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    The EU Clinical Trials Register currently displays   36119   clinical trials with a EudraCT protocol, of which   5940   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2013-003732-72
    Sponsor's Protocol Code Number:13IC0847
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-10-14
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2013-003732-72
    A.3Full title of the trial
    Randomised placebo-controlled study of grass pollen allergen immunotherapy tablet (AIT) for seasonal rhinitis: time course of nasal, cutaneous and immunological outcomes
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of effects of grass pollen allergen immunotherapy tablet (AIT) for hay fever
    A.3.2Name or abbreviated title of the trial where available
    Grass Pollen Allergen Immunotherapy Tablet (AIT) Time Course Study
    A.4.1Sponsor's protocol code number13IC0847
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorImperial College London
    B.1.3.4Country
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportALK Abello, Horsholm - Supply of IMP and placebo
    B.4.2CountryDenmark
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationImperial College London
    B.5.2Functional name of contact pointNabila Youssouf
    B.5.3 Address:
    B.5.3.1Street AddressJoint Research Office
    B.5.3.2Town/ cityImperial College and Imperial College Healthcare
    B.5.3.3Post codeW6 8RF
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02033110206
    B.5.5Fax number02033110203
    B.5.6E-mailnabila.youssouf08@imperial.ac.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name GRAZAX 75,000 SQ-T oral lyophilisate
    D.2.1.1.2Name of the Marketing Authorisation holderALK Abello S/A
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGrazax
    D.3.4Pharmaceutical form Oral lyophilisate
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSublingual use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.4EV Substance CodeAS1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboOral lyophilisate
    D.8.4Route of administration of the placeboSublingual use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Grass-pollen induced rhinoconjunctivitis (hay fever).
    E.1.1.1Medical condition in easily understood language
    Hay fever
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To understand the time course of clinical and immunological actions of grass pollen allergen immunotherapy tablets in the treatment of seasonal allergic rhinitis.
    E.2.2Secondary objectives of the trial
    We will assess a number of clinical and immunological effects of treatment at several time points during the study. Again, the main comparison will be after 12 months treatment and between active and placebo-treated participants. Furthermore, the healthy, atopic participants will serve as a control at 12 months. Assessment will include the following:

    1. Measurement of the size (cross-sectional area in cm2) of local skin swelling caused by injection of purified grass pollen allergen into the skin of the forearm.

    2. An average of hay fever symptoms and use of hay fever medications during the pollen season, as recorded by weekly diaries.

    3. The results of immunological tests on blood, nasal fluid, nasal brushing and biopsy samples, such as the levels of ‘protective’ antibodies in blood serum.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Atopic participants:

    1. Adults age 18 to 65 years.
    2. A clinical history of grass pollen-induced allergic rhinoconjunctivitis for at least 2 years with peak symptoms in mid-May to mid-July.
    3. A clinical history of moderate to severe rhino conjunctivitis symptoms with or without mild seasonal asthma interfering with usual daily activities or with sleep.
    4. A clinical history of rhino conjunctivitis with or without mild seasonal asthma that remains troublesome despite treatment with either antihistamines or nasal corticosteroids during the grass pollen season.
    5. Positive skin prick test response, defined as wheal diameter ≥ 3 mm, to timothy grass pollen.
    6. Positive specific IgE, defined as IgE immunoCAP ≥ 0.7 ISU, against timothy grass pollen.
    7. For women of childbearing age, a negative urine pregnancy test at the time of screening must be present and they should have expressed the willingness to use an effective form of contraception for the duration of involvement in the study.
    8. The ability to give informed consent and comply with study procedures.
    9. Nasal challenge with 5.000 BU/ml and consecutive Total nasal symptom score (TNSS) after 5 minutes ≥ 7/12.

    Healthy, non-atopic participants:

    1. Adults age 18 to 65 years.
    2. Negative skin prick test response to timothy grass pollen and panel of aeroallergens.
    3. Negative specific IgE, defined as IgE immunoCAP < 0.35 ISU, against timothy grass pollen.
    4. For women of childbearing age, a negative urine pregnancy test at the time of screening and willingness to use an effective form of contraception for the duration of involvement in the study.
    5. The ability to give informed consent and comply with study procedures.
    E.4Principal exclusion criteria
    Atopic participants:

    1. Previous grass pollen allergen immunotherapy.
    2. Prebronchodilator FEV1 < 70% of predicted value at screening (out of grass-pollen season).
    3. A clinical history of symptomatic allergic rhinitis and/or asthma caused by an allergen to which the participant is regularly and perennially exposed (e.g. cat dander).
    4. Perennial asthma requiring regular inhaled corticosteroids.
    5. Seasonal symptoms outside the grass-pollen season (e.g. March to April with sensitization to birch pollen giving a hint to symptomatic polyallergenic)
    6. History of emergency visit or hospital admission for asthma in the previous 12 months.
    7. History of chronic obstructive pulmonary disease.
    8. History of significant recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment.
    9. History of chronic sinusitis, defined as a sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, and ear pain, pressure, or fullness.
    10. At screening visit, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
    11. Current smokers or a history of ≥ 5 pack years.
    12. History of life-threatening anaphylaxis or angioedema.
    13. Ongoing systemic immunosuppressive treatment.
    14. The use of any investigational drug within 30 days of the screening visit.
    15. The presence of any medical condition that the investigator deems incompatible with participation in the study.
    16. History of fish allergy with positive skin test and/or positive specific IgE test to vertebrate/finned fish.

    Non-atopic participants:

    1. Previous grass pollen allergen immunotherapy.
    2. Prebronchodilator FEV1 < 70% of predicted value at screening (out of grass-pollen season).
    3. A clinical history of symptomatic allergic rhinitis and/or asthma caused by an allergen to which the participant is regularly and perennially exposed (e.g. cat dander).
    4. Perennial asthma requiring regular inhaled corticosteroids.
    5. Seasonal symptoms outside or during the grass-pollen season.
    6. History of emergency visit or hospital admission for asthma in the previous 12 months.
    7. History of chronic obstructive pulmonary disease.
    8. History of significant recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment.
    9. History of chronic sinusitis, defined as sinus symptoms lasting greater than 12 weeks that includes 2 or more major factors or 1 major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, ear pain, pressure, or fullness.
    10. At screening visit, current symptoms of, or treatment for, upper respiratory tract infection, acute sinusitis, acute otitis media, or other relevant infectious process; serous otitis media is not an exclusion criterion. Participants may be re-evaluated for eligibility after symptoms resolve.
    11. Current smokers or a history of ≥ 5 pack years.
    12. History of life-threatening anaphylaxis or angioedema.
    13. Ongoing systemic immunosuppressive treatment.
    14. The use of any investigational drug within 30 days of the screening visit.
    15. The presence of any medical condition that the investigator deems incompatible with participation in the study.
    E.5 End points
    E.5.1Primary end point(s)
    We will use a well-established Questionnaire (Total Nasal Symptom Score, TNSS) to record nasal symptoms during the first 60 minutes after nasal allergen challenge (purified grass pollen sprayed into the nose). Specifically, we will look at whether the response to the allergen challenge is different in participants receiving active treatment compared to those receiving dummy treatment (placebo), after 12 months of treatment.
    E.5.1.1Timepoint(s) of evaluation of this end point
    (please see above)
    E.5.2Secondary end point(s)
    1. Cross-sectional area in cm2 of EPR and LPR skin responses to intradermal grass pollen allergen injection at 12 months in active versus placebo treated participants.

    2. Mean combined symptom + medication scores over the course of the 2014 grass pollen season in active versus placebo-treated participants.

    3. Serum and nasal fluid grass pollen specific IgG4 level and inhibition of B cell IgE-facilitated allergen binding in active versus placebo-treated patients versus non-atopic controls at 12 months.

    4. Allergen-induced peripheral blood basophil activation in active versus placebo-treated participants versus non-atopic controls at 12 months.

    5. Proportion of allergen-specific phenotypic Treg cells in peripheral blood as measured by flow cytometry in active vs placebo-treated patients versus non-atopic controls at 12 months.

    Exploratory endpoints will include, in active versus placebo-treated patients versus non-atopic controls at 12 months: the frequency of putative Breg cells in peripheral blood; the molecular binding profiles of IgE and IgG4 antibodies; T and B cell receptor sequencing; frequency of putative type 2 innate lymphoid cells (ILC2s).
    E.5.2.1Timepoint(s) of evaluation of this end point
    (please see above)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Explore mechanisms of immunotherapy
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last visit of last participant.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days30
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days30
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state64
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Participants in the placebo arm will be offered 24 months of active treatment. This will be distinct from the previous study.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-10-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-10-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-03-01
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