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   44311   clinical trials with a EudraCT protocol, of which   7356   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

    Print Download

    Summary
    EudraCT Number:2015-001763-39
    Sponsor's Protocol Code Number:MU1441
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-06-09
    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 ConcernedGermany - BfArM
    A.2EudraCT number2015-001763-39
    A.3Full title of the trial
    E. coli Nissle 1917 - Suspension for infection prophylaxis
    E. coli Nissle 1917 - Suspension zur Infektionsprophylaxe
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    E. coli Nissle 1917 - Suspension for infection prophylaxis
    E. coli Nissle 1917-Suspension zur Infektionsprophylaxe
    A.3.2Name or abbreviated title of the trial where available
    RONi-STUDY
    RONi-STUDIE
    A.4.1Sponsor's protocol code numberMU1441
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02802059
    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 SponsorArdeypharm GmbH
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportArdeypharm GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Mutaflor® Suspension
    D.2.1.1.2Name of the Marketing Authorisation holderArdeypharm GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical form Oral suspension
    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.3.9.3Other descriptive nameE. coli Nissle 1917, EcN
    D.3.10 Strength
    D.3.10.1Concentration unit CFU/ml colony forming unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1E08
    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) 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 Yes
    D.3.11.13.1Other medicinal product typeprobiotic
    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 suspension
    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
    Following viral and bacterial infections:

    - Acute upper respiratory tract infections (i.e. rhinopharyngitis, laryngitis, angina tonsillitis, tracheitis)
    - Acute lower respiratory tract infections (i.e. bronchitis, bronchiolitis, bronchopneumonia, pneumonia)
    - Otitis media
    - Gastroenteritis
    - Urinary tract infections.

    Folgende Infektionen viraler und bakterieller Ursprungs:

    - Akute Infektionen der oberen Atemwege (z.B. Rhinopharyngitis, Laryngitis, Angina tonsillaris, Tracheitis),
    - Akute Infektionen der unteren Atemwege (Bronchitis, Bronchiolitis, Bronchiopneumonie, Pneumonie),
    - Otitis media,
    - Gastroenteritis,
    - Harnwegsinfektionen.
    E.1.1.1Medical condition in easily understood language
    Viral and bacterial infecrions.
    Virale und bakterielle Infektionen.
    E.1.1.2Therapeutic area Not possible to specify
    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 main objective is to show that the administration of E.coli strain Nissle 1917 results in the reduction of the number of both bacterial and viral infections during the first 24 months of infant’s life.
    Das Hauptziel ist es zu zeigen, dass die Verabreichung von E.coli strain Nissle 1917 zu einer Reduktion viraler und bakterieller Infektionen innerhalb der ersten 2 Lebensjahre führt.
    E.2.2Secondary objectives of the trial
    The secondary objectives are to show that the administration of E.coli strain Nissle 1917 reduces the severity of the course of the infections considered as primary variables and to reveal that the trial medication is generally well tolerated.
    Die Nebenziele sind es zu zeigen, dass die Verabreichung von E. coli Nissle 1917 zu einer Verlaufsmilderung der Infektionen, die als Hauptzielvariable erfasst werden, führt und generell gut verträglich ist.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Additional non-clinical explorative evaluation:
    The aim of the additional evaluation is to investigate whether the early intestinal colonization with E.coli strain Nissle 1917 affects the establishment of the intestinal microbiota.
    Zusätzliche nicht-klinische explorative Untersuchung:
    Das Ziel der zusätzlichen Untersuchung ist es zu evaluieren, ob die frühe Besiedlung des Darms mit E. coli Nissle 1917 den Aufbau der intestinalen Mikrobiota beeinflusst.
    E.3Principal inclusion criteria
    - Signed informed consent form by the parents
    - Age at first intake of trial medication: max. 120 hours after birth
    - Functionally mature infant
    - Gestational age more than 35th week of development
    - Intention of the mother to breast feed the participant
    - Readiness of the mother to administer no probiotics additionally to the trial medication to the participant during entire course of the study.
    - Unterschriebene Einverständniserklärung,
    - Alter bei Ersteinnahme der Prüfmedikation: max. 120 Stunden nach der Geburt,
    - Anamnestisch gesundes Kind,
    - Vollendung der 35. Schwangerschaftswoche,
    - Vorhaben der Mutter, das Kind mit Muttermilch zu ernähren,
    - Die Bereitschaft der Mutter, auf die Gabe von anderen Probiotika für die Dauer der Studienteilnahme zu verzichten.
    E.4Principal exclusion criteria
    - Non-fulfilment of the at least one inclusion criteria
    - Lack of propensity/ compliance of mother
    - 5 min APGAR SCORE less than 5
    - 10 min APGAR SCORE less than 8
    - pH of umbilical cord blood less than 7*
    * Determination not obligatory, if APGAR SCORES do not indicate that the child may have suffered from a perinatal asphyxia.
    - Any perinatal infection required antibiotic treatment
    - Birth weight less than 2000 g
    - TORCH-infection of the mother
    - HIV-infection of the mother
    - Any severe medical condition of mother or newborn which in the opinion of the investigator may have a critical impact on the conduct of the study.
    - Nicht-Erfüllen der Einschlusskriterien,
    - Mangelnde Kooperationsbereitschaft der Mutter,
    - 5 min APGAR SCORE ≤5,
    - 10 min APGAR SCORE ≤8,
    - Der pH-Wert vom Nabelschnurblut <7*,
    * Bestimmung nicht notwendig, wenn die APGAR SCORES keinen Hinweis auf eine perinatale Asphyxie geben.
    - Perinatal aufgetretene Infektionen, die zur Antibiotika-Behandlung führen,
    - Die Neugeborenen mit einem Geburtsgewicht unter 2000 g,
    - TORCH-Infektion der Mutter,
    - HIV-Infektion der Mutter,
    - sonstige anamnestische Konditionen der Mutter oder des Neugeborenen, deren klinische Auswirkungen aus der Sicht des Prüfarztes die Durchführung der Studie verhindert.
    E.5 End points
    E.5.1Primary end point(s)
    The total number of infections (bacterial and viral) observed for each participant during its individual study participation standardised per month during the first 24 months of life. An infection is an episode of illness caused by:
    • Acute upper respiratory tract infections (i.e. rhinitis*, pharyngitis, laryngitis, tracheitis angina tonsillitis, and combinations of these)
    • Acute lower respiratory tract infections (i.e. bronchitis, bronchiolitis, bronchopneumonia, pneumonia and combinations of these)
    • Otitis media
    • Gastroenteritis
    • Urinary tract infections
    The duration of an episode of illness is defined as the time from the appearance of the first symptom of a study relevant infection to the disappearance of the last symptom of a study relevant infection. Study relevant infections that occur concurrently, or one after another, within a period of 7 days are only counted separately, if they belong to different groups of illness.
    * All rhinitides that occur in the first year of a child’s life are considered for the count of the primary efficacy variable. Rhinitides that occur in the second year of a child’s life are only included if they were accompanied by fever.
    Die Anzahl von Infektionen innerhalb der ersten 24 Lebensmonate, normiert für die individuelle Teilnahmedauer des Probanden. Eine Infektion ist eine Krankheitsepisode, die verursacht wird durch:
    • Akute Infektionen der oberen Atemwege (Rhinitis*, Pharyngitis, Laryngitis, Tracheitis, Angina tonsillitis und Kombinationen dieser),
    • Akute Infektionen der unteren Atemwege (Bronchitis, Bronchiolitis, Bronchopneumonia, Pneumonia und Kombinationen dieser),
    • Otitis media,
    • Gastroenteritis,
    • Harnwegsinfektionen
    Die Dauer einer Krankheitsepisode ist definiert als die Zeit vom Auftreten des ersten Symptoms einer studienrelevanten Infektion bis zum Verschwinden des letzten Symptoms einer studienrelevanten Infektion. Studienrelevante Infektionen, die gleichzeitig oder nacheinander innerhalb eines Zeitraums von 7 Tagen auftreten, werden nur dann separat gezählt, wenn sie zu verschiedenen Krankheitsgruppen gehören.
    *Alle Rhinitiden, die im ersten Lebensjahr eines Kindes auftreten, werden für die Zählung des primären Endpunktes berücksichtigt. Rhinitiden, die im zweiten Lebensjahr eines Kindes auftreten, werden nur berücksichtigt, wenn sie von Fieber begleitet wurden.
    E.5.1.1Timepoint(s) of evaluation of this end point
    After observation period of 24 months.
    Nach einer Beobachtungszeit von 24 Monaten.
    E.5.2Secondary end point(s)
    The reduction of the severity of the course of the infections considered as primary variables:
    - Duration of the infection (number of days with at least one symptom)
    - Number of hospital admissions caused by infections
    - Mean number of in-hospital spent days
    - Number of antibiotic treatments
    - Adverse events
    - Tolerance to trial medication
    Die Verlaufsmilderung der Infektionen, die als Hauptzielvariable erfasst werden:
    - Krankheitsdauer, bezogen auf das Vorhandensein von mindestens eines Symptoms,
    - Anzahl der infektionsbedingten Hospitalisierungen,
    - Dauer der Hospitalisierungen aufgrund der als Hauptzielparameter erfassten Infektionen (Tage, pro Hospitalisierungsereignis),
    - Anzahl von Antibiotika-Behandlungen,
    - Unerwünschte Ereignisse,
    - Verträglichkeit der Studienmedikation.
    E.5.2.1Timepoint(s) of evaluation of this end point
    After observation period of 24 months.
    Nach einer Beobachtungszeit von 24 Monaten.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety No
    E.6.5Efficacy No
    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) No
    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 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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    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: 558
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Yes
    F.1.1.3Newborns (0-27 days) Yes
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Age at inclusion: max. 120 hours of life
    maximales Alter bei Einschluss: 120 h nach der Geburt
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state458
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 558
    F.4.2.2In the whole clinical trial 558
    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)
    Since the participants are healthy subjects the treatment after the participation in the trial is not indicated. Two years after the end of the participation each subject will be examined for their normal physical and cognitive development.
    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 Decision2015-07-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-10-12
    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 © 1995-2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA