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   43871   clinical trials with a EudraCT protocol, of which   7290   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:
    Apremilast as anti-pruritic treatment in patients with prurigo nodularis

    Summary
    EudraCT number
    		 2016-003018-29
    Trial protocol
    		 DK  
    Global end of trial date
    27 Feb 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Feb 2020
    First version publication date
    08 Feb 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    2016-003018-29
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Dept of Dermatology and Allergy, Herlev and Gentofte Hospital
    Sponsor organisation address
    Gentofte Hospitalsvej 15, Hellerup, Denmark, 2900
    Public contact
    Dept of Dermatology and Allergy, Herlev and Gentofte Hospital, 0045 38673203, claus.zachariae@regionh.dk
    Scientific contact
    Dept of Dermatology and Allergy, Herlev and Gentofte Hospital, 0045 38673203, claus.zachariae@regionh.dk
    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
    01 Oct 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Feb 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Feb 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study will evaluate the anti-pruritic effect of apremilast in patients with known PN. 1) Reduction in mean absolute VAS-pruritus score after 12 weeks treatment with apremilast compared to mean VAS-pruritus score before treatment with apremilast
    Protection of trial subjects
    This study was established as a pilot study with no placebo controlled group as patients with prurigo nodularis (PN) suffer from severe pruritus. There fore it would be unethical to placebo treat these patients. Patients were provided with written and oral information of this study and were enrolled when given their written informed consent. The study was designed in accordance to the Helsinki-declaration. Herlev and Gentofte Hospital will ensure that collection and processing of personal data are in compliance with national legislation on data protection and privacy. Patients were treated with apremilast, which is an approved drug for psoriasis and PsA. The drug is demonstrated to be safe and well tolerated and with low side-effects and is used for patients with psoriasis in the daily clinic at the Department of Dermatology and Allergy, Herlev and Gentofte Hospital.
    Background therapy
    		 -
    Evidence for comparator
    		 Single arm. No comparators were used
    Actual start date of recruitment
    30 Jun 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Denmark: 10
    Worldwide total number of subjects
    10
    EEA total number of subjects
    10
    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)
    0
    Adults (18-64 years)
    5
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patient with moderate to severe PN were recruited from the department of Dermatology and Allergy Main criteria for inclusion • > 18 years of age • PN verified diagnosis by characteristic clinical features • Moderate to severe PN • Failure of local steroid and light treatment to control disease and symptoms.

    Pre-assignment
    Screening details
    		 Failure to topical therapy and UV therapy Blood samples, chest x-ray, urin test for pregnancy/infection

    Pre-assignment period milestones
    Number of subjects started
    		 10
    Number of subjects completed
    		 10

    Period 1
    Period 1 title
    overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not blinded. All participants received the same treatment

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Apremilast treatment
    Arm description
    		 apremilast 30 mg x 2 daily, initially a titration period of 6 days. Total treatment period is 12 weeks
    Arm type
    		 Single arm

    Investigational medicinal product name
    apremilast
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Apremilast was titrated from 10 mg x 1 (day 1), 10 mg x 2 (day 2), 10 + 20 mg (day 3), 20 x 2 mg (day 4), 20 + 30 mg (day 5) to 30 mg x 2 (day 6) corresponding to recommended daily dose for psoriasis treatment. Total treatment period was 12 weeks, with patients administering the medication at home.

    Arm title
    		 Baseline pre-treatment
    Arm description
    		 Pre-treatment as advised in guidance dated - EudraCT FAQ v1.4 May 2019: Currently the system cannot accommodate this specific scenario. Hence, you can proceed with a workaround whereby the baseline is considered one group and the end data another group. By doing that you will be able to use the statistical analysis set to report analysis for a single arm.
    Arm type
    		 baseline

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Unknown use
    Dosage and administration details
    No investigational medicinal product assigned in this arm

    Investigational medicinal product name
    apremilast
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Apremilast was titrated from 10 mg x 1 (day 1), 10 mg x 2 (day 2), 10 + 20 mg (day 3), 20 x 2 mg (day 4), 20 + 30 mg (day 5) to 30 mg x 2 (day 6) corresponding to recommended daily dose for psoriasis treatment. Total treatment period was 12 weeks, with patients administering the medication at home.

    Number of subjects in period 1
    		Apremilast treatment Baseline pre-treatment
    Started
    10
    10
    Completed
    7
    7
    Not completed
    3
    3
         Lack of efficacy
    3
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    overall period
    Reporting group description
    		 -

    Reporting group values
    		 overall period Total
    Number of subjects
    		 10 10
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 5 5
        From 65-84 years
    		 5 5
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.7 ± 10.0 -
    Gender categorical
    Units: Subjects
        Female
    		 5 5
        Male
    		 5 5
    Subject analysis sets

    Subject analysis set title
    Intervention
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intervention, apremilast

    Subject analysis sets values
    		 Intervention
    Number of subjects
    10
    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)
    5
        From 65-84 years
    5
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    61.7 ± 10.0
    Gender categorical
    Units: Subjects
        Female
    5
        Male
    5

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Apremilast treatment
    Reporting group description
    		 apremilast 30 mg x 2 daily, initially a titration period of 6 days. Total treatment period is 12 weeks

    Reporting group title
    Baseline pre-treatment
    Reporting group description
    		 Pre-treatment as advised in guidance dated - EudraCT FAQ v1.4 May 2019: Currently the system cannot accommodate this specific scenario. Hence, you can proceed with a workaround whereby the baseline is considered one group and the end data another group. By doing that you will be able to use the statistical analysis set to report analysis for a single arm.

    Subject analysis set title
    Intervention
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intervention, apremilast

    Primary: VAS-pruritus

    		 Close Top of page
    End point title
    		 VAS-pruritus
    End point description
    Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in VAS pruritus ≥ 3 points
    End point type
    Primary
    End point timeframe
    16 weeks
    End point values
    		 Apremilast treatment Baseline pre-treatment Intervention
    Number of subjects analysed
    10
    10
    10
    Units: VAS-pruritus
    10
    10
    10
    Attachments
    		 Change in VAS pruritus
    Statistical analysis title
    		 Descriptive
    Statistical analysis description
    Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in VAS pruritus ≥ 3 points
    Comparison groups
    Apremilast treatment v Baseline pre-treatment
    Number of subjects included in analysis
    20
    Analysis specification
    Post-hoc
    Analysis type
    		 other [1]
    P-value
    		 = 99999 [2]
    Method
    		 N/A
    Confidence interval
    Notes
    [1] - Descriptive
    [2] - 99999 = N/A

    Secondary: Change in PGA

    		 Close Top of page
    End point title
    		 Change in PGA
    End point description
    Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in in PGA ≥ 2 points
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Apremilast treatment Baseline pre-treatment Intervention
    Number of subjects analysed
    10
    10
    10
    Units: 0-4
        number (not applicable)
    10
    10
    10
    Attachments
    		 Change in PGA
    Statistical analysis title
    		 descriptive
    Statistical analysis description
    descriptive
    Comparison groups
    Baseline pre-treatment v Apremilast treatment
    Number of subjects included in analysis
    20
    Analysis specification
    Post-hoc
    Analysis type
    		 other [3]
    P-value
    		 = 99999 [4]
    Method
    		 N/A
    Confidence interval
    Notes
    [3] - Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in in PGA ≥ 2 points
    [4] - 99999 = N/A

    Secondary: PaGA

    		 Close Top of page
    End point title
    		 PaGA
    End point description
    Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in PaGA ≥ 2 points.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Apremilast treatment Baseline pre-treatment Intervention
    Number of subjects analysed
    10
    10
    10
    Units: 0-5
        number (not applicable)
    10
    10
    10
    Attachments
    		 Change in PaGA
    Statistical analysis title
    		 Descriptive
    Statistical analysis description
    Descriptive
    Comparison groups
    Apremilast treatment v Baseline pre-treatment
    Number of subjects included in analysis
    20
    Analysis specification
    Post-hoc
    Analysis type
    		 other [5]
    P-value
    		 = 99999 [6]
    Method
    		 N/A
    Confidence interval
    Notes
    [5] - Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in PaGA ≥ 2 points.
    [6] - 99999 = N/A

    Secondary: DLQI

    		 Close Top of page
    End point title
    		 DLQI
    End point description
    Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in DLQI ≥ 4 points
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Apremilast treatment Baseline pre-treatment Intervention
    Number of subjects analysed
    10
    10
    10
    Units: 0-30
        number (not applicable)
    10
    10
    10
    Attachments
    		 Change in DLQI
    Statistical analysis title
    		 Descriptive
    Statistical analysis description
    Descriptive
    Comparison groups
    Apremilast treatment v Intervention
    Number of subjects included in analysis
    20
    Analysis specification
    Post-hoc
    Analysis type
    		 other [7]
    P-value
    		 = 99999 [8]
    Method
    		 N/A
    Confidence interval
    Notes
    [7] - Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in DLQI ≥ 4 points
    [8] - 99999 = N/A

    Secondary: PSQI

    		 Close Top of page
    End point title
    		 PSQI
    End point description
    Responders were considered as those receiving the minimally important difference/minimally clinically important difference at week 12 compared to baseline defined as a difference in PSQI ≥ 3 points
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Apremilast treatment Baseline pre-treatment
    Number of subjects analysed
    10
    10
    Units: 0-21
        number (not applicable)
    10
    10
    Statistical analysis title
    		 Descriptive
    Statistical analysis description
    Descriptive
    Comparison groups
    Apremilast treatment v Baseline pre-treatment
    Number of subjects included in analysis
    20
    Analysis specification
    Post-hoc
    Analysis type
    		 other
    P-value
    		 = 9999999 [9]
    Method
    		 N/A
    Confidence interval
    Notes
    [9] - 99999 = N/A

    Secondary: Cytokine expression

    		 Close Top of page
    End point title
    		 Cytokine expression
    End point description
    Additionally, a secondary endpoint was to evaluate changes in cytokine and chemokine expression detected by real-time quantitative polymerase chain reaction (RT qPCR) analyses.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Apremilast treatment Baseline pre-treatment Intervention
    Number of subjects analysed
    7
    7
    7
    Units: various
    7
    7
    7
    Attachments
    		 Change in IL-31
    Statistical analysis title
    		 wilcoxon/mann-whitney
    Statistical analysis description
    Cytokine and chemokine concentrations at week 4 and week 12 were compared with baseline concentrations by use of Wilcoxon signed rank-test. Concentration of IL-31 at week 4 and week 12 was compared with baseline concentration by use of Mann-Whitney test due to missing data for IL-31. Values of P < 0.05 were considered significant.
    Comparison groups
    Apremilast treatment v Baseline pre-treatment
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05 [10]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [10] - Values of P < 0.05 were considered significant.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    15-06-2017 to 27-02-2019, baseline, week 2, 4, 12, 16.
    Adverse event reporting additional description
    Adverse event information including dates of event (including onset and resolution), event diagnosis and description, severity, assessment of relatedness to apremilast and action taken was collected at visit 2 (baseline) and at each study visit thereafter.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Apremilast
    Reporting group description
    		 Apremilast intervention group. This is a single arm study.

    Serious adverse events
    		 Apremilast
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 10 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Apremilast
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 10 (50.00%)
    Cardiac disorders
    Chest pain
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    2
    Nervous system disorders
    Headache
    Additional description: Headache
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    5
    General disorders and administration site conditions
    Fever
    Additional description: Fever
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    2
    Gastrointestinal disorders
    Diarrhea
         subjects affected / exposed
    5 / 10 (50.00%)
         occurrences all number
    10
    Nausea
    Additional description: Nausea
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 10 (20.00%)
         occurrences all number
    2
    Restless legs syndrome
         subjects affected / exposed
    1 / 10 (10.00%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    Baseline pre-treatment is provided due to system workaround in single-armed studies (reference: EudraCT FAQ v1.4 May 2019 Item no. 61) 99999 = N/A
    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 May 03 17:51:33 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA