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:
    A Dose Finding Study of the Efficacy of LAIS® Mites Sublingual tablets in patients suffering from house dust mite-induced allergic rhinoconjunctivitis A prospective, double-blind, placebo-controlled randomized multi-centre trial.

    Summary
    EudraCT number
    		 2013-000617-20
    Trial protocol
    		 DE  
    Global end of trial date
    13 May 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Oct 2021
    First version publication date
    27 Oct 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SMART_2
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Lofarma Spa
    Sponsor organisation address
    Viale Cassala, 40, Milan, Italy, 20143
    Public contact
    Scientific Director Lofarma SPA, Institut für Med. Statistik, Informatik u. Epidemiologie, +39 0258198287,
    Scientific contact
    Scientific Director Lofarma SPA, Institut für Med. Statistik, Informatik u. Epidemiologie, +39 0258198287,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    13 May 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 May 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The efficacy of sublingual immunotherapy with the allergoid LAIS® Mites Sublingual tablets will be assessed by the mean improvement in the allergic severity S between baseline and visit V4, comparing the five treatment groups. Allergic severity S is rated by means of the severity stage integer values 0 ≤ ci ≤ 4. Here i is a number of an attempt (titration stage), made to reach a positive allergic reaction within the Conjunctival Provocation Test (CPT). CPT is considered positive if the response is stage 2 or higher. The maximum number of attempts (N) is restricted with the titration solutions available. If the severity stage is reached to be ci= 2, the CPT is considered as positive, the test is stopped for the current visit and N is the number of steps to reach a positive result (1, 2, 3). The titrated conjunctival allergen challenge will be conducted with solutions containing 100, 1,000 and 10,000 SQ-E/ml mite allergens.
    Protection of trial subjects
    Before including a patient, the investigator informed the patient in his own words of the nature of the trial, of its aims, of the methods and means to be used, and of the estimated duration of the study. He/she had also informed the patient of the possible risks linked with administration of the products and of the possible effects which to his/her knowledge might occur. Moreover, the main procedures used to guarantee the subjects’ anonymity especially during the analysis of their personal data were profoundly explained. The patient was allowed to ask questions and had to be satisfied with all the investigator´s answers. Before asking the patient to sign the consent form, the investigator ascertained that the patient entirely understood and agreed to all information provided. The subject was free to withdraw from the study at any time without prejudicing future medical care and giving a reason. If any new information became available that might have influenced the subject’s decision to stay in the trial, it was transmitted without delay to the subject.
    Background therapy
    		 All patients were supplied with a blister of an oral antihistamine (10 mg Loratadine) to be taken on demand as rescue medication for potentially appearing local side effects like oral pruritus and edema of mouth, tongue or lips.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Aug 2013
    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
    Germany: 165
    Worldwide total number of subjects
    165
    EEA total number of subjects
    165
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    165
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 It was planned to recruit 150 patients in total, with 30 participants in each treatment group. However, a total number of 165 patients were screened, 131 patients were randomized, with 127 being valid for the ITT analysis subset.

    Pre-assignment
    Screening details
    		 Female or male patients aged 18–75 years with a history of at least two years of house dust mites (HDM) induced allergic rhinitis and/or allergic rhinoconjunctivitis with or without controlled asthma upon exposure to house dust mites [From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2012]

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    Placebo and verum preparations were identical except of the active substances. i.e. carbamylated, monomeric allergoids of mite.

    Arm title
    		 LAIS® Mites 300 UA/Day
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    LAIS® Mites 300 Ua/Day
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    The treatment was randomly allocated to a subject. Each subjects treatment was scheduled for 12 weeks (84±7 days) and each subject ingested one sublingual tablet per day independent of the assigned group. The participants were instructed to place the tablet under the tongue and dissolved for two minutes before swallowing. The first application (day 0) was performed under supervision and the patients remained under the observation of a trained allergologist for at least 30 minutes. Afterwards, trial medication was handed to the patients and administered by him- / herself.

    Arm title
    		 Lais Mites 1,000 UA/day
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    LAIS® Mites 1,000 UA/day
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    The treatment was randomly allocated to a subject. Each subjects treatment was scheduled for 12 weeks (84±7 days) and each subject ingested one sublingual tablet per day independent of the assigned group. The participants were instructed to place the tablet under the tongue and dissolved for two minutes before swallowing. The first application (day 0) was performed under supervision and the patients remained under the observation of a trained allergologist for at least 30 minutes. Afterwards, trial medication was handed to the patients and administered by him- / herself.

    Arm title
    		 LAIS® Mites 2,000 UA/Day
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    LAIS® Mites 2,000 UA/Day
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    The treatment was randomly allocated to a subject. Each subjects treatment was scheduled for 12 weeks (84±7 days) and each subject ingested one sublingual tablet per day independent of the assigned group. The participants were instructed to place the tablet under the tongue and dissolved for two minutes before swallowing. The first application (day 0) was performed under supervision and the patients remained under the observation of a trained allergologist for at least 30 minutes. Afterwards, trial medication was handed to the patients and administered by him- / herself.

    Arm title
    		 LAIS® Mites 3,000 UA/Day
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    LAIS® Mites Sublingual 3,000 UA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sublingual tablet
    Routes of administration
    Sublingual use
    Dosage and administration details
    The treatment was randomly allocated to a subject. Each subjects treatment was scheduled for 12 weeks (84±7 days) and each subject ingested one sublingual tablet per day independent of the assigned group. The participants were instructed to place the tablet under the tongue and dissolved for two minutes before swallowing. The first application (day 0) was performed under supervision and the patients remained under the observation of a trained allergologist for at least 30 minutes. Afterwards, trial medication was handed to the patients and administered by him- / herself.

    Number of subjects in period 1 [1]
    		Placebo LAIS® Mites 300 UA/Day Lais Mites 1,000 UA/day LAIS® Mites 2,000 UA/Day LAIS® Mites 3,000 UA/Day
    Started
    29
    23
    27
    26
    26
    Completed
    28
    23
    26
    26
    25
    Not completed
    1
    0
    1
    0
    1
         Consent withdrawn by subject
    -
    -
    1
    -
    1
         Adverse event, non-fatal
    1
    -
    -
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Since 34 patients resulted as screening failures, 131 patients were randomized into this study.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Lais Mites
    Reporting group description
    		 -

    Reporting group values
    		 Lais Mites Total
    Number of subjects
    		 131 131
    Age categorical
    Units: Subjects
        Adults (18–75 years)
    		 131 131
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 37.48 (18 to 70) -
    Gender categorical
    Units: Subjects
        Female
    		 64 64
        Male
    		 67 67
    Subject analysis sets

    Subject analysis set title
    Safety set (S-set)/ Exposed Subjects
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    randomized subjects who have been exposed to the study medication at least once. Only safety analyses will be performed in this group.

    Subject analysis set title
    Intention-To-Treat-set (ITT-set)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Randomized subjects who meet key eligibility and evaluability criteria. This dataset is defined by the existence of evaluable CPT data at baseline and V3 or later.

    Subject analysis set title
    Per-Protocol-set (PP-set)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    evaluable subjects who comply with the protocol in all points, delivering a complete data set of measurements and evaluations of the primary efficacy variable. A maximum of 25 % deviation from the planned intake of study medication was accepted as per protocol drug intake

    Subject analysis set title
    Randomized
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all subjects randomized into the study.

    Subject analysis sets values
    		 Safety set (S-set)/ Exposed Subjects Intention-To-Treat-set (ITT-set) Per-Protocol-set (PP-set) Randomized
    Number of subjects
    131
    127
    119
    131
    Age categorical
    Units: Subjects
        Adults (18–75 years)
    131
    127
    119
    131
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    37.48 (18 to 70)
    37.48 (18 to 70)
    37.44 (18 to 70)
    37.48 (18 to 70)
    Gender categorical
    Units: Subjects
        Female
    64
    63
    59
    64
        Male
    67
    64
    60
    67

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    LAIS® Mites 300 UA/Day
    Reporting group description
    		 -

    Reporting group title
    Lais Mites 1,000 UA/day
    Reporting group description
    		 -

    Reporting group title
    LAIS® Mites 2,000 UA/Day
    Reporting group description
    		 -

    Reporting group title
    LAIS® Mites 3,000 UA/Day
    Reporting group description
    		 -

    Subject analysis set title
    Safety set (S-set)/ Exposed Subjects
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    randomized subjects who have been exposed to the study medication at least once. Only safety analyses will be performed in this group.

    Subject analysis set title
    Intention-To-Treat-set (ITT-set)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Randomized subjects who meet key eligibility and evaluability criteria. This dataset is defined by the existence of evaluable CPT data at baseline and V3 or later.

    Subject analysis set title
    Per-Protocol-set (PP-set)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    evaluable subjects who comply with the protocol in all points, delivering a complete data set of measurements and evaluations of the primary efficacy variable. A maximum of 25 % deviation from the planned intake of study medication was accepted as per protocol drug intake

    Subject analysis set title
    Randomized
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all subjects randomized into the study.

    Primary: Efficacy (allergic severity score S)

    		 Close Top of page
    End point title
    		 Efficacy (allergic severity score S)
    End point description
    The primary outcome parameter of the study was the improvement of the allergic severity S between baseline and V4 (day 84 ± 7). There was a distinct improvement of the allergic severity S between baseline and V3 and a more pronounced improvement between baseline and V4 in each study arm
    End point type
    Primary
    End point timeframe
    between baseline and visit V4.
    End point values
    		 Placebo LAIS® Mites 300 UA/Day Lais Mites 1,000 UA/day LAIS® Mites 2,000 UA/Day LAIS® Mites 3,000 UA/Day
    Number of subjects analysed
    28
    23
    25
    26
    25
    Units: Score
    arithmetic mean (standard deviation)
        D Baseline - V4
    0.30 ± 0.501
    0.21 ± 0.373
    0.37 ± 0.735
    0.33 ± 0.462
    0.27 ± 0.475
        Mean Severity at V4
    0.29 ± 0.50
    0.14 ± 0.17
    0.15 ± 0.13
    0.10 ± 0.10
    0.15 ± 0.09
    Statistical analysis title
    		 Placebo vs. 300 UA
    Comparison groups
    Placebo v LAIS® Mites 300 UA/Day
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.251
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 Placebo vs. 1,000 UA
    Comparison groups
    Placebo v Lais Mites 1,000 UA/day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.706
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 Placebo vs. 2,000 UA
    Statistical analysis description
    In summary, the mean relative improvement of the allergic severity S was highest in the 2,000 UA/d-group (66,8%) with p<0.1 compared to the placebo group. Additionally, the percentage of patients with improved allergic severity between baseline and V4 was the highest in the treatment group with a daily dose of 2,000 UA. Therefore, the results of this clinical trial clearly demonstrated a general efficacy of the treatment with LAIS® mites tablets of 2,000 UA.
    Comparison groups
    Placebo v LAIS® Mites 2,000 UA/Day
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.093
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [1] - The largest amount of patients having improved in the allergic severity S were in the group having received 2,000 UA/d (88,5%) (Table 14.1.5.1.2.2, Figure 11.3). However, comparing the proportion of patients with improvement of the allergic severity S of the placebo group and the actively treated groups statistical significance was not observed.
    Statistical analysis title
    		 Placebo vs. 3,000 UA
    Comparison groups
    LAIS® Mites 3,000 UA/Day v Placebo
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.878
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 Mean Severity at V4 2000 UA
    Statistical analysis description
    The primary efficacy outcome parameter was the change in the allergic severity between baseline and the final visit V4, calculated from the reaction to the CPT
    Comparison groups
    LAIS® Mites 2,000 UA/Day v Placebo v LAIS® Mites 300 UA/Day v Lais Mites 1,000 UA/day v LAIS® Mites 3,000 UA/Day
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 < 0.1 [3]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [2] - In the present study, the analysis of the CPT results by means of S (13) favours the active treatment dose of 2000 UA/day when compared to placebo. Likewise, the percentage of patients having an improved CPT threshold at the final visit is significantly higher in the group treated with 2000 UA/day than in the placebo group.
    [3] - the mean S in the four active treatment groups was only one-third to one-half of the mean S in the placebo, favouring the treatment group 2000 UA/day, although not significant (P < 0.1)

    Secondary: CPT Result Score

    		 Close Top of page
    End point title
    		 CPT Result Score
    End point description
    As a secondary objective, the changes of the threshold allergen concentration for a positive CPT between baseline and V3 as well as between baseline and V4 were analyzed by means of a CPT result score
    End point type
    Secondary
    End point timeframe
    Baseline - v3 Baseline - v4
    End point values
    		 Placebo LAIS® Mites 300 UA/Day Lais Mites 1,000 UA/day LAIS® Mites 2,000 UA/Day LAIS® Mites 3,000 UA/Day
    Number of subjects analysed
    28
    23
    25
    26
    25
    Units: Score
    arithmetic mean (standard deviation)
        D Baseline - V3
    0.54 ± 0.744
    0.43 ± 0.728
    0.64 ± 0.810
    0.65 ± 0.846
    0.28 ± 0.678
        D Baseline - V4
    0.86 ± 0.932
    0.78 ± 0.671
    0.88 ± 0.927
    1.15 ± 0.675
    0.96 ± 0.735
    Statistical analysis title
    		 CPT baseline - V3 Placebo VS 300UA
    Comparison groups
    Placebo v LAIS® Mites 300 UA/Day
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.908
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 CPT baseline - V3 Placebo VS 1,000UA
    Comparison groups
    Placebo v Lais Mites 1,000 UA/day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.476
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 CPT baseline - V3 Placebo VS 2,000UA
    Comparison groups
    Placebo v LAIS® Mites 2,000 UA/Day
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.496
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 CPT baseline - V3 Placebo VS 3,000UA
    Comparison groups
    Placebo v LAIS® Mites 3,000 UA/Day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.38
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 CPT baseline - V4 Placebo VS 300UA
    Comparison groups
    Placebo v LAIS® Mites 300 UA/Day
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.958
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 CPT baseline - V4 Placebo VS 1,000UA
    Comparison groups
    Placebo v Lais Mites 1,000 UA/day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.76
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 CPT baseline - V4 Placebo VS 3,000UA
    Comparison groups
    Placebo v LAIS® Mites 3,000 UA/Day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.544
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 n° Pt improved CPT Placebo Vs 300UA baseline - V3
    Statistical analysis description
    number of patients with improved CPT response threshold between actively treated and placebo group
    Comparison groups
    Placebo v LAIS® Mites 300 UA/Day
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.725
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 n° Pt improved CPT Placebo Vs 1,000UA baseline-V3
    Statistical analysis description
    number of patients with improved CPT response threshold between actively treated and placebo group
    Comparison groups
    Placebo v Lais Mites 1,000 UA/day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.344
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 n° Pt improved CPT Placebo Vs 2,000UA baseline-V3
    Statistical analysis description
    number of patients with improved CPT response threshold between actively treated and placebo group
    Comparison groups
    Placebo v LAIS® Mites 2,000 UA/Day
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.424
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 n° Pt improved CPT Placebo Vs 3,000UA baseline-V3
    Statistical analysis description
    number of patients with improved CPT response threshold between actively treated and placebo group
    Comparison groups
    Placebo v LAIS® Mites 3,000 UA/Day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.835
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 n° Pt improved CPT Placebo Vs 300UA baseline - V4
    Comparison groups
    Placebo v LAIS® Mites 300 UA/Day
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.465
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 n° Pt improved CPT Placebo Vs 1,000UA baseline-V4
    Comparison groups
    Placebo v Lais Mites 1,000 UA/day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.358
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 n° Pt improved CPT Placebo Vs 2,000UA baseline-V4
    Comparison groups
    Placebo v LAIS® Mites 2,000 UA/Day
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.04 [5]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [4] - The rate of patients who had a worse or unchanged CPT response threshold between baseline and V4 was the lowest (11.5%) in the 2,000 UA/d-group.
    [5] - Also, the maximum effect was achieved with a daily dose of 2,000 UA, while higher or lower doses showed less efficacy.
    Statistical analysis title
    		 n° Pt improved CPT Placebo Vs 3,000UA baseline-V4
    Comparison groups
    Placebo v LAIS® Mites 3,000 UA/Day
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.358 [6]
    Method
    		 t-test, 2-sided
    Confidence interval
    Notes
    [6] - Also, the maximum effect was achieved with a daily dose of 2,000 UA, while higher or lower doses showed less efficacy.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    The treatment lasted from the 3rd quarter 2013 to the 2nd quarter 2014. The study protocol defined a treatment duration of 84 ± 7 days. Finally, the minimum of treatment duration (V1-V4) was 56 days and the the maximum duration was 105 days.
    Adverse event reporting additional description
    Of 131 patients in the safety analysis set, 37 patients (28%) reported a total number of 50 treatment emerged adverse events (AEs), of which one was a serious adverse event (SAE). The SAE was recorded as a mamma carcinoma in one patient of the placebo group. These numbers are identical for both ITT and safety analysis sets.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    nk
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    LAIS® Mites 300 UA/Day
    Reporting group description
    		 -

    Reporting group title
    Lais Mites 1,000 UA/day
    Reporting group description
    		 -

    Reporting group title
    LAIS® Mites 2,000 UA/Day
    Reporting group description
    		 -

    Reporting group title
    LAIS® Mites 3,000 UA/Day
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo LAIS® Mites 300 UA/Day Lais Mites 1,000 UA/day LAIS® Mites 2,000 UA/Day LAIS® Mites 3,000 UA/Day
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo LAIS® Mites 300 UA/Day Lais Mites 1,000 UA/day LAIS® Mites 2,000 UA/Day LAIS® Mites 3,000 UA/Day
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 29 (20.69%)
    9 / 23 (39.13%)
    6 / 27 (22.22%)
    7 / 26 (26.92%)
    9 / 26 (34.62%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer female
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    0
    0
    1
    Weight increased
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Gastroenteritis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    0
    0
    1
    Sensation of pressure
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Ear and labyrinth disorders
    Ear pruritus
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    0
    0
    1
    Gastritis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Oral discomfort
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    2
    0
    1
    Glossodynia
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    0
    0
    1
    Oral pruritus
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Hypoaesthesia oral
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Swollen tongue
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Oropharyngeal swelling
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nasal discomfort
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    2 / 26 (7.69%)
    2 / 26 (7.69%)
         occurrences all number
    0
    0
    0
    2
    4
    Epistaxis
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    0
    0
    1
    Oropharyngeal blistering
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Wheezing
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    Sneezing
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    1 / 27 (3.70%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Increased upper airway secretion
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Throat irritation
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Renal and urinary disorders
    Cystitis noninfective
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 23 (4.35%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Viral infection
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 23 (8.70%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 23 (8.70%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    0
    0
    2
    Acute sinusitis
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    3 / 26 (11.54%)
    3 / 26 (11.54%)
         occurrences all number
    0
    0
    0
    3
    3
    Pulpitis dental
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    0
    0
    1
    Herpes virus infection
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 23 (0.00%)
    0 / 27 (0.00%)
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    0
    0
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Jan 2014
    In the initial version of the study protocol (version 2.0), it was specified that the specific CAP-RAST results to co-allergens had to be less than the CAP-RAST result to mite allergens (the difference had to be ≥ 1) and the results of the skin prick test against co-allergens had to be less than the result of the skin prick test against mite allergens. Allergy against mugwort, alternaria and ambrosia were regarded as exclusion criteria. The final study protocol version 4.1 provided that patients with co-sensitizations to aero-allergens like grass or rye, could be included into the trial irrespective of the skin prick test results. Patients with co-sensitizations against perennial allergens like cat or dog dander could also be included irrespective of the skin prick test results, as long as they were not regularly exposed to these allergens and therefore show no symptoms. Allergy against mugwort, ambrosia and alternaria did not represent an exclusion criterion according to this new version of the study protocol.

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/27068870
    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-Mon May 06 11:35:50 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA