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    Summary
    EudraCT Number:2017-004539-36
    Sponsor's Protocol Code Number:16NC06
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2020-10-14
    Trial 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 number2017-004539-36
    A.3Full title of the trial
    Study of Montelukast In Children with Sickle Cell Disease (SMILES)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of Montelukast In Children with Sickle Cell Disease
    A.3.2Name or abbreviated title of the trial where available
    SMILES
    A.4.1Sponsor's protocol code number16NC06
    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 SponsorGreat Ormond Street Hospital for Children NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGreat Ormond Street Hospital for Children NHS Foundation Trust
    B.5.2Functional name of contact pointIlyas Ali
    B.5.3 Address:
    B.5.3.1Street AddressJoint Research and Development Office, 30 Guilford St
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeWC1N 1EH
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44 (0)20 7905 2863
    B.5.5Fax number+44 (0)20 7905 2201
    B.5.6E-maililyas.ali@gosh.nhs.net
    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 Montelukast
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Limited Sage House, 319 Pinner Road, North Harrow, Middlesex, United Kingdom, HA1
    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 nameMontelukast
    D.3.2Product code N/A
    D.3.4Pharmaceutical form Chewable tablet
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMontelukast Sodium
    D.3.9.1CAS number 151767-02-1
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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) No
    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 placeboChewable tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Sleep-disordered breathing
    E.1.1.1Medical condition in easily understood language
    Obstructive Sleep Apnoea
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Psychological processes [F02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10078294
    E.1.2Term Obstructive sleep apnoea hypopnoea syndrome
    E.1.2System Organ Class 100000004855
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10040977
    E.1.2Term Sleep apnoea
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the effect of Montelukast on neurocognition, specifically processing speed measured as Cancellation (Wechsler scales) and NIH toolbox processing speed.
    E.2.2Secondary objectives of the trial
    • To assess the effect of Montelukast on
    -adenoid:nasopharynx size
    -brain MRI
    -overnight oximetry,
    -symptoms of sleep-disordered breathing, e.g. snoring
    -sleep duration and
    -Pain
    • To assess side-effects of Montelukast
    • To assess feasibility of MRI in children aged 3-<8 years.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Aged between 3 and <8 years
    • Informed consent with assent in accordance with institutional policies and European guidelines; ICF must be signed by patients/guardian
    • HbSS or HbSβ0 thalassaemia diagnosed by standard techniques (HPLC, IEF, MS or AlkE)
    • History of Sleep-Disordered Breathing, (i.e. parent-reported any degree of snoring (CHSQ questionnaire) and/or any abnormality on overnight oximetry compared with published data in children of the same age (e.g. nadir SO2<93%; mean SO2<96%))
    • In steady state i.e. haemoglobin not decreased by >10% in previous year, no painful crisis requiring opioids for at least 1 month and at least 1 month after any hospital admission
    • Likely to comply with treatment for 3 months as determined by the local paediatrician or hematologist
    • Able to speak and understand English
    E.4Principal exclusion criteria
    • Other developmental or psychiatric disorders including craniofacial abnormalities, neuromuscular disorder and other chronic conditions.
    • Patient already on montelukast
    • Patient has had side effects on or an adverse reaction to montelukast in the past
    • Presence or history of another hemoglobinopathy or blood dyscrasia
    • Concomitant treatment with any other leukotriene antagonist within a window period of enrolment
    • Participation on other SCD/Montelukast trials
    E.5 End points
    E.5.1Primary end point(s)
    The trial is powered to look at 2 primary outcomes
    1. Cancellation (paper-and-pencil test of processing speed and attention from the Wechsler scales)
    2. Processing speed on the NIH toolbox
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline before treatment and after 12 weeks of treatment
    E.5.2Secondary end point(s)
    o NIH toolbox executive function
    o Duration of Sleep from Children’s Sleep Habit questionnaire (CSHQ)
    o Symptoms of Sleep Disordered Breathing from Pediatric Sleep questionnaire (PSQ)
    o Pain burden from sickle module of PEDSQL
    o AEs & drug side-effects

    * Additional secondary endpoints in patients willing to undergo optional additional tests (MRI without sedation (awake/asleep); overnight oximetry):

    o Self-rated pain diaries via trial smartphone app
    o Core MRI endpoints: Multiparametric maps (MPM) for adenoidal and brain size, Volumetrics(T1 MRI), White matter integrity and structural connectivity (DWI),

    * Additional MRI endpoints if tolerated:

    Perfusion (ASL), Functional Connectivity (rsFMRI), Multiparametric maps (MPM), Oxygen-extraction fraction (TRUST)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Baseline before treatment and after 12 weeks of treatment
    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 No
    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) Yes
    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 Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days31
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days31
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 200
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 200
    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) No
    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 No
    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 state200
    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)
    Patients will discontinue treatment at the end of the study. If the study shows that montelukast is of benefit and is cost effective it may be offered to patients in the future.

    Montelukast can be prescribed by the local Paediatrician.
    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 Decision2020-05-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-01-15
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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