses up to 2000 mg (4043 mg cumulative), was conducted after approximately 6 months of maintenance treatment. This was followed by an extended maintenance period in subjects tolerating at least 300mg in the DBPCFC where the subjects may be doses at gradually dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks. This analysis set includes event from subjects in the maintenance period only.

    Subject analysis set title
    Safety Population Ages 18-55
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Adult population data not reported.

    Subject analysis sets values
    		 Safety Population Ages 4-17: Group 1 (All Study Periods) Safety Population Ages 4-17: Group 2, Cohort 1 Safety Population Ages 4-17: Group 2, Cohort 2 Safety Population Ages 4-17: Group 2, Cohort 3A Safety Population Ages 4-17: Group 2, Cohort 3B Safety Population Ages 4-17: Group 2, Cohort 3C Safety Population Ages 4-17: Group 1 (IDE and Updosing) Safety Population Ages 4-17: Group 1 (Maintenance) Safety Population Ages 18-55
    Number of subjects
    102
    112
    48
    31
    31
    34
    100
    85
    30
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Children (2-11 years)
    69
    63
    31
    22
    20
    23
    69
    61
    0
        Adolescents (12-17 years)
    33
    46
    15
    9
    11
    11
    31
    24
    0
        Adults (18-64 years)
    0
    0
    0
    0
    0
    0
    0
    0
    30
        From 65-84 years
    0
    0
    0
    0
    0
    0
    0
    0
    0
        85 years and over
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Age continuous
    Subject age at screening (years)
    Units: years
        median (full range (min-max))
    9.5 (5 to 17)
    11 (5 to 17)
    10 (4 to 17)
    9 (5 to 17)
    9 (5 to 16)
    9 (5 to 16)
    Gender categorical
    Units: Subjects
        Female
    37
    52
    22
    14
    12
    16
    35
    30
    12
        Male
    65
    60
    26
    17
    19
    18
    65
    55
    18

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Group 1
    Reporting group description
    		 Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during initial dose escalation (day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 to 300 mg/day for 22 to 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 to 28 weeks). A DBPCFC using peanut protein (not AR101) of doses up to 2000 mg (4043 mg cumulative) was conducted after approximately 6 months of maintenance treatment. This was followed by an extended maintenance period in subjects tolerating at least 300mg in the DBPCFC where the subjects may be dosed at gradually dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks.

    Reporting group title
    Group 2, Cohort 1
    Reporting group description
    		 Group 2, Cohort 1 subjects were the first 120 (approximately) of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day (once daily, QD) for 28 weeks.

    Reporting group title
    Group 2, Cohort 2
    Reporting group description
    		 Group 2, Cohort 2 subjects comprised 50(approximately) of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every other day (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks for a total of 28 weeks.

    Reporting group title
    Group 2, Cohort 3A
    Reporting group description
    		 Group 2, Cohort 3A subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 56 weeks.

    Reporting group title
    Group 2, Cohort 3B
    Reporting group description
    		 Group 2, Cohort 3B subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 28 weeks, 300 mg/day every other (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks (total of 56 weeks).

    Reporting group title
    Group 2, Cohort 3C
    Reporting group description
    		 Group 2, Cohort 3C subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 28 weeks, 300 mg/day every other (QOD) for 4 weeks, twice weekly (BIW) for 24 weeks then once weekly (QW) for 28 weeks (total of 84 weeks).

    Subject analysis set title
    Safety Population Ages 4-17: Group 1 (All Study Periods)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during initial dose escalation (IDE; day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 to 300 mg/day for 22 to 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 to 28 weeks). A DBPCFC, using peanut protein (not AR101) of doses up to 2000 mg (4043 mg cumulative), was conducted after approximately 6 months of maintenance treatment. This was followed by an extended maintenance period in subjects tolerating at least 300mg in the DBPCFC where the subjects may be doses at gradually dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks. This analysis set evaluates all the above study phases. This analysis set includes events from subjects in all study (IDE, Updosing and maintenance) periods.

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 1
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 1 subjects were the first 120 of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day (once daily, QD) for 28 weeks.

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 2
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 2 subjects comprised 50 of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every other day (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks for a total of 28 weeks.

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 3A
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 3A subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 56 weeks.

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 3B
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 3B subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 28 weeks, 300 mg/day every other (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks (total of 56 weeks).

    Subject analysis set title
    Safety Population Ages 4-17: Group 2, Cohort 3C
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Group 2, Cohort 3C subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 4 weeks, 300 mg/day every other (QOD) for 4 weeks, twice weekly (BIW) for 24 weeks then once weekly (QW) for 28 weeks (total of 84 weeks).

    Subject analysis set title
    Safety Population Ages 4-17: Group 1 (IDE and Updosing)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during initial dose escalation (IDE; day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 to 300 mg/day for 22 to 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 to 28 weeks). A DBPCFC, using peanut protein (not AR101) of doses up to 2000 mg (4043 mg cumulative), was conducted after approximately 6 months of maintenance treatment. This was followed by an extended maintenance period in subjects tolerating at least 300mg in the DBPCFC where the subjects may be doses at gradually dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks. This analysis set includes events from subjects in the IDE and Updosing periods only.

    Subject analysis set title
    Safety Population Ages 4-17: Group 1 (Maintenance)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during initial dose escalation (IDE; day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 to 300 mg/day for 22 to 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 to 28 weeks). A DBPCFC, using peanut protein (not AR101) of doses up to 2000 mg (4043 mg cumulative), was conducted after approximately 6 months of maintenance treatment. This was followed by an extended maintenance period in subjects tolerating at least 300mg in the DBPCFC where the subjects may be doses at gradually dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks. This analysis set includes event from subjects in the maintenance period only.

    Subject analysis set title
    Safety Population Ages 18-55
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Adult population data not reported.

    Primary: Overall Summary of Treatment Emergent Adverse Events

    		 Close Top of page
    End point title
    		 Overall Summary of Treatment Emergent Adverse Events [1]
    End point description
    All Treatment Emergent AEs and AEs by Severity
    End point type
    Primary
    End point timeframe
    Group 1: Total duration varies, ranging from approximately 88 to 136 weeks Group 2, Cohort 1: 28 weeks Group 2, Cohort 2: 28 weeks Group 2, Cohort 3A: 56 weeks Group 2, Cohort 3B: 56 weeks Group 2, Cohort 3C: 84 weeks
    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: Data were summarised using descriptive statistics by group/cohort. No specific hypothesis testing or comparisons between treatment groups were performed.
    End point values
    		 Safety Population Ages 4-17: Group 1 (All Study Periods) Safety Population Ages 4-17: Group 2, Cohort 1 Safety Population Ages 4-17: Group 2, Cohort 2 Safety Population Ages 4-17: Group 2, Cohort 3A Safety Population Ages 4-17: Group 2, Cohort 3B Safety Population Ages 4-17: Group 2, Cohort 3C Safety Population Ages 4-17: Group 1 (IDE and Updosing) Safety Population Ages 4-17: Group 1 (Maintenance)
    Number of subjects analysed
    100
    109
    46
    31
    31
    34
    100
    85
    Units: Percentage of Subjects Reporting
    number (not applicable)
        All AEs
    98.0
    82.6
    78.3
    87.1
    90.3
    97.1
    94.0
    89.4
        SAEs
    0
    0.9
    0
    0
    3.2
    2.9
    0
    0
        Grade 1: Mild
    37.0
    53.2
    47.8
    48.4
    41.9
    35.3
    41.0
    52.9
        Grade 2: Moderate
    58.0
    26.6
    30.4
    38.7
    48.4
    52.9
    51.0
    35.3
        Grade 3: Severe
    3.0
    2.8
    0
    0
    0
    8.8
    2.0
    1.2
        Grade 4: Life-Threatening
    0
    0
    0
    0
    0
    0
    0
    0
        Grade 5: Death
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Subjects who tolerated a single dose of 300 mg peanut protein (response rate)

    		 Close Top of page
    End point title
    		 Subjects who tolerated a single dose of 300 mg peanut protein (response rate)
    End point description
    Desensitisation Response Rates at Exit DBPCFC (Completer Population). Maintenance DBPCFC results were used for Group 1 subjects who did not complete the Exit DBPCFC.
    End point type
    Other pre-specified
    End point timeframe
    Group 1: Total duration varies, ranging from approximately 88 to 136 weeks Group 2, Cohort 1: 28 weeks Group 2, Cohort 2: 28 weeks Group 2, Cohort 3A: 56 weeks Group 2, Cohort 3B: 56 weeks Group 2, Cohort 3C: 84 weeks
    End point values
    		 Safety Population Ages 4-17: Group 1 (All Study Periods) Safety Population Ages 4-17: Group 2, Cohort 1 Safety Population Ages 4-17: Group 2, Cohort 2 Safety Population Ages 4-17: Group 2, Cohort 3A Safety Population Ages 4-17: Group 2, Cohort 3B Safety Population Ages 4-17: Group 2, Cohort 3C
    Number of subjects analysed
    72
    103
    38
    26
    22
    21
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Responder %
    98.6 (92.5 to 100)
    98.1 (93.2 to 99.8)
    94.7 (82.3 to 99.4)
    100.0 (86.8 to 100)
    81.8 (59.7 to 94.8)
    90.5 (69.6 to 98.8)
    No statistical analyses for this end point

    Other pre-specified: Subjects who tolerated a single dose of 600 mg peanut protein (response rate)

    		 Close Top of page
    End point title
    		 Subjects who tolerated a single dose of 600 mg peanut protein (response rate)
    End point description
    Desensitisation Response Rates at Exit DBPCFC (Completer Population). Maintenance DBPCFC results were used for Group 1 subjects who did not complete the Exit DBPCFC.
    End point type
    Other pre-specified
    End point timeframe
    Group 1: Total duration varies, ranging from approximately 88 to 136 weeks Group 2, Cohort 1: 28 weeks Group 2, Cohort 2: 28 weeks Group 2, Cohort 3A: 56 weeks Group 2, Cohort 3B: 56 weeks Group 2, Cohort 3C: 84 weeks
    End point values
    		 Safety Population Ages 4-17: Group 1 (All Study Periods) Safety Population Ages 4-17: Group 2, Cohort 1 Safety Population Ages 4-17: Group 2, Cohort 2 Safety Population Ages 4-17: Group 2, Cohort 3A Safety Population Ages 4-17: Group 2, Cohort 3B Safety Population Ages 4-17: Group 2, Cohort 3C
    Number of subjects analysed
    72
    103
    38
    26
    22
    21
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Responder %
    86.1 (75.9 to 93.1)
    89.3 (81.7 to 94.5)
    71.1 (54.1 to 84.6)
    96.2 (80.4 to 99.9)
    77.3 (54.6 to 92.2)
    76.2 (52.8 to 91.8)
    No statistical analyses for this end point

    Other pre-specified: Subjects who tolerated a single dose of 1000 mg peanut protein (response rate)

    		 Close Top of page
    End point title
    		 Subjects who tolerated a single dose of 1000 mg peanut protein (response rate)
    End point description
    Desensitisation Response Rates at Exit DBPCFC (Completer Population). Maintenance DBPCFC results were used for Group 1 subjects who did not complete the Exit DBPCFC.
    End point type
    Other pre-specified
    End point timeframe
    Group 1: Total duration varies, ranging from approximately 88 to 136 weeks Group 2, Cohort 1: 28 weeks Group 2, Cohort 2: 28 weeks Group 2, Cohort 3A: 56 weeks Group 2, Cohort 3B: 56 weeks Group 2, Cohort 3C: 84 weeks
    End point values
    		 Safety Population Ages 4-17: Group 1 (All Study Periods) Safety Population Ages 4-17: Group 2, Cohort 1 Safety Population Ages 4-17: Group 2, Cohort 2 Safety Population Ages 4-17: Group 2, Cohort 3A Safety Population Ages 4-17: Group 2, Cohort 3B Safety Population Ages 4-17: Group 2, Cohort 3C
    Number of subjects analysed
    72
    103
    38
    26
    22
    21
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Responder %
    72.2 (60.4 to 82.1)
    80.6 (71.6 to 87.7)
    57.9 (40.8 to 73.7)
    96.2 (80.4 to 99.9)
    68.2 (45.1 to 86.1)
    66.7 (43.0 to 85.4)
    No statistical analyses for this end point

    Other pre-specified: Subjects who tolerated a single dose of 2000 mg peanut protein (response rate)

    		 Close Top of page
    End point title
    		 Subjects who tolerated a single dose of 2000 mg peanut protein (response rate)
    End point description
    Desensitisation Response Rates at Exit DBPCFC (Completer Population). Maintenance DBPCFC results were used for Group 1 subjects who did not complete the Exit DBPCFC.
    End point type
    Other pre-specified
    End point timeframe
    Group 1: Total duration varies, ranging from approximately 88 to 136 weeks Group 2, Cohort 1: 28 weeks Group 2, Cohort 2: 28 weeks Group 2, Cohort 3A: 56 weeks Group 2, Cohort 3B: 56 weeks Group 2, Cohort 3C: 84 weeks
    End point values
    		 Safety Population Ages 4-17: Group 1 (All Study Periods) Safety Population Ages 4-17: Group 2, Cohort 1 Safety Population Ages 4-17: Group 2, Cohort 2 Safety Population Ages 4-17: Group 2, Cohort 3A Safety Population Ages 4-17: Group 2, Cohort 3B Safety Population Ages 4-17: Group 2, Cohort 3C
    Number of subjects analysed
    72
    103
    38
    26
    22
    21
    Units: Percentage of Subjects
    number (confidence interval 95%)
        Responder %
    51.4 (39.3 to 63.3)
    48.5 (38.6 to 58.6)
    36.8 (21.8 to 54.0)
    80.8 (60.6 to 93.4)
    45.5 (24.4 to 67.8)
    42.9 (21.8 to 66.0)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Group 1: Total duration varies, ranging from approximately 88 to 136 weeks Group 2, Cohort 1: 28 weeks Group 2, Cohort 2: 28 weeks Group 2, Cohort 3A: 56 weeks Group 2, Cohort 3B: 56 weeks Group 2, Cohort 3C: 84 weeks
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Group 1 (Age 4-17)
    Reporting group description
    		 Group 1 (placebo treated subjects in ARC003): Subjects received AR101 during IDE (day 1, 0.5 to 3 or 6 mg; day 2, 3 mg), up dosing (3 300 mg/day for 22 40 weeks, with dose escalations every 2 weeks), and maintenance (300 mg/day for 24 28 weeks). A DBPCFC after approximately 6 months of maintenance treatment evaluated up to a single highest dose of 2000 mg peanut protein food challenge material (4043 mg cumulative) (hereafter, peanut protein when referring to food challenge material; not AR101). Subjects who tolerated a single highest dose of at least 300 mg in the DBPCFC could receive AR101 during extended maintenance in gradually increasing dosing intervals depending on the results from group 2. The total duration of AR101 treatment in group 1 was 88 to 136 weeks.

    Reporting group title
    Group 2, Cohort 1 (Age 4-17)
    Reporting group description
    		 Group 2, Cohort 1 subjects were the first 120 (approximately) of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day (once daily, QD) for 28 weeks.

    Reporting group title
    Group 2, Cohort 2 (Age 4-17)
    Reporting group description
    		 Group 2, Cohort 2 subjects comprised 50(approximately) of the AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every other day (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks for a total of 28 weeks.

    Reporting group title
    Group 2, Cohort 3A (Age 4-17)
    Reporting group description
    		 Group 2, Cohort 3A subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 56 weeks.

    Reporting group title
    Group 2, Cohort 3B (Age 4-17)
    Reporting group description
    		 Group 2, Cohort 3B subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 28 weeks, 300 mg/day every other (QOD) for 4 weeks, then twice weekly (BIW) for 24 weeks (total of 56 weeks).

    Reporting group title
    Group 2, Cohort 3C (Age 4-17)
    Reporting group description
    		 Group 2, Cohort 3C subjects were AR101-treated subjects in ARC003 who tolerated >/= 300 mg peanut protein in the exit DBPCFC. These subjects received 300 mg/day every day (QD) for 4 weeks, 300 mg/day every other (QOD) for 4 weeks, twice weekly (BIW) for 24 weeks then once weekly (QW) for 28 weeks (total of 84 weeks).

    Serious adverse events
    		 Group 1 (Age 4-17) Group 2, Cohort 1 (Age 4-17) Group 2, Cohort 2 (Age 4-17) Group 2, Cohort 3A (Age 4-17) Group 2, Cohort 3B (Age 4-17) Group 2, Cohort 3C (Age 4-17)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 109 (0.92%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 34 (2.94%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 100 (0.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Streptococcal infection
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 109 (0.92%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 100 (0.00%)
    1 / 109 (0.92%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 34 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Group 1 (Age 4-17) Group 2, Cohort 1 (Age 4-17) Group 2, Cohort 2 (Age 4-17) Group 2, Cohort 3A (Age 4-17) Group 2, Cohort 3B (Age 4-17) Group 2, Cohort 3C (Age 4-17)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    98 / 100 (98.00%)
    90 / 109 (82.57%)
    36 / 46 (78.26%)
    27 / 31 (87.10%)
    28 / 31 (90.32%)
    33 / 34 (97.06%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    6 / 100 (6.00%)
    3 / 109 (2.75%)
    2 / 46 (4.35%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 34 (0.00%)
         occurrences all number
    6
    3
    4
    0
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    24 / 100 (24.00%)
    20 / 109 (18.35%)
    4 / 46 (8.70%)
    8 / 31 (25.81%)
    6 / 31 (19.35%)
    13 / 34 (38.24%)
         occurrences all number
    51
    27
    5
    19
    14
    24
    Influenza like illness
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 109 (0.00%)
    1 / 46 (2.17%)
    2 / 31 (6.45%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    2
    0
    1
    2
    0
    2
    Malaise
         subjects affected / exposed
    6 / 100 (6.00%)
    0 / 109 (0.00%)
    2 / 46 (4.35%)
    4 / 31 (12.90%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    10
    0
    3
    4
    0
    2
    Chest pain
         subjects affected / exposed
    9 / 100 (9.00%)
    0 / 109 (0.00%)
    1 / 46 (2.17%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 34 (2.94%)
         occurrences all number
    14
    0
    3
    0
    1
    1
    Fatigue
         subjects affected / exposed
    4 / 100 (4.00%)
    2 / 109 (1.83%)
    1 / 46 (2.17%)
    2 / 31 (6.45%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    4
    2
    1
    2
    0
    1
    Chest discomfort
         subjects affected / exposed
    9 / 100 (9.00%)
    3 / 109 (2.75%)
    0 / 46 (0.00%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
         occurrences all number
    19
    4
    0
    1
    2
    0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    17 / 100 (17.00%)
    7 / 109 (6.42%)
    0 / 46 (0.00%)
    5 / 31 (16.13%)
    2 / 31 (6.45%)
    10 / 34 (29.41%)
         occurrences all number
    22
    13
    0
    14
    2
    13
    Hypersensitivity
         subjects affected / exposed
    6 / 100 (6.00%)
    1 / 109 (0.92%)
    1 / 46 (2.17%)
    5 / 31 (16.13%)
    2 / 31 (6.45%)
    3 / 34 (8.82%)
         occurrences all number
    11
    1
    1
    8
    2
    3
    Seasonal allergy
         subjects affected / exposed
    8 / 100 (8.00%)
    2 / 109 (1.83%)
    0 / 46 (0.00%)
    2 / 31 (6.45%)
    2 / 31 (6.45%)
    1 / 34 (2.94%)
         occurrences all number
    18
    2
    0
    2
    4
    3
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 100 (1.00%)
    2 / 109 (1.83%)
    1 / 46 (2.17%)
    2 / 31 (6.45%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
         occurrences all number
    1
    2
    2
    4
    5
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    44 / 100 (44.00%)
    16 / 109 (14.68%)
    8 / 46 (17.39%)
    8 / 31 (25.81%)
    10 / 31 (32.26%)
    16 / 34 (47.06%)
         occurrences all number
    147
    29
    15
    57
    40
    47
    Throat irritation
         subjects affected / exposed
    32 / 100 (32.00%)
    15 / 109 (13.76%)
    9 / 46 (19.57%)
    5 / 31 (16.13%)
    5 / 31 (16.13%)
    9 / 34 (26.47%)
         occurrences all number
    753
    38
    77
    14
    6
    289
    Oropharyngeal pain
         subjects affected / exposed
    23 / 100 (23.00%)
    7 / 109 (6.42%)
    4 / 46 (8.70%)
    7 / 31 (22.58%)
    6 / 31 (19.35%)
    8 / 34 (23.53%)
         occurrences all number
    82
    9
    8
    28
    11
    12
    Rhinorrhoea
         subjects affected / exposed
    28 / 100 (28.00%)
    7 / 109 (6.42%)
    2 / 46 (4.35%)
    3 / 31 (9.68%)
    4 / 31 (12.90%)
    7 / 34 (20.59%)
         occurrences all number
    65
    23
    19
    15
    10
    22
    Wheezing
         subjects affected / exposed
    17 / 100 (17.00%)
    3 / 109 (2.75%)
    2 / 46 (4.35%)
    2 / 31 (6.45%)
    2 / 31 (6.45%)
    7 / 34 (20.59%)
         occurrences all number
    54
    5
    5
    12
    3
    10
    Asthma
         subjects affected / exposed
    4 / 100 (4.00%)
    3 / 109 (2.75%)
    4 / 46 (8.70%)
    0 / 31 (0.00%)
    4 / 31 (12.90%)
    6 / 34 (17.65%)
         occurrences all number
    5
    3
    12
    0
    7
    8
    Nasal congestion
         subjects affected / exposed
    22 / 100 (22.00%)
    8 / 109 (7.34%)
    6 / 46 (13.04%)
    2 / 31 (6.45%)
    4 / 31 (12.90%)
    6 / 34 (17.65%)
         occurrences all number
    61
    13
    8
    37
    15
    14
    Dyspnoea
         subjects affected / exposed
    12 / 100 (12.00%)
    1 / 109 (0.92%)
    1 / 46 (2.17%)
    3 / 31 (9.68%)
    5 / 31 (16.13%)
    5 / 34 (14.71%)
         occurrences all number
    57
    2
    2
    5
    5
    7
    Sneezing
         subjects affected / exposed
    18 / 100 (18.00%)
    8 / 109 (7.34%)
    4 / 46 (8.70%)
    3 / 31 (9.68%)
    4 / 31 (12.90%)
    4 / 34 (11.76%)
         occurrences all number
    54
    24
    5
    7
    14
    11
    Pharyngeal paraesthesia
         subjects affected / exposed
    2 / 100 (2.00%)
    0 / 109 (0.00%)
    1 / 46 (2.17%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    3 / 34 (8.82%)
         occurrences all number
    2
    0
    1
    0
    1
    5
    Rhinitis allergic
         subjects affected / exposed
    7 / 100 (7.00%)
    3 / 109 (2.75%)
    3 / 46 (6.52%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    2 / 34 (5.88%)
         occurrences all number
    48
    4
    3
    0
    2
    2
    Throat tightness
         subjects affected / exposed
    12 / 100 (12.00%)
    1 / 109 (0.92%)
    1 / 46 (2.17%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    26
    2
    2
    0
    2
    2
    Productive cough
         subjects affected / exposed
    2 / 100 (2.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    2 / 31 (6.45%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
         occurrences all number
    3
    0
    0
    4
    2
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    4 / 100 (4.00%)
    1 / 109 (0.92%)
    0 / 46 (0.00%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    3 / 34 (8.82%)
         occurrences all number
    6
    1
    0
    1
    1
    4
    Arthropod sting
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    Procedural pain
         subjects affected / exposed
    2 / 100 (2.00%)
    1 / 109 (0.92%)
    1 / 46 (2.17%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    1 / 34 (2.94%)
         occurrences all number
    2
    1
    1
    1
    4
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    27 / 100 (27.00%)
    12 / 109 (11.01%)
    12 / 46 (26.09%)
    8 / 31 (25.81%)
    5 / 31 (16.13%)
    14 / 34 (41.18%)
         occurrences all number
    69
    22
    22
    19
    12
    51
    Dizziness
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 109 (0.00%)
    1 / 46 (2.17%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    1
    0
    1
    0
    0
    2
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    2 / 100 (2.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    2 / 34 (5.88%)
         occurrences all number
    3
    0
    0
    0
    3
    2
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    3 / 100 (3.00%)
    1 / 109 (0.92%)
    0 / 46 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    3 / 34 (8.82%)
         occurrences all number
    5
    1
    0
    1
    0
    4
    Ear pruritus
         subjects affected / exposed
    2 / 100 (2.00%)
    1 / 109 (0.92%)
    3 / 46 (6.52%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    3
    3
    9
    1
    0
    2
    Eye disorders
    Eye pruritus
         subjects affected / exposed
    8 / 100 (8.00%)
    5 / 109 (4.59%)
    4 / 46 (8.70%)
    1 / 31 (3.23%)
    3 / 31 (9.68%)
    6 / 34 (17.65%)
         occurrences all number
    16
    6
    4
    1
    4
    36
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    38 / 100 (38.00%)
    11 / 109 (10.09%)
    7 / 46 (15.22%)
    5 / 31 (16.13%)
    7 / 31 (22.58%)
    16 / 34 (47.06%)
         occurrences all number
    315
    22
    13
    43
    14
    95
    Vomiting
         subjects affected / exposed
    42 / 100 (42.00%)
    18 / 109 (16.51%)
    6 / 46 (13.04%)
    6 / 31 (19.35%)
    9 / 31 (29.03%)
    9 / 34 (26.47%)
         occurrences all number
    116
    32
    10
    8
    21
    25
    Oral pruritus
         subjects affected / exposed
    17 / 100 (17.00%)
    6 / 109 (5.50%)
    5 / 46 (10.87%)
    4 / 31 (12.90%)
    3 / 31 (9.68%)
    7 / 34 (20.59%)
         occurrences all number
    354
    232
    40
    10
    9
    16
    Nausea
         subjects affected / exposed
    33 / 100 (33.00%)
    9 / 109 (8.26%)
    9 / 46 (19.57%)
    5 / 31 (16.13%)
    5 / 31 (16.13%)
    5 / 34 (14.71%)
         occurrences all number
    241
    15
    14
    5
    9
    12
    Abdominal pain upper
         subjects affected / exposed
    31 / 100 (31.00%)
    9 / 109 (8.26%)
    6 / 46 (13.04%)
    5 / 31 (16.13%)
    6 / 31 (19.35%)
    4 / 34 (11.76%)
         occurrences all number
    223
    136
    75
    28
    10
    8
    Lip pruritus
         subjects affected / exposed
    11 / 100 (11.00%)
    3 / 109 (2.75%)
    2 / 46 (4.35%)
    2 / 31 (6.45%)
    3 / 31 (9.68%)
    4 / 34 (11.76%)
         occurrences all number
    88
    4
    12
    4
    13
    31
    Lip swelling
         subjects affected / exposed
    8 / 100 (8.00%)
    3 / 109 (2.75%)
    4 / 46 (8.70%)
    3 / 31 (9.68%)
    2 / 31 (6.45%)
    4 / 34 (11.76%)
         occurrences all number
    11
    3
    5
    16
    2
    24
    Paraesthesia oral
         subjects affected / exposed
    6 / 100 (6.00%)
    0 / 109 (0.00%)
    2 / 46 (4.35%)
    2 / 31 (6.45%)
    2 / 31 (6.45%)
    4 / 34 (11.76%)
         occurrences all number
    62
    0
    2
    2
    3
    237
    Abdominal discomfort
         subjects affected / exposed
    17 / 100 (17.00%)
    6 / 109 (5.50%)
    5 / 46 (10.87%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    3 / 34 (8.82%)
         occurrences all number
    46
    20
    20
    0
    5
    4
    Diarrhoea
         subjects affected / exposed
    10 / 100 (10.00%)
    5 / 109 (4.59%)
    1 / 46 (2.17%)
    4 / 31 (12.90%)
    4 / 31 (12.90%)
    2 / 34 (5.88%)
         occurrences all number
    67
    11
    4
    15
    9
    3
    Tongue pruritus
         subjects affected / exposed
    11 / 100 (11.00%)
    3 / 109 (2.75%)
    1 / 46 (2.17%)
    2 / 31 (6.45%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    114
    5
    6
    3
    0
    43
    Toothache
         subjects affected / exposed
    5 / 100 (5.00%)
    0 / 109 (0.00%)
    1 / 46 (2.17%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    5
    0
    2
    2
    0
    2
    Oral discomfort
         subjects affected / exposed
    1 / 100 (1.00%)
    1 / 109 (0.92%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    1 / 34 (2.94%)
         occurrences all number
    5
    1
    0
    0
    4
    1
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    37 / 100 (37.00%)
    16 / 109 (14.68%)
    6 / 46 (13.04%)
    7 / 31 (22.58%)
    6 / 31 (19.35%)
    9 / 34 (26.47%)
         occurrences all number
    96
    32
    12
    34
    9
    19
    Pruritus
         subjects affected / exposed
    19 / 100 (19.00%)
    7 / 109 (6.42%)
    6 / 46 (13.04%)
    1 / 31 (3.23%)
    7 / 31 (22.58%)
    5 / 34 (14.71%)
         occurrences all number
    47
    11
    10
    2
    8
    12
    Rash
         subjects affected / exposed
    14 / 100 (14.00%)
    6 / 109 (5.50%)
    1 / 46 (2.17%)
    1 / 31 (3.23%)
    3 / 31 (9.68%)
    5 / 34 (14.71%)
         occurrences all number
    16
    6
    1
    1
    3
    6
    Eczema
         subjects affected / exposed
    7 / 100 (7.00%)
    2 / 109 (1.83%)
    1 / 46 (2.17%)
    2 / 31 (6.45%)
    3 / 31 (9.68%)
    3 / 34 (8.82%)
         occurrences all number
    10
    2
    1
    4
    4
    3
    Dermatitis atopic
         subjects affected / exposed
    3 / 100 (3.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    3
    0
    0
    0
    0
    9
    Swelling face
         subjects affected / exposed
    1 / 100 (1.00%)
    1 / 109 (0.92%)
    1 / 46 (2.17%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    1
    1
    1
    1
    0
    2
    Erythema
         subjects affected / exposed
    8 / 100 (8.00%)
    1 / 109 (0.92%)
    1 / 46 (2.17%)
    1 / 31 (3.23%)
    3 / 31 (9.68%)
    1 / 34 (2.94%)
         occurrences all number
    26
    1
    1
    1
    7
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 100 (2.00%)
    2 / 109 (1.83%)
    0 / 46 (0.00%)
    2 / 31 (6.45%)
    1 / 31 (3.23%)
    1 / 34 (2.94%)
         occurrences all number
    2
    2
    0
    2
    1
    2
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    16 / 100 (16.00%)
    5 / 109 (4.59%)
    5 / 46 (10.87%)
    5 / 31 (16.13%)
    5 / 31 (16.13%)
    9 / 34 (26.47%)
         occurrences all number
    31
    9
    7
    5
    7
    18
    Upper respiratory tract infection
         subjects affected / exposed
    23 / 100 (23.00%)
    20 / 109 (18.35%)
    6 / 46 (13.04%)
    3 / 31 (9.68%)
    5 / 31 (16.13%)
    7 / 34 (20.59%)
         occurrences all number
    49
    27
    7
    7
    11
    17
    Sinusitis
         subjects affected / exposed
    6 / 100 (6.00%)
    2 / 109 (1.83%)
    1 / 46 (2.17%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    4 / 34 (11.76%)
         occurrences all number
    8
    2
    1
    0
    1
    4
    Viral infection
         subjects affected / exposed
    10 / 100 (10.00%)
    9 / 109 (8.26%)
    1 / 46 (2.17%)
    5 / 31 (16.13%)
    1 / 31 (3.23%)
    4 / 34 (11.76%)
         occurrences all number
    13
    12
    1
    7
    1
    11
    Conjunctivitis
         subjects affected / exposed
    4 / 100 (4.00%)
    1 / 109 (0.92%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    3 / 34 (8.82%)
         occurrences all number
    5
    1
    0
    0
    0
    3
    Gastroenteritis
         subjects affected / exposed
    5 / 100 (5.00%)
    2 / 109 (1.83%)
    1 / 46 (2.17%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    3 / 34 (8.82%)
         occurrences all number
    5
    2
    1
    0
    4
    5
    Influenza
         subjects affected / exposed
    7 / 100 (7.00%)
    7 / 109 (6.42%)
    1 / 46 (2.17%)
    1 / 31 (3.23%)
    5 / 31 (16.13%)
    3 / 34 (8.82%)
         occurrences all number
    8
    7
    1
    1
    5
    3
    Rhinitis
         subjects affected / exposed
    6 / 100 (6.00%)
    1 / 109 (0.92%)
    0 / 46 (0.00%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    3 / 34 (8.82%)
         occurrences all number
    11
    1
    0
    3
    1
    4
    Gastrointestinal viral infection
         subjects affected / exposed
    2 / 100 (2.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    2
    0
    0
    0
    0
    2
    Tonsillitis
         subjects affected / exposed
    2 / 100 (2.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    2
    0
    0
    1
    0
    2
    Gastroenteritis viral
         subjects affected / exposed
    9 / 100 (9.00%)
    7 / 109 (6.42%)
    1 / 46 (2.17%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    1 / 34 (2.94%)
         occurrences all number
    12
    7
    1
    0
    3
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    4 / 100 (4.00%)
    5 / 109 (4.59%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    1 / 34 (2.94%)
         occurrences all number
    4
    6
    0
    0
    2
    1
    Ear infection
         subjects affected / exposed
    2 / 100 (2.00%)
    4 / 109 (3.67%)
    3 / 46 (6.52%)
    3 / 31 (9.68%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
         occurrences all number
    2
    5
    3
    6
    1
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    4 / 100 (4.00%)
    5 / 109 (4.59%)
    5 / 46 (10.87%)
    3 / 31 (9.68%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
         occurrences all number
    4
    5
    8
    4
    1
    0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 100 (1.00%)
    0 / 109 (0.00%)
    0 / 46 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    0 / 34 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Oct 2016
    • Text and schematic modified to clarify procedures.
    07 Feb 2017
    • Changed the up dosing period duration from 20 to 40 weeks to 22 to 40 weeks for accuracy based on the dosing intervals. • Defined severe adverse events and adverse events associated with epinephrine use as adverse events of clinical interest. • Added: o a 4 week QOD dosing interval before transitioning to BIW dosing. o instructions for adjusting doses and managing missed doses for nondaily dosing regimens. o an allowance for screening procedures to be performed over 3 consecutive days o instructions for reporting an accidental food allergen exposure. o rationale and formula for cohort stopping rules. o that an adjudication committee will be used in the safety monitoring committee. • Text modified to clarify procedures.
    12 Jun 2017
    • Changed the interval extension periods for group 1 extended maintenance from 8 to 24 weeks to 8 to 28 weeks. • Added: o instructions for repeat up dosing for group 2 subjects who did not tolerate nondaily dosing. o guidelines for modifying QD dosing for group 1. o guidance for continuation of treatment for subjects with severe symptoms. o requirement to counsel and provide contraception information to postmenarchal subjects. o both parents must sign the informed consent form when required. o study product shipment and dispensation information. o subjects should not administer AR101 on the day of the DBPCFC. o end of study definition. • Text modified to clarify procedures.
    05 Mar 2018
    • Text modified to clarify procedures.
    12 Apr 2018
    • Added a maximum 26 week requirement for completion of repeat up dosing. • Text modified to clarify procedures and correct discrepancies.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 03:35:20 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA