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    The EU Clinical Trials Register currently displays   43884   clinical trials with a EudraCT protocol, of which   7296   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).

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    Summary
    EudraCT Number:2016-001120-54
    Sponsor's Protocol Code Number:SQ167015
    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:2016-07-01
    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 number2016-001120-54
    A.3Full title of the trial
    Does the DPP4 Inhibitor (Sitagliptin) Increase Endometrial Mesenchymal Stem Cells in Women with Recurrent Miscarriage?
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    SIMPLANT
    A.3.2Name or abbreviated title of the trial where available
    SIMPLANT
    A.4.1Sponsor's protocol code numberSQ167015
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity Hospitals Coventry and Warwickshire NHS 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 supportTommy's
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Hospitals Coventry and Warwickshire NHS Trust
    B.5.2Functional name of contact pointDr Shreeya Tewary
    B.5.3 Address:
    B.5.3.1Street AddressUniversity Hospital, Clifford Bridge Road, Walsgrave
    B.5.3.2Town/ cityCoventry
    B.5.3.3Post codeCV2 2DX
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02476967528
    B.5.6E-mailshreeya.tewary@uhcw.nhs.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 Januvia
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme Ltd
    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 nameSitagliptin
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    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 INNSitagliptin phosphate monohydrate
    D.3.9.1CAS number 654671-78-0
    D.3.9.3Other descriptive nameJanuvia
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100mg
    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 placeboCapsule
    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
    Recurrent miscarriage
    E.1.1.1Medical condition in easily understood language
    Those patients who have had three or more miscarriages
    E.1.1.2Therapeutic area Body processes [G] - Reproductive physiologi cal processes [G08]
    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
    The primary objective is to determine the effect of Sitagliptin on endometrial mesenchymal stem cell count. This will be assessed by the number of colonies per thousand endometrial stromal cells after 3 months of Sitagliptin (100mg) vs. 3 months of placebo, determined by a clonogenic assay.
    E.2.2Secondary objectives of the trial
    The secondary objectives are to
    1. To determine the effect of Sitagliptin on the expression of DPP4 at the endometrium. This will be assessed by looking at the change in the expression of DPP4 in the endometrium determined by immunohistochemistry.

    2. To understand the effect of Sitagliptin administration on other implantation related genes. This will be assessed by RNA sequencing of endometrial mesenchymal stem cells and methylation status of implantation related genes after 3 months of Sitagliptin (100mg) vs. 3 months of placebo

    4. To determine how well the IMP dosing schedule is tolerated by participants. This will be assessed by qualitative analysis of adverse events/serious adverse events reported in each treatment group (Sitagliptin vs. placebo). This analysis will include information collected onto the trial database at the 4 weekly follow up and also from a questionnaire given to them at the end of the trial.

    5. To determine the acceptability of the protocol to study
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Provision of informed written consent
    - History of recurrent miscarriage - 3 or more miscarriages, defined as three or more spontaneous pregnancy losses prior to 24 weeks gestation
    - Age 18-42 years at consent
    - Any BMI – no dose adjustment needed for BMI. BMI has no clinically meaningful effect on the pharmacokinetics of Sitagliptin.
    - Willing and able to give consent for the study and endometrial biopsy.
    - Ability to fully understand the requirements of the protocol
    - Adequate renal function , defined as Urea 2.5 – 7.8mmol/L, Creatinine 50 -90umol/L, potassium 3.5 – 5.3mmol/L, Sodium 133 -146mmol/L
    - Adequate hepatic function, defined as total protein 60 – 80g/L, Albumin 35-50g/L, Bilirubin 4-20umol/L, Alkaline Phosphatase (ALP) 35-105U/L, Alanine Transferase (ALT) 5-38 U/L
    - Negative pregnancy test on the day of randomisation
    E.4Principal exclusion criteria
    - Under 18 years of age – the safety and effectiveness of Sitagliptin in paediatric patients under 18 has not yet been established.
    - Type I Diabetes – Sitagliptin should not be used in type 1 diabetes
    - Type II Diabetes – based on medical history
    - Pregnancy: tested at multiple points in trial – see schedule of events
    - Breast feeding – Caution is advised when prescribing Sitagliptin to breastfeeding mothers as it is not known if it is secreted in breast milk.
    - Known hypersensitivity to Sitagliptin
    - Not taking any medications with potential to react with the interventional product including Digoxin –plasma monitoring is needed if Sitagliptin used concomitantly in those at risk of digoxin toxicity, and Enalapril – Sitagliptin appears to alter the hypotensive effects of enalapril.
    - Previous diagnosis of pancreatitis
    - Renal impairment with eGFR<50 mL/min
    - Liver impairment, defined as any value out of normal range (total protein 60 – 80g/L, Albumin 35-50g/L, Bilirubin 4-20umol/L, Alkaline Phosphatase (ALP) 35-105U/L, Alanine Transferase (ALT) 5-38 U/L)
    - Inclusion in another intervention trial
    - Unwilling to use effective contraception for the duration of the trial (from consent)
    - Allergy/sensitivity to excipients of the IMP/placebo
    E.5 End points
    E.5.1Primary end point(s)
    The number of colonies per thousand endometrial stromal cells after 3 months of 3 months of Sitagliptin (100mg) vs. 3 months of placebo, determined by a clonogenic assay.
    A standard operating procedure has been developed which describes in detail how the clonogenic assay is carried out.
    E.5.1.1Timepoint(s) of evaluation of this end point
    We will analyse endometrial biopsies as they are taken. The clonogenic assay takes a total of 12 days to complete.
    The last clonogenic assay from the last patient will be taken three months after randomisation.
    E.5.2Secondary end point(s)
    1. To determine the effect of Sitagliptin on the expression of DPP4 at the endometrium
    We will measure the change in the expression of DPP4 in endometrial after 3 months of Sitagliptin (100mg) vs. 3 months of placebo determined by immunohistochemistry

    2. To understand the effect of Sitagliptin administration on other implantation related genes
    We will do RNA sequencing of endometrial mesenchymal stem cells and methylation status of implantation related genes after 3 months of Sitagliptin (100mg) vs. 3 months of placebo

    3. To determine how well the IMP dosing schedule is tolerated by participants
    We will do a qualitative analysis of adverse events/serious adverse events reported in each treatment group (Sitagliptin vs. placebo)

    4. To determine the acceptability of the protocol to study participants
    We will do a qualitative analysis of process evaluation questionnaire in participants receiving IMP vs placebo.

    5. Comparison of pregnancy rates and outcomes in participants receiving IMP vs. placebo
    E.5.2.1Timepoint(s) of evaluation of this end point
    Immunohistohemistry, RNA sequencing ad methylation status will be done as the biopsies are taken,

    Qualitative analyses of how well the IMP dosing schedule was tolerated and the acceptability of the study will be performed as soon as possible after the participant has their second endometrial biopsy.

    Pregnancy rates will be followed up for a total of 9 months after 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) 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 Yes
    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 years1
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days1
    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: 34
    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 No
    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 state34
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 34
    F.4.2.2In the whole clinical trial 34
    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)
    This is a pilot study and so no treatment will be available for participants after completion of the study.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation N/A
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-07-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-06-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-02-12
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