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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42567   clinical trials with a EudraCT protocol, of which   7008   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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:
    Clinical efficacy and safety of J022X ST in the prevention of Recurrent Upper-Respiratory Tract Infections (RURTI) in children with a high risk of recurrence

    Summary
    EudraCT number
    2013-001760-31
    Trial protocol
    IT   LT   PL   RO  
    Global end of trial date
    17 Oct 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    02 May 2017
    First version publication date
    02 May 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    J0022XST302
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pierre Fabre Medicament
    Sponsor organisation address
    45 place Abel Gance, Boulogne, France, 92100
    Public contact
    Elisabeth Carriere Roussel, IRPF 3 avenue Hubert Curien 31100 Toulouse, +33 5 34 50 63 48,
    Scientific contact
    Elisabeth Carriere Roussel, IRPF 3 avenue Hubert Curien 31100 Toulouse, +33 5 34 50 63 48,
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Apr 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Oct 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the clinical efficacy of J022X ST in preventing RURTI in young children at risk.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles stated in the Declaration of Helsinki (1964 and its subsequent amendments). This study was conducted in agreement with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines and with applicable national regulations in biomedical research (except in one Romanian centre: see "Recruitment details" caption). The first study protocol version in use , all its amendments, and the patient information sheets, were reviewed by the appropriate independent ethics committees (IECs), including local IECs. This study was placebo-controlled (see rationale in "Evidence for comparator"). In Year 2 of this study, the treatment was proposed only to children having proven recurrent upper respiratory tract infection (RURTI) and for whom it could be beneficial The placebo group received the same medical care as the J00022X group, according to that which would have been provided if they had not participated in this study. If patients showed any early signs of safety concerns or aggravation of symptoms during the study, they were eligible to receive alternative active therapy at any time.
    Background therapy
    There was no systematic concomitant administration of any other product than investigational products.
    Evidence for comparator
    This study was placebo-controlled as there is still a medical need for alternative treatments As no other product had formally proven its efficacy in prevention of URTIs and could be considered as a reference product, efficacy was assessed vs. placebo. The use of a placebo control was critical to the study to allow discrimination between patient outcomes caused by J0022XST and outcomes caused by other factors (e.g. the observer or patient expectations, the natural acquisition of immunity, the conditions of study participation).
    Actual start date of recruitment
    02 Sep 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
    Poland: 197
    Country: Number of subjects enrolled
    Romania: 365
    Country: Number of subjects enrolled
    Italy: 114
    Country: Number of subjects enrolled
    Lithuania: 168
    Country: Number of subjects enrolled
    Russian Federation: 150
    Worldwide total number of subjects
    994
    EEA total number of subjects
    844
    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)
    994
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    This phase III study was conducted in two parts: year 1 was an observational phase to select children with RURTI i.e. at least 6 episodes of medically confirmed URTI. year 2: . If eligible, patients were randomised to one of the 2 treatment groups (J022X ST or placebo)

    Pre-assignment
    Screening details
    53 centres located in 5 countries (France, Hungary, Romania, Latvia, Russian Federation) were initiated, 50 centers had at least one patient included and 30 recruited patients. . 1003 Children aged 3-4 year, known for RURTI were screened, 994 were included in year 1 (observational phase), 254 were randomised and analysed

    Pre-assignment period milestones
    Number of subjects started
    994
    Number of subjects completed
    254

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    non premature withdrawal not conitnuing: 467
    Reason: Number of subjects
    premature withdrawal for other reason: 272
    Reason: Number of subjects
    premature withdrawal for safety: 1
    Period 1
    Period 1 title
    Year 1
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer
    Blinding implementation details
    Double-blinding was ensured by identical packaging, labelling and administration of the investigational treatments

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    J0022 X ST
    Arm description
    experimental
    Arm type
    Experimental

    Investigational medicinal product name
    J0022X ST
    Investigational medicinal product code
    Other name
    Ribomunyl/immucytal/Biomunil
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    • Active substancea: 0.525 mgb, given as ribosomal RNA content. Ribosomal fractions (10 parts) including: - Klebsiella pneumoniae (3.5 parts) - Streptococcus pneumoniae (3 parts) - Streptococcus pyogenes group A (3 parts) - Haemophilus influenzae (0.5 parts) And membrane fraction (15 parts) including: - Klebsiella pneumoniae. In the first month of treatment, the patient took one sachet in the morning on an empty stomach for 4 consecutive days per week, for 3 consecutive weeks. From the second month of treatment, the patient took one sachet in the morning on an empty stomach for 4 consecutive days per month, at monthly intervals, for 5 consecutive months.

    Arm title
    Placebo
    Arm description
    -
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Granules in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    In the first month of treatment, the patient took one sachet in the morning on an empty stomach for 4 consecutive days per week, for 3 consecutive weeks. From the second month of treatment, the patient took one sachet in the morning on an empty stomach for 4 consecutive days per month, at monthly intervals, for 5 consecutive months.

    Number of subjects in period 1 [1]
    J0022 X ST Placebo
    Started
    122
    132
    Completed
    122
    132
    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: A total of 740 out of the 994 included patients (73.8%) in year 1 were not randomised in Year 2 due to non premature withdrawal not continuing (467 patients [46.6%]), premature withdrawal for other reason (272 patients [27.1%]) and premature withdrawal for safety reason (one patient [0.1%]). For most patients (609 patients [60.7%]), the categorised reason for non randomisation was because of insufficient URTI épisodes.
    Period 2
    Period 2 title
    year 2
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    J0022 X ST
    Arm description
    experimental
    Arm type
    Experimental

    Investigational medicinal product name
    J0022X ST
    Investigational medicinal product code
    Other name
    Ribomunyl/immucytal/Biomunil
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    • Active substancea: 0.525 mgb, given as ribosomal RNA content. Ribosomal fractions (10 parts) including: - Klebsiella pneumoniae (3.5 parts) - Streptococcus pneumoniae (3 parts) - Streptococcus pyogenes group A (3 parts) - Haemophilus influenzae (0.5 parts) And membrane fraction (15 parts) including: - Klebsiella pneumoniae. In the first month of treatment, the patient took one sachet in the morning on an empty stomach for 4 consecutive days per week, for 3 consecutive weeks. From the second month of treatment, the patient took one sachet in the morning on an empty stomach for 4 consecutive days per month, at monthly intervals, for 5 consecutive months.

    Arm title
    Placebo
    Arm description
    Control arm
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Granules in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    In the first month of treatment, the patient took one sachet in the morning on an empty stomach for 4 consecutive days per week, for 3 consecutive weeks. From the second month of treatment, the patient took one sachet in the morning on an empty stomach for 4 consecutive days per month, at monthly intervals, for 5 consecutive months.

    Number of subjects in period 2
    J0022 X ST Placebo
    Started
    122
    132
    Completed
    122
    132

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    J0022 X ST
    Reporting group description
    experimental

    Reporting group title
    Placebo
    Reporting group description
    -

    Reporting group values
    J0022 X ST Placebo Total
    Number of subjects
    122 132 254
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Age at year 1
    Units: years
        arithmetic mean (standard deviation)
    3.2 ± 0.4 3.3 ± 0.5 -
    Gender categorical
    Units: Subjects
        Female
    61 65 126
        Male
    61 67 128
    Subject analysis sets

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Full Analysis Set (FAS), composed of all patients randomised in Year 2, having received at least one dose of the study treatment. This set was used to perform analyses for efficacy and safety.

    Subject analysis sets values
    Full analysis set
    Number of subjects
    254
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Age at year 1
    Units: years
        arithmetic mean (standard deviation)
    3.2 ± 0.4
    Gender categorical
    Units: Subjects
        Female
        Male

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    J0022 X ST
    Reporting group description
    experimental

    Reporting group title
    Placebo
    Reporting group description
    -
    Reporting group title
    J0022 X ST
    Reporting group description
    experimental

    Reporting group title
    Placebo
    Reporting group description
    Control arm

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Full Analysis Set (FAS), composed of all patients randomised in Year 2, having received at least one dose of the study treatment. This set was used to perform analyses for efficacy and safety.

    Primary: Difference in the number of URTI between J0022XST and placebo at year 2

    Close Top of page
    End point title
    Difference in the number of URTI between J0022XST and placebo at year 2
    End point description
    Treatment effect on the number of URTI episodes medically assessed by the Investigator over the 12 months of Year 2 was tested using an analysis of covariance (ANCOVA) model. This model included age at randomisation in Year 2, sex and year of randomisation as covariates, and country as stratum factor. The primary analysis was performed on the FAS and repeated on the PP Set as a supportive analysis.
    End point type
    Primary
    End point timeframe
    The main statistical objective was to show a difference in the number of URTIs in Year 2 between J022X ST and placebo on the FAS.
    End point values
    J0022 X ST Placebo
    Number of subjects analysed
    122
    132
    Units: ajusted mean difference
    122
    132
    Statistical analysis title
    Primary analysis
    Statistical analysis description
    Treatment effect on the number of URTI episodes medically assessed by the Investigator over the 12 months of Year 2 was tested using an analysis of covariance (ANCOVA) model. This model included age at randomisation in Year 2, sex and year of randomisation as covariates, and country as stratum factor. The primary analysis was performed on the FAS and repeated on the PP Set as a supportive analysis.
    Comparison groups
    J0022 X ST v Placebo
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.21
    Method
    ANCOVA
    Parameter type
    Median difference (net)
    Point estimate
    -0.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    -0.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Notes
    [1] - The main statistical objective was to show a difference in the number of URTIs in Year 2 between J022X ST and placebo on the FAS with the following null hypothesis H0a: there was no difference between treatments in the number of URTIs in Year 2 vs. H1a: there was a difference between treatments.

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From randomisation to End of Study Visit (expected to be V10/D50 or V9/D43 the End of Treatment Visit if the patient did not enter the follow-up)
    Adverse event reporting additional description
    AEs and AEs other than URTIs, reported in Year 2 : i.e. defined as any AEs started after the Randomisation visit of Year 2 or ongoing at the Randomisation visit of Year 2
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    J0022 X ST
    Reporting group description
    experimental

    Reporting group title
    Placebo
    Reporting group description
    -

    Serious adverse events
    J0022 X ST Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 122 (0.00%)
    2 / 132 (1.52%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Gastrointestinal disorders
    appendicitis
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 132 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 132 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acetonaemia
    Additional description: the same patient presented constipation, acetonaemia and gastritis leading to hospitalisation beacause of abdominal pain
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 132 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 122 (0.00%)
    1 / 132 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2.5%
    Non-serious adverse events
    J0022 X ST Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    93 / 122 (76.23%)
    97 / 132 (73.48%)
    Gastrointestinal disorders
    Enterocolitis
         subjects affected / exposed
    7 / 122 (5.74%)
    6 / 132 (4.55%)
         occurrences all number
    7
    7
    Diarrhoea
         subjects affected / exposed
    1 / 122 (0.82%)
    3 / 132 (2.27%)
         occurrences all number
    1
    3
    Infections and infestations
    Tonsilitis
         subjects affected / exposed
    45 / 122 (36.89%)
    45 / 132 (34.09%)
         occurrences all number
    77
    63
    Nasopharyngitis
         subjects affected / exposed
    35 / 122 (28.69%)
    36 / 132 (27.27%)
         occurrences all number
    52
    64
    Laryngitis
         subjects affected / exposed
    35 / 122 (28.69%)
    36 / 132 (27.27%)
         occurrences all number
    52
    64
    Otitis media acute
         subjects affected / exposed
    18 / 122 (14.75%)
    17 / 132 (12.88%)
         occurrences all number
    23
    23
    Pharyngitis
         subjects affected / exposed
    14 / 122 (11.48%)
    13 / 132 (9.85%)
         occurrences all number
    19
    17
    Varicela
         subjects affected / exposed
    10 / 122 (8.20%)
    5 / 132 (3.79%)
         occurrences all number
    10
    5
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 122 (6.56%)
    13 / 132 (9.85%)
         occurrences all number
    25
    27
    Sinusitis
         subjects affected / exposed
    6 / 122 (4.92%)
    13 / 132 (9.85%)
         occurrences all number
    8
    16
    Bronchitis
         subjects affected / exposed
    5 / 122 (4.10%)
    8 / 132 (6.06%)
         occurrences all number
    8
    9
    Rhinitis
         subjects affected / exposed
    5 / 122 (4.10%)
    7 / 132 (5.30%)
         occurrences all number
    6
    8
    Otitis media
         subjects affected / exposed
    4 / 122 (3.28%)
    1 / 132 (0.76%)
         occurrences all number
    5
    1
    Conjuncivitis
         subjects affected / exposed
    3 / 122 (2.46%)
    4 / 132 (3.03%)
         occurrences all number
    4
    4
    Pneumonia
         subjects affected / exposed
    3 / 122 (2.46%)
    2 / 132 (1.52%)
         occurrences all number
    3
    2

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Mar 2014
    Addition of the CROs involved in the study Update of the planned study period according to the approval from AIFA Precision on inclusion and non-inclusion criteria (e.g. other diseases and relating to treatments) Precision on premature withdrawal visits of Year 1 and Year 2 Correction of flow-chart Addition of the Interactive Web Response System (IWRS) procedure Addition of information due to the modification of the safety document reference (Italian Summary of Product Characteristics→Safety section of the Investigator’s Brochure as requested by Russian Authorities Addition of requests made by the Russian Ministry of Health Change of Clinical Study Manager and modification of the Corporate Safety Officer’s contact details Removal of information on the Head of Therapeutic Area
    17 Jul 2014
    Addition of paracetamol and NSAIDs for URTI as authorised treatments Clarification that ibuprofen had to be prescribed at more than 30 mg/kg/day in the definition of a severe URTI Clarification that anti-histamines could be prescribed during the study Addition of information on test product quantity Removal of the IWRS and update of the treatment number allocation procedure Replacement of the Medical Study Manager by the Clinical Program Director

    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
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA