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   43874   clinical trials with a EudraCT protocol, of which   7294   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:
    Exploratory study of the efficacy and safety of topical bimiralisib in an inflammatory and hyperproliferative skin condition

    Summary
    EudraCT number
    		 2019-001189-14
    Trial protocol
    		 FR  
    Global end of trial date
    16 Mar 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Oct 2020
    First version publication date
    09 Oct 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PQR309-401
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    PIQUR Therapeutics AG
    Sponsor organisation address
    Hochbergerstrasse 60C, Basel, Switzerland, CH-4057
    Public contact
    Clinical Program Leader, PIQUR Therapeutics AG, info@piqur.com
    Scientific contact
    Clinical Program Leader, PIQUR Therapeutics AG, info@piqur.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
    18 Mar 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Mar 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Mar 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of three concentrations of topical bimiralisib compared to matching vehicle and two approved topical medications (Daivobet® and Daivonex®) applied once daily to distinct 2 cm diameter treatment mini-zones on each patient.
    Protection of trial subjects
    The study processes, potential benefits and any risks of participating in the study were explained to each patient. Patients were continuously monitored by the clinical investigators via regular study visits throughout the duration of the study. If the study drug needed to be stopped for safety, then the responsible investigator would continue to monitor the patient`s health and determine what treatment should be given (if any) until the symptoms or findings had resolved or until a satisfactory conclusion was reached.
    Background therapy
    		 Not applicable.
    Evidence for comparator
    		 Two active comparators were used: Daivobet ointment and Daivonex ointment. Daivobet contains two active substances: calcipotriol and betamethasone. The vitamin D derivative, Calcipotriol, acts through receptors prevent skin proliferation that causes the scaly patches in psoriasis. Betamethasone is an anti-inflammatory that helps reduce the inflammation and itching that occur with psoriasis. Daivonex contains only calcipotriol. Both medicinal products have been approved for over 15 years for topical treatment of plaque psoriasis and have previously been used as positive comparators in the established 4-week Psoriasis Plaque Test (PPT), which formed the basis of the current study.
    Actual start date of recruitment
    12 Nov 2019
    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
    France: 24
    Worldwide total number of subjects
    24
    EEA total number of subjects
    24
    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)
    21
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients were recruited from 12-Nov-2019 until 15-Jan-2020 to one clinical site in Nice, France.

    Pre-assignment
    Screening details
    		 In total 26 patients were screened, of which 24 were enrolled in the study. Two patients were not enrolled because they did not meet inclusion criteria (07 and 09, respectively).

    Period 1
    Period 1 title
    Treatment Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Investigator [1]
    Blinding implementation details
    The study was not double-blinded as the two commercially-available active comparators were distinguishable from the other IMPs. However, the study was considered investigator-blinded since IMP applications were performed out of sight of the investigator/evaluator.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Vehicle
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Vehicle (non-aqueous gel)
    Investigational medicinal product code
    N/A
    Other name
    Pharmaceutical forms
    Gel
    Routes of administration
    Topical use
    Dosage and administration details
    50 µL vehicle was administered once daily for six consecutive days per week for four weeks (24 applications) on a 2-cm diameter mini-zone.

    Arm title
    		 Bimiralisib 0.5% (w/w)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    bimiralisib 0.5% (w/w) gel
    Investigational medicinal product code
    PQR309
    Other name
    Pharmaceutical forms
    Gel
    Routes of administration
    Topical use
    Dosage and administration details
    50 µL bimiralisib 0.5% (w/w) non-aqueous gel was administered once daily for six consecutive days per week for four weeks (24 applications) on a 2-cm diameter mini-zone.

    Arm title
    		 Bimiralisib 2.0% (w/w)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    bimiralisib 2.0% (w/w) gel
    Investigational medicinal product code
    PQR309
    Other name
    Pharmaceutical forms
    Gel
    Routes of administration
    Topical use
    Dosage and administration details
    50 µL bimiralisib 2.0% (w/w) non-aqueous gel was administered once daily for six consecutive days per week for four weeks (24 applications) on a 2-cm diameter mini-zone.

    Arm title
    		 Bimiralisib 6.3% (w/w)
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    bimiralisib 6.3% (w/w) gel
    Investigational medicinal product code
    PQR309
    Other name
    Pharmaceutical forms
    Gel
    Routes of administration
    Topical use
    Dosage and administration details
    50 µL bimiralisib 6.3% (w/w) non-aqueous gel was administered once daily for six consecutive days per week for four weeks (24 applications) on a 2-cm diameter mini-zone.

    Arm title
    		 Daivobet
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Daivobet ointment
    Investigational medicinal product code
    Other name
    Betamethasone (as dipropionate) 0.5mg/g + Calcipotriol 50µg/g
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    50 µL Daivobet ointment (betamethasone (as dipropionate) 0.5mg/g + calcipotriol 50µg/g) was administered once daily for six consecutive days per week for four weeks (24 applications) on a 2-cm diameter mini-zone.

    Arm title
    		 Daivonex
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Daivonex ointment
    Investigational medicinal product code
    Other name
    Calcipotriol 50µg/g
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    50 µL Daivonex ointment (calcipotriol 50µg/g) was administered once daily for six consecutive days per week for four weeks (24 applications) on a 2-cm diameter mini-zone.

    Notes
    [1] - The roles blinded appear inconsistent with a simple blinded trial.
    Justification: The study was designed as an investigator-blinded, within-patient randomised, intra-individual comparison of treatments. Hence each patient received all study treatments which were randomly allocated to one of six mini-zones selected on psoriasis plaques of identical severity. During the study, the patient and person dispensing IMP were instructed not to discuss study products with the investigator who performed evaluations.
    Number of subjects in period 1
    		Vehicle Bimiralisib 0.5% (w/w) Bimiralisib 2.0% (w/w) Bimiralisib 6.3% (w/w) Daivobet Daivonex
    Started
    24
    24
    24
    24
    24
    24
    Completed
    24
    24
    24
    24
    24
    24

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Treatment Period
    Reporting group description
    		 -

    Reporting group values
    		 Treatment Period Total
    Number of subjects
    		 24 24
    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)
    		 21 21
        From 65-84 years
    		 3 3
        85 years and over
    		 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 56.5 (32 to 79) -
    Gender categorical
    Units: Subjects
        Female
    		 7 7
        Male
    		 17 17
    Skin type
    Skin type according to Fitzpatrick's classification
    Units: Subjects
        Type II
    		 2 2
        Type III
    		 20 20
        Type IV
    		 2 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Vehicle
    Reporting group description
    		 -

    Reporting group title
    Bimiralisib 0.5% (w/w)
    Reporting group description
    		 -

    Reporting group title
    Bimiralisib 2.0% (w/w)
    Reporting group description
    		 -

    Reporting group title
    Bimiralisib 6.3% (w/w)
    Reporting group description
    		 -

    Reporting group title
    Daivobet
    Reporting group description
    		 -

    Reporting group title
    Daivonex
    Reporting group description
    		 -

    Primary: AUEC of Total Clinical Score

    		 Close Top of page
    End point title
    		 AUEC of Total Clinical Score
    End point description
    The primary efficacy endpoint was the Area Under the Effect Curve (AUEC) of Total Clinical Score (TCS) calculated from Day 1 to Day 29 using the trapezoidal rule. The lower the AUEC1-29, the stronger is the activity of the drug. TCS was defined in the protocol as the sum of psoriasis severity index scores of erythema, scaling and induration.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 29
    End point values
    		 Vehicle Bimiralisib 0.5% (w/w) Bimiralisib 2.0% (w/w) Bimiralisib 6.3% (w/w) Daivobet Daivonex
    Number of subjects analysed
    24
    24
    24
    24
    24
    24
    Units: Score
        arithmetic mean (standard deviation)
    170.69 ( 33.51 )
    157.65 ( 44.04 )
    160.92 ( 31.46 )
    171.31 ( 37.66 )
    58.31 ( 19.00 )
    92.52 ( 27.05 )
    Statistical analysis title
    		 Analysis of AUEC1-29 of the TCS
    Statistical analysis description
    The AUEC1-29 of the TCS was analyzed using a mixed-effect model. This model included treatment as fixed effect and subject as random effect. The treatments were compared using the Tukey Kramer multiple comparison test performed at a 5% two-sided significance level.
    Comparison groups
    Vehicle v Bimiralisib 0.5% (w/w) v Bimiralisib 2.0% (w/w) v Bimiralisib 6.3% (w/w) v Daivobet v Daivonex
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Variability estimate
    Standard deviation

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    The analysis of adverse events (AEs) is based on treatment emergent adverse events (TEAEs), defined as all AEs occurring or worsening after first dose of IMP.
    Adverse event reporting additional description
    Safety assessments were conducted for all patients at the screening visit (following ICF signature) and at every subsequent visit. Safety parameters were: 1) Local tolerance assessed twice weekly using a 4-point scale for each mini-zone, and 2) Monitoring and recording of AEs.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Safety Population
    Reporting group description
    		 All randomized patients who received at least one dose of the study products (i.e. either test or reference products).

    Serious adverse events
    		 Safety Population
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Safety Population
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 24 (16.67%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 24 (4.17%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 24 (8.33%)
         occurrences all number
    2
    Infections and infestations
    Paronychia
         subjects affected / exposed
    1 / 24 (4.17%)
         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.
    This study involved an intra-individual comparison of treatments therefore each patient received each of the five IMPs randomized to five treatment mini-zones. The total number of patients in the analysis was thus 24 (and not 144).
    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 17 05:57:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA