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    The EU Clinical Trials Register currently displays   42758   clinical trials with a EudraCT protocol, of which   7042   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2018-002823-41
    Sponsor's Protocol Code Number:AC-065B302
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-12-20
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2018-002823-41
    A.3Full title of the trial
    A multicenter, randomized, double-blind, placebo-controlled, parallel-group, group-sequential, adaptive, Phase 3 study with open-label extension period to assess the efficacy and safety of selexipag as an add-on to standard of care therapy in subjects with inoperable or persistent/recurrent after surgical and/or interventional treatment Chronic Thromboembolic Pulmonary Hypertension.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study to assess the efficacy and safety of selexipag as an add-on to standard of care therapy in subjects with inoperable or persistent/recurrent, after surgical treatment and/or Chronic Thromboembolic Pulmonary Hypertension (CTEPH).
    A.3.2Name or abbreviated title of the trial where available
    SELECT
    A.4.1Sponsor's protocol code numberAC-065B302
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorActelion Pharmaceuticals Ltd
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportActelion Pharmaceuticals Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationActelion Pharmaceuticals Ltd
    B.5.2Functional name of contact pointClinical Trial Disclosure Desk
    B.5.3 Address:
    B.5.3.1Street AddressGewerbestrasse 16
    B.5.3.2Town/ cityAllschwil
    B.5.3.3Post code4123
    B.5.3.4CountrySwitzerland
    B.5.6E-mailclinical-trials-disclosure@its.jnj.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Uptravi
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSelexipag
    D.3.2Product code ACT-293987
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSELEXIPAG
    D.3.9.2Current sponsor codeACT-293987
    D.3.9.4EV Substance CodeSUB130805
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Thromboembolic Pulmonary Hypertension, inoperable or persistent/recurrent
    E.1.1.1Medical condition in easily understood language
    Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a disease associated with abnormally high pressure in the blood vessels of the lungs, caused by the formation of blood clots.
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10068739
    E.1.2Term Chronic thromboembolic pulmonary hypertension
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to evaluate the effect of selexipag on pulmonary vascular resistance (PVR) versus placebo in subjects with inoperable CTEPH (ie, technically non-operable) and persistent/recurrent CTEPH after surgical (pulmonary endarterectomy [PEA]) and/or interventional (balloon pulmonary angioplasty [BPA]) treatment at Week 20.
    E.2.2Secondary objectives of the trial
    The secondary objectives of the study are to evaluate the effects of selexipag versus placebo on:
    • Exercise capacity.
    • Time to clinical worsening (TTCW).
    • All-cause death or hospitalizations related to PH worsening.
    • WHO FC.
    • Patient-reported outcomes (PROs).
    • Dyspnea.
    • N-terminal pro b-type natriuretic peptide (NT-proBNP).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed and dated Informed Consent Form.

    2. Male and female subjects ≥18 (or the legal age of consent in the jurisdiction in which the study is taking place) and ≤85 years old at Screening (Visit 1).

    3. Subjects with diagnosis of CTEPH and inoperability confirmed by the corresponding Adjudication Committee (AC; Country-specific Adjudication Committee [CSAC] or Central Adjudication Committee [CAC]) [see Section 3.4.3], defined as one of the following options:
    a. Inoperable CTEPH (ie, technically non-operable) with:
    – Diagnosis of CTEPH based on at least two of the following assessments performed in the 14-month period prior to randomization (Visit 2):
    o ventilation/perfusion (V/Q) scan,
    o pulmonary angiography (PA),
    o computed tomography pulmonary angiogram (CTPA), and/or
    o magnetic resonance angiography (MRA).
    – RHC (and LHC, if needed) 1 performed at least 90 days after start of full anticoagulation, showing:
    o PVR at rest ≥400 dyn.sec/cm5 or ≥5 Wood units for the hemodynamic cohort and PVR at rest ≥300 dyn.sec/cm5 or ≥3.75 Wood units for the non-hemodynamic cohort,
    o Mean pulmonary arterial pressure (mPAP) ≥25 mmHg,
    o Pulmonary arterial wedge pressure (PAWP) ≤15 mmHg or, if not available or unreliable, a left ventricular end diastolic pressure (LVEDP) ≤15 mmHg.

    b. Persistent/recurrent CTEPH after BPA, and deemed inoperable with:
    – Diagnosis of CTEPH based on at least one of the following assessments performed in the 14-month period prior to randomization (Visit 2) and after last interventional (BPA) treatment: V/Q scan, PA, CTPA or MRA.
    – RHC (and LHC, if needed)1 performed at least 90 days after last interventional (BPA) treatment and at least 90 days after start of full anticoagulation, showing:
    o PVR at rest ≥400 dyn.sec/cm5 or ≥5 Wood units for the hemodynamic cohort and PVR at rest ≥300 dyn.sec/cm5 or ≥3.75 Wood units for the non-hemodynamic cohort,
    o mPAP ≥25 mmHg,
    o PAWP ≤15 mmHg, or, if not available or unreliable, an LVEDP ≤15 mmHg.

    c. Persistent/recurrent CTEPH after PEA (including PEA followed by BPA) with:
    – Diagnosis of CTEPH based on at least one of the following assessments performed in the 14-month period prior to randomization (Visit 2) and after last surgical (PEA) or interventional (BPA) treatment: V/Q scan, PA, CTPA or MRA.
    – RHC (and LHC, if needed)1 performed at least 90 days after last surgical (PEA) or interventional (BPA) treatment and at least 90 days after start of full anticoagulation, showing:
    o PVR at rest ≥400 dyn.sec/cm5 or ≥5 Wood units for the hemodynamic cohort and PVR at rest ≥300 dyn.sec/cm5 or ≥3.75 Wood units for the non-hemodynamic cohort,
    o mPAP ≥25 mmHg,
    o PAWP ≤15 mmHg, or, if not available or unreliable, an LVEDP ≤15 mmHg.

    4. PH in WHO FC I–IV.

    5. Subject able to perform the 6MWT with a minimum distance of 100 m and a maximum distance of 450 m at Screening Visit (Visit 1).

    6. A woman of childbearing potential [see definition in Section 4.5.1] is eligible only if all the following applies:
    a. Negative serum pregnancy test at Screening and a negative urine pregnancy test at randomization.
    b. Agreement to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation.
    c. Agreement to use one of the methods of birth control described in Section 4.5 from Screening visit up to at least 30 days after study treatment discontinuation.
    E.4Principal exclusion criteria
    General exclusion criteria:
    1. Planned or current treatment with another investigational treatment up to 3 months prior to randomization.
    2. Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease.
    3. Known concomitant life-threatening disease with a life expectancy < 12 months.

    Exclusion criteria related to the disease:
    4. Planned BPA within 26 weeks after randomization.
    5. Change in dose or initiation of new PH-specific therapy within 90 days prior to the baseline RHC (and LHC, if needed) qualifying for enrollment for the hemodynamic cohort and within 90 days prior to randomization (Visit 2) for the non-hemodynamic cohort.
    6. Treatment with prostacyclin (epoprostenol), prostacyclin analogs (ie, treprostinil, iloprost, beraprost) or prostacyclin receptor agonists (ie, selexipag/Uptravi®) within 90 days prior to randomization (Visit 2), except those given at vasodilator testing during RHC.
    7. Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to baseline RHC (and LHC, if needed).

    Exclusion criteria related to comorbidities:
    8. Any co-morbid condition that may influence the ability to perform a reliable and reproducible 6MWT, including use of walking aids (cane, walker, etc).
    9. Other as per selexipag Summary of Product Characteristics (SmPC).

    Exclusion criteria related to selexipag use:
    10. As per selexipag Summary of Product Characteristics (SmPC).
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint of this study is the pulmonary vascular resistance (PVR) at Week 20, assessed at rest, within 2–5 hours post-dose, expressed as percent of baseline PVR.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Assessed at rest in screening period (Day -60 to Day -14; baseline) and assessed at rest within 2–5 hours post-dose at Week 20 during treatment period.
    E.5.2Secondary end point(s)
    1. Change from baseline in 6-minute walk distance (6MWD) to Week 26 (key secondary endpoint).
    2. TTCW (key secondary endpoint), where clinical worsening is defined
    (adapted from the CHMP definition [EMEA 2008]) as at least one of the
    following
    components confirmed by the CEC, when applicable:
    – All-cause death
    – Non-planned PH-related hospitalization
    – PH-related deterioration identified by at least one of the following:
    • Increase from baseline in WHO FC4;
    • Deterioration from baseline by at least 15% in exercise capacity, as measured by the 6MWD4;
    • New or worsening of signs or symptoms of right heart failure, defined as a reported AE with one of the following preferred terms: “CTEPH”, “pulmonary hypertension”, “right ventricular failure”, “right ventricular dysfunction” and “acute right ventricular failure”.

    3. All-cause death or hospitalizations related to PH worsening.
    4.
    Improvement in WHO FC from baseline to Week 26.
    5. Change from baseline to Week 26 in Pulmonary arterial hypertensionsymptoms
    and impact questionnaire (PAH-SYMPACT®) cardiopulmonary
    symptoms domain and cardiovascular symptoms domain.
    6. Change from baseline to Week 26 in Borg dyspnea index (BDI)/Borg CR10®.
    7. Change from baseline to Week 26 in NT-proBNP.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Week 26
    2. end of double blind treatment period
    3. end of double blind treatment period
    4. Week 26
    5. Week 26
    6. Week 26
    7. Week 26
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Group-sequential
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA59
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Austria
    Belgium
    Brazil
    Bulgaria
    Canada
    China
    Czechia
    Denmark
    Finland
    Germany
    Hungary
    Israel
    Italy
    Korea, Republic of
    Mexico
    Netherlands
    Poland
    Portugal
    Russian Federation
    Slovakia
    South Africa
    Spain
    Sweden
    Switzerland
    Taiwan
    Thailand
    Turkey
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 182
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 98
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 95
    F.4.2.2In the whole clinical trial 280
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After the subject’s study completion, the investigator/delegate will explain to subjects what treatment(s) / medical care is necessary and available according to local regulations. If indicated, the sponsor will provide subjects who completed the study and did not prematurely discontinue study treatment with OL study treatment until access to commercial selexipag is possible in this indication in the subject’s country of residence, according to local regulatory requirements.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-12-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-04-30
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-06-07
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