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   43865   clinical trials with a EudraCT protocol, of which   7286   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

    Download PDF

    Clinical Trial Results:
    A phase II randomised, double blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of CT327 topical ointment (0.05% and 0.5% w/w) compared to vehicle, in subjects with mild or moderate atopic dermatitis and at least moderate pruritus

    Summary
    EudraCT number
    		 2012-005389-36
    Trial protocol
    		 GB  
    Global end of trial date
    30 Apr 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Jul 2019
    First version publication date
    14 Jul 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CT327-2005
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01808157
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Sienna Biopharmaceuticals SA
    Sponsor organisation address
    14 Rue Edward Steichen, Luxembourg, Luxembourg, L-2540
    Public contact
    Head of Clinical Operations, Sienna Biopharmaceuticals SA, 001 818-629-2256, ClinicalTrials@siennabio.com
    Scientific contact
    Head of Clinical Operations, Sienna Biopharmaceuticals SA, 001 818-629-2256, ClinicalTrials@siennabio.com
    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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Aug 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Apr 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Apr 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine whether CT327 is effective in reducing pruritus (itch) in subjects with atopic dermatitis, using a pruritus visual analogue scale (VAS), and to assess the efficacy of CT327 on atopic dermatitis using the Investigator Global Assessment (IGA)
    Protection of trial subjects
    Written informed consent was obtained prior to the subject entering the study and prior to initiation of any protocol-specified procedures. The investigator, or designee, explained the nature, purpose, and risks of the study to each subject and/or the subject’s parent or legal guardian. Subjects aged ≥16 years were provided with the adult information sheet and asked to sign the adult consent form. Subjects aged 12-15 years were given an age-appropriate information sheet and asked to give assent and the parent or legal guardian was asked to give consent. Each subject was informed that he/she could withdraw from the study at any time and for any reason and was given sufficient time to consider the implications of the study before deciding whether to participate. Safety assessments included adverse events (including local site reactions), changes in blood pressure, pulse, 12-lead electrocardiogram, laboratory safety tests, and physical examination.
    Background therapy
    		 No background therapy was used by all subjects.
    Evidence for comparator
    		 No active comparator was used; CT327 was compared with vehicle (ointment containing no CT327).
    Actual start date of recruitment
    05 Jul 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
    United Kingdom: 188
    Worldwide total number of subjects
    188
    EEA total number of subjects
    188
    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)
    0
    Adolescents (12-17 years)
    29
    Adults (18-64 years)
    147
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 299 subjects were screened to randomize 188 subjects. Recruitment was stratified with the intent that approximately 30% of recruited subjects would be adolescent (12-17 years).

    Pre-assignment
    Screening details
    		 At baseline, subjects had atopic dermatitis, as defined by the Hanifin and Rajka criteria, which involved a minimum of 5% and a maximum of 20% body surface area, an Investigator Global Assessment Score of 2 or 3 (mild or moderate) and pruritus visual analogue scale score of at least 40mm (at least moderate). Screening was within 21 days of Day 1.

    Period 1
    Period 1 title
    Treatment Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    The study was double-blind. Each study site was instructed on how to break the study blind using either the interactive web response system (IWRS) or telephone. Investigators were asked, where possible, to contact the Creabilis Medical Officer prior to breaking the blind. Reason for breaking the blind was to be documented in the IWRS system and the study case report form. The blind was not broken early for any subjects in this study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Treatment Group 1
    Arm description
    		 0.05% w/w CT327 ointment
    Arm type
    		 Experimental

    Investigational medicinal product name
    CT327
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    Subjects received twice-daily topical applications of 0.05% w/w CT327 ointment for up to 4 weeks.

    Arm title
    		 Treatment Group 2
    Arm description
    		 0.5% w/w CT327 ointment
    Arm type
    		 Experimental

    Investigational medicinal product name
    CT327
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    Subjects received twice-daily topical applications of 0.5% w/w CT327 ointment for up to 4 weeks.

    Arm title
    		 Treatment Group 3
    Arm description
    		 Vehicle (ointment containing no CT327)
    Arm type
    		 Placebo

    Investigational medicinal product name
    CT327 Vehicle
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    Subjects received twice-daily applications of CT327 vehicle (ointment containing no CT327) for up to 4 weeks.

    Number of subjects in period 1
    		Treatment Group 1 Treatment Group 2 Treatment Group 3
    Started
    62
    63
    63
    Completed
    50
    43
    53
    Not completed
    12
    20
    10
         Consent withdrawn by subject
    3
    4
    1
         Adverse event, non-fatal
    7
    5
    4
         Other
    -
    1
    1
         Lost to follow-up
    1
    6
    2
         Protocol deviation
    1
    -
    -
         Lack of efficacy
    -
    4
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Treatment Group 1
    Reporting group description
    		 0.05% w/w CT327 ointment

    Reporting group title
    Treatment Group 2
    Reporting group description
    		 0.5% w/w CT327 ointment

    Reporting group title
    Treatment Group 3
    Reporting group description
    		 Vehicle (ointment containing no CT327)

    Reporting group values
    		 Treatment Group 1 Treatment Group 2 Treatment Group 3 Total
    Number of subjects
    		 62 63 63 188
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 10 10 9 29
        Adults (18-64 years)
    		 47 48 52 147
        From 65-84 years
    		 5 5 2 12
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 34.0 ± 16.51 30.8 ± 15.78 31.7 ± 15.01 -
    Gender categorical
    Units: Subjects
        Female
    		 30 39 36 105
        Male
    		 32 24 27 83

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Treatment Group 1
    Reporting group description
    		 0.05% w/w CT327 ointment

    Reporting group title
    Treatment Group 2
    Reporting group description
    		 0.5% w/w CT327 ointment

    Reporting group title
    Treatment Group 3
    Reporting group description
    		 Vehicle (ointment containing no CT327)

    Primary: Controlled disease response rate

    		 Close Top of page
    End point title
    		 Controlled disease response rate
    End point description
    Binary response defined as a score of “clear” (0) or “almost clear” (1) on the Investigator Global Assessment or a minimum improvement of 2 categories
    End point type
    Primary
    End point timeframe
    From Day 1 (baseline) to Day 29 (end of treatment visit)
    End point values
    		 Treatment Group 1 Treatment Group 2 Treatment Group 3
    Number of subjects analysed
    62
    63
    63
    Units: Percentage of subjects
        number (not applicable)
    17.7
    20.6
    25.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The study used a sequentially rejective test procedure to provide strong control of the familywise error rate (FWER) at level α=0.05, while testing the two primary endpoints at both dose levels.
    Comparison groups
    Treatment Group 3 v Treatment Group 1
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 1.5
    Notes
    [1] - The CT327 0.5% treatment group controlled disease response rate was not statistically significantly different from vehicle, at the 2.5% significance level required by the sequentially rejective test procedure. As such, in accordance with the test procedure, no testing was conducted for the CT327 0.05% group.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The study used a sequentially rejective test procedure to provide strong control of the familywise error rate (FWER) at level α=0.05, while testing the two primary endpoints at both dose levels.
    Comparison groups
    Treatment Group 2 v Treatment Group 3
    Number of subjects included in analysis
    126
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.025 [2]
    Method
    		 Chi-squared
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 1.76
    Notes
    [2] - p=0.5255

    Primary: Change from baseline in average pruritus visual analogue scale (VAS) score

    		 Close Top of page
    End point title
    		 Change from baseline in average pruritus visual analogue scale (VAS) score
    End point description
    End point type
    Primary
    End point timeframe
    From Day 1 (baseline visit) to Day 29 (end of treatment visit)
    End point values
    		 Treatment Group 1 Treatment Group 2 Treatment Group 3
    Number of subjects analysed
    62
    63
    63
    Units: Score on a scale
        least squares mean (standard error)
    -21.7 ± 3.21
    -19.1 ± 3.20
    -25.2 ± 3.17
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The study used a sequentially rejective test procedure to provide strong control of the familywise error rate (FWER) at level α=0.05, while testing the two primary endpoints at both dose levels.
    Comparison groups
    Treatment Group 1 v Treatment Group 3
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 12.4
    Notes
    [3] - The CT327 0.5% treatment group was not statistically significantly different from vehicle at Day 29, at the 2.5% significance level required by the sequentially rejective test procedure. As such, in accordance with the test procedure, no testing was conducted for the CT327 0.05% group.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The study used a sequentially rejective test procedure to provide strong control of the familywise error rate (FWER) at level α=0.05, while testing the two primary endpoints at both dose levels.
    Comparison groups
    Treatment Group 2 v Treatment Group 3
    Number of subjects included in analysis
    126
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.025 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.87
         upper limit
    		 14.95
    Notes
    [4] - p=0.182

    Secondary: EASI-50 Response Rate

    		 Close Top of page
    End point title
    		 EASI-50 Response Rate
    End point description
    Binary response defined as a reduction of 50% or more from baseline on the Eczema Area and Severity Index score
    End point type
    Secondary
    End point timeframe
    From baseline to Day 29
    End point values
    		 Treatment Group 1 Treatment Group 2 Treatment Group 3
    Number of subjects analysed
    62
    63
    63
    Units: Percentage of subjects
        number (not applicable)
    37.1
    39.7
    42.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The frequency count and percentage of subjects with an EASI-50 response along with the associated 95% confidence interval were summarised by treatment and visit.
    Comparison groups
    Treatment Group 1 v Treatment Group 3
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.05 [5]
    Method
    		 Chi-squared
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 1.61
    Notes
    [5] - p=0.5110
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The frequency count and percentage of subjects with an EASI-50 response along with the associated 95% confidence interval were summarised by treatment and visit.
    Comparison groups
    Treatment Group 2 v Treatment Group 3
    Number of subjects included in analysis
    126
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.05 [6]
    Method
    		 Chi-squared
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 1.78
    Notes
    [6] - p=0.7174

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from Visit 1 (Day 1) to Visit 7 (14 [plus/minus 3] days from last treatment [Day 29]).
    Adverse event reporting additional description
    An adverse event was defined as any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product. The term also covers clinical laboratory findings that were considered to be clinically relevant.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Treatment Group 1
    Reporting group description
    		 0.05% w/w CT327 ointment

    Reporting group title
    Treatment Group 2
    Reporting group description
    		 0.5% w/w CT327 ointment

    Reporting group title
    Treatment Group 3
    Reporting group description
    		 Vehicle (ointment containing no CT327)

    Serious adverse events
    		 Treatment Group 1 Treatment Group 2 Treatment Group 3
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 62 (0.00%)
    3 / 63 (4.76%)
    0 / 63 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Asthma
    Additional description: An 18-year-old female was hospitalised due to an exacerbation of her asthma on Day 9 of study treatment. The subject was withdrawn from the study as she was given oral prednisone, which could have affected the study efficacy assessment.
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 63 (1.59%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dysphagia
    Additional description: A 66-year-old male subject who was hospitalised due to dysphagia. The subject continued study medication and completed the 4-week treatment period.
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 63 (1.59%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
    Additional description: A 65-year-old male with a history of heart disease was hospitalised due to musculoskeletal pain, which was originally believed to be a myocardial infarction. The subject continued study medication and completed the 4-week treatment period.
         subjects affected / exposed
    0 / 62 (0.00%)
    1 / 63 (1.59%)
    0 / 63 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Treatment Group 1 Treatment Group 2 Treatment Group 3
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    37 / 62 (59.68%)
    40 / 63 (63.49%)
    32 / 63 (50.79%)
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    9 / 62 (14.52%)
    11 / 63 (17.46%)
    4 / 63 (6.35%)
         occurrences all number
    11
    11
    4
    Pruritus
         subjects affected / exposed
    5 / 62 (8.06%)
    5 / 63 (7.94%)
    3 / 63 (4.76%)
         occurrences all number
    5
    5
    3
    Dermatitis atopic
         subjects affected / exposed
    3 / 62 (4.84%)
    4 / 63 (6.35%)
    6 / 63 (9.52%)
         occurrences all number
    3
    4
    6
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 62 (6.45%)
    0 / 63 (0.00%)
    2 / 63 (3.17%)
         occurrences all number
    5
    0
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jun 2013
    The adult patient information sheet was originally intended for use by subjects ≥18 years. Subjects aged 12-17 years were to provide assent, whilst consent was obtained from the parent or legal guardian. As this was not in line with the National Research Ethics Service guidance, the protocol was updated to allow any subjects aged ≥16 years to be consented, whilst those aged 12-15 provided assent and required parental/guardian consent. Sections 6.1 and 10.6 of the protocol were amended to reflect this change.
    07 Feb 2014
    On review of the original sample size calculations, the sponsor estimated that a reduced number of patients would allow the study to attain sufficient power to test the primary hypothesis. The original number of 70 completed subjects in each treatment group (210 subjects in total) was chosen to provide at least 85% power for both primary endpoints. A reduction in subject numbers to 60 completed subjects in each treatment group (180 subjects in total) was estimated to provide at least 80% power for both primary endpoints. Also, regulatory feedback and further definition of the CT327 phase 3 programme confirmed that additional pivotal confirmatory trials in this indication would be required. Therefore a powering of 80% is more than acceptable for this current study, than the prior conservative powering of at least 85%. The reduction in power was considered acceptable from a statistical standpoint, and it was deemed ethically appropriate to reduce the patient numbers exposed to investigational medical product to address the primary hypothesis.

    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, 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-Fri Apr 26 21:39:43 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA