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    Clinical Trial Results:
    An open-label, single arm, Phase III study to assess the self-administration of AOP2014 using a pre-filled pen, developed for the treatment of Polycythemia Vera patients

    Summary
    EudraCT number
    		 2014-001356-31
    Trial protocol
    		 HU   SK   AT   CZ   BG   PL  
    Global end of trial date
    21 Dec 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Mar 2018
    First version publication date
    11 Mar 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    PEN-PV
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AOP Orphan Pharmaceuticals AG
    Sponsor organisation address
    Wilhelminenstrasse 91/II f/B4, Vienna, Austria, 1160
    Public contact
    Head of Clinical Operations, AOP Orphan Pharmaceuticals AG, +43 15037244 46, michael.zoerer@aoporphan.com
    Scientific contact
    Head of Clinical Operations, AOP Orphan Pharmaceuticals AG, +43 15037244 46, michael.zoerer@aoporphan.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
    19 Jan 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Dec 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Dec 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the ease of AOP2014 self-administration using dedicated questionnaires.
    Protection of trial subjects
    An independent DMC was established that reviewed accumulated data on safety as well as efficacy in an open-label manner in regular intervals. Following the meetings the DMC advised the sponsor in writing on outcomes and findings of the meeting. Per the signed DMC charter the DMC took responsibility for continued safety as well as efficacy oversight.
    Background therapy
    		 Low dose aspirin (acetylsalicylic acid) (100 mg/day) administered to all patients for the duration of study treatment, unless contraindicated.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 Jun 2015
    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
    Poland: 4
    Country: Number of subjects enrolled
    Slovakia: 1
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    Bulgaria: 10
    Country: Number of subjects enrolled
    Czech Republic: 5
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Ukraine: 6
    Worldwide total number of subjects
    36
    EEA total number of subjects
    30
    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)
    24
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 From patients who had completed the AOP2014 arm of the PROUD-PV study or were participating in the CONTINUATION-PV study, 36 subjects were chosen according to the inclusion and exclusion criteria.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 AOP2014 administration via pen
    Arm description
    		 AOP2014 self-administered via a pre-filled pen at the individualized dose which delivers the optimal disease response.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AOP2014
    Investigational medicinal product code
    AOP2014
    Other name
    Pegylated Proline-Interferon α-2b
    Pharmaceutical forms
    Solution for injection/infusion in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    AOP2014 was self-administered using a pre-filled pen every 14 days at the individualized dose delivering the optimal disease response (Haematocrit<45%, Platelets <400 x 109/L and White blood cells <10 x 109/L), as determined previously during the PROUD-PV Study and maintained for the CONTINUATION-PV Study.

    Number of subjects in period 1
    		AOP2014 administration via pen
    Started
    36
    Completed
    36

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 36 36
    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)
    		 24 24
        From 65-84 years
    		 12 12
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.5 ± 9.99 -
    Gender categorical
    Units: Subjects
        Female
    		 13 13
        Male
    		 23 23
    Duration of AOP treatment at the start of the study
    Units: months
        arithmetic mean (standard deviation)
    		 15.65 ± 2.596 -

    End points

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    End points reporting groups
    Reporting group title
    AOP2014 administration via pen
    Reporting group description
    		 AOP2014 self-administered via a pre-filled pen at the individualized dose which delivers the optimal disease response.

    Primary: Evaluation of ease of self-administration based on questionnaire A and B

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    End point title
    		 Evaluation of ease of self-administration based on questionnaire A and B [1]
    End point description
    Full success was declared if questions "Experience any technical problems with the pen during the injection?" and "Withdraw the pen before the injection was complete, as evidenced by the supervising Investigator?") where answered ‘No’.
    End point type
    Primary
    End point timeframe
    Evaluated according to questionnaire answered by investigators at visits with supervised study treatment self-administration.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned.
    End point values
    		 AOP2014 administration via pen
    Number of subjects analysed
    36
    Units: subjects
        Visit 1 - Full success
    29
        Visit 2 - Full success
    33
        Visit 7 - Fullsuccess
    36
    No statistical analyses for this end point

    Primary: Failure rate - Questionnaire A

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    End point title
    		 Failure rate - Questionnaire A [2]
    End point description
    Failure rate (%) is calculated as (actual score/highest score)*100.
    End point type
    Primary
    End point timeframe
    Evaluated according to questionnaire answered by investigators at visits with supervised study treatment self-administration.
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned to evaluate if objective defined below was met. • To achieve < 34.0% failure rate at supervised self-administration 1 (Visit 1) for both questionnaires • To achieve <17.0% failure rate at supervised self-administration 2 (Visit 2) for both questionnaires • Failure rate < 50.0% for each questionnaire at all subsequent visits
    End point values
    		 AOP2014 administration via pen
    Number of subjects analysed
    36
    Units: percent
    arithmetic mean (standard deviation)
        Visit 1
    13.1 ± 15.788
        Visit 2
    5.95 ± 12.489
        Visit 7
    0 ± 0
    No statistical analyses for this end point

    Primary: Failure rate - Questionnaire B

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    End point title
    		 Failure rate - Questionnaire B [3]
    End point description
    Failure rate (%) is calculated as (actual score/highest score)*100.
    End point type
    Primary
    End point timeframe
    Evaluated according to questionnaire answered by patient at each study treatment self-administration.
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were planned to evaluate if objective defined below was met. • To achieve < 34.0% failure rate at supervised self-administration 1 (Visit 1) for both questionnaires • To achieve <17.0% failure rate at supervised self-administration 2 (Visit 2) for both questionnaires • Failure rate < 50.0% for each questionnaire at all subsequent visits
    End point values
    		 AOP2014 administration via pen
    Number of subjects analysed
    36
    Units: percent
    arithmetic mean (standard deviation)
        Visit 1
    6.94 ± 13.437
        Visit 2
    0.46 ± 2.778
        Visit 3
    0.93 ± 3.872
        Visit 4
    0 ± 0
        Visit 5
    0.46 ± 2.778
        Visit 6
    0 ± 0
        Visit 7
    0 ± 0
    No statistical analyses for this end point

    Secondary: Number of responders by visit

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    End point title
    		 Number of responders by visit
    End point description
    Disease response (haematological response with spleen normality) was defined as: • Haematocrit < 45% without phlebotomy (at least 3 months since the last phlebotomy). • Platelets < 400 x 109/L. • White blood cells < 10 x 109/L. • Normal spleen size.
    End point type
    Secondary
    End point timeframe
    Disease response rate evaluated at first (visit 1) and last (visit 7) study visit.
    End point values
    		 AOP2014 administration via pen
    Number of subjects analysed
    36
    Units: subjects
        Visit 1
    15
        Visit 7
    17
    No statistical analyses for this end point

    Secondary: Number of haematological responders by visit

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    End point title
    		 Number of haematological responders by visit
    End point description
    Disease response (haematological response) was defined as: • Haematocrit < 45% without phlebotomy (at least 3 months since the last phlebotomy). • Platelets < 400 x 109/L. • White blood cells < 10 x 109/L.
    End point type
    Secondary
    End point timeframe
    Disease response rate (without spleen size) evaluated at first (visit 1) and last (visit 7) study visit.
    End point values
    		 AOP2014 administration via pen
    Number of subjects analysed
    36
    Units: subjects
        Visit 1
    26
        Visit 7
    27
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events occurring during the course of the clinical study were collected.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 Treatment emergent adverse events that started in PEN-PV.

    Serious adverse events
    		 Overall trial
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 36 (2.78%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Overall trial
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 36 (38.89%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    3 / 36 (8.33%)
         occurrences all number
    3
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    4 / 36 (11.11%)
         occurrences all number
    4
    Thrombocytopenia
         subjects affected / exposed
    3 / 36 (8.33%)
         occurrences all number
    4
    Anaemia
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    General disorders and administration site conditions
    Facial pain
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    2
    Chest pain
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Fatigue
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Diarrhoea
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Rectal fissure
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Rhinitis atrophic
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    2
    Skin and subcutaneous tissue disorders
    Erythrosis
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Psychiatric disorders
    Affective disorder
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Anxiety
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Mood swings
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Nervousness
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Renal and urinary disorders
    Calculus urinary
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    2
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    2
    Cystitis
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Infection
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Rhinitis
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Viraemia
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1

    More information

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    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.
    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.

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