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    The EU Clinical Trials Register currently displays   43881   clinical trials with a EudraCT protocol, of which   7295   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).

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    Summary
    EudraCT Number:2022-003168-25
    Sponsor's Protocol Code Number:ONCE-AID1.0
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2023-02-28
    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 number2022-003168-25
    A.3Full title of the trial
    Oral ONCE Daily prophylaxis with PHA-022121 in Patients with Acquired C1-Inhibitor Deficiency
    Eenmaal daags oraal PHA-022121 ter profylaxe in patiënten met verworven C1-esteraseremmer deficiëntie
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Prophylactic treatment with PHA-022121 in patients with acquired angioedema
    Onderhoudsbehandeling met PHA-022121 voor patiënten met verworven angio-oedeem
    A.3.2Name or abbreviated title of the trial where available
    ONCE-AID
    A.4.1Sponsor's protocol code numberONCE-AID1.0
    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 SponsorAcademisch Medisch Centrum
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPharvaris
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAcademisch Medisch Centrum
    B.5.2Functional name of contact pointPrincipal Investigator
    B.5.3 Address:
    B.5.3.1Street AddressMeibergdreef 9
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1105AZ
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+310205669111
    B.5.6E-maild.m.cohn@amsterdamumc.nl
    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 No
    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 namePHA-022121
    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 INNPHA-022121 Monohydrate
    D.3.9.2Current sponsor codePHA-022121 Monohydrate
    D.3.9.3Other descriptive nameDeucrictibant
    D.3.9.4EV Substance CodeSUB206489
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Acquired angioedema due to C1-inhibitor deficiency
    Verworven angio-oedeem op basis van een C1-esterase remmer deficiëntie
    E.1.1.1Medical condition in easily understood language
    Acquired angioedema due to C1-inhibitor deficiency
    Verworven angio-oedeem op basis van een C1-esterase remmer deficiëntie
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10081035
    E.1.2Term Acquired C1 inhibitor deficiency
    E.1.2System Organ Class 10040785 - Skin and subcutaneous tissue disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of long-term prophylactic treatment with deucrictibant (PHA-022121) once daily in preventing angioedema attacks in patients with acquired C1 inhibitor deficiency.
    Het primaire doel is het onderzoeken van de effectiviteit van langdurig gebruik van deucrictibant (PHA-022121) met betrekking tot het voorkomen van angio-oedeem aanvallen bij patiënten met verworven C1-esteraseremmer deficiëntie.
    E.2.2Secondary objectives of the trial
    To evaluate the safety of long-term prophylactic use of deucrictibant (PHA-022121) and to further explore the clinical efficacy of deucrictibant (PHA-022121) with regard to quality of life, treatment satisfaction and frequency and timing of on demand medication use.
    Het onderzoeken van de veiligheid van langdurig profylactisch gebruik van deucrictibant (PHA-022121) en het verder onderzoeken van de klinische werkzaamheid van deucrictibant (PHA-022121) met betrekking tot kwaliteit van leven, patiëntentevredenheid ten aanzien van de medicatie en frequentie en timing van gebruik van aanvalsbehandeling.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Provision of signed and dated informed consent form
    • Male or female, aged > 35 at enrolment
    • Diagnosis of AAE-C1-INH based upon all of the following:
    1. Documented clinical history consistent with AAE-C1-INH (subcutaneous or mucosal, nonpruritic swellings without accompanying urticaria and C1-INH activity < 0.63mE/L)
    2. At least one of the following:
    • Age at reported onset of first angioedema symptoms ≥ 40 years AND family history negative for angioedema
    • C1q below lower limit of normal (88 kU/L) AND absence of SERPING1 mutation
    • Serological confirmation of antibodies against C1-INH
    • Documented history of at least three angioedema attacks in the last four months, or at least two angioedema attacks in the last two months. For patients that previously participated in POP-AID part 2, a historical attack-rate of at least three attacks in four months or two attacks in two months previous to the start of POP-AID part 2 is required
    • Reliable access to and experience with using icatibant to effectively manage acute angioedema attacks
    • Female patients of childbearing potential must agree to be abstinent or to use highly effective forms of contraception methods from enrolment through the end of the study. This includes progestin-only oral contraceptive associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD, all types) or intrauterine hormone releasing systems (IUS). A female of childbearing potential whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception.
    • Male patients, including males who are surgically sterile (post vasectomy), who have a female partner of childbearing potential must agree to be sexually abstinent or use a medically acceptable form of barrier contraception for two weeks after each administration of study drug. In addition, they must agree to not donate sperm during study participation.
    - Getekend en gedateerd toestemmingsformulier
    - >35 jaar oud bij screening
    - Diagnose verworven C1-esterase deficiëntie gebaseerd op basis van:
    1. Gedocumenteerde medische voorgeschidenis passend hierbij (niet-jeukende zwellingen van de huid of slijmvliezen zonder urticaria en een C1-esterase activiteit kleiner dan 0.63mE/L.
    2. Tenminste één van de volgende:
    + Leeftijd bij ontstaan van de eerste angio-oedeem symptomen ≥ 40 jaar én negatieve familiegeschiedenis voor angio-oedeem
    + C1q onder de laagste normaalwaarde (88 kU/L) én afwezigheid van SERPING1 mutatie
    + Serologische bevestiging van antilichamen tegen C1-esteraseremmer
    - Gedocumenteerde voorgeschiedenis van tenminste 3 angio-oedeem aanvallen in de laatste 4 maanden, of tenminste 2 aanvallen in de laatste 2 maanden. Voor POP-AID deelnemers geldt een historische aanvalsfrequentie van ten minste 3 aanvallen in de 4 maanden of 2 aanvallen in de 2 maanden voorafgaande aan de start van POP-AID deel 2.
    - Toegang tot en ervaring met icatibant om acute aanvallen te behandelen
    - Indien van toepassing: gebruik van zeer effectieve anticonceptiemethoden
    E.4Principal exclusion criteria
    • Pregnancy or breast-feeding
    • Clinically significant abnormal ECG, most notably a QTcF > 470 ms (for females) or > 450 ms (for males)
    • Any clinically significant history of angina, myocardial infarction, syncope, stroke, left ventricular hypertrophy or cardiomyopathy, or any other cardiovascular abnormality within the previous year
    • Any other systemic disease (e.g., gastrointestinal, renal, respiratory, neurological) or significant disease or disorder that would interfere with the patient’s safety or ability to participate in the study
    • Active infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) or hepatitis C virus (HCV)
    • History of abnormal hepatic function (AST > 2×ULN, ALT > 2×ULN, or total bilirubin > 1.5×ULN)
    • History of abnormal renal function (eGFR CKD-EPI < 60 mL/min/1.73 m2)
    • History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse (self-reported alcoholic intake > three drinks/day)
    • History of documented severe hypersensitivity to any medicinal product
    • Participation in any investigational drug study within five half-lives of study drug at enrolment
    • Regular use of corticosteroids, antihistamines, narcotics, and other pain relief medications for acute angioedema attack treatment
    • Use of concomitant medication that are moderate or potent inhibitors/inducers of CYP3A4 or are metabolized by CYP3A4 and have a narrow therapeutic range, such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit as well as phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids (not for topical use or inhalation)
    - Zwanger of borstvoeding gevend
    - Klinisch significant abnormaal ECG, met name QTc verlenging
    - Klinisch significante voorgeschiedenis van angina pectoris, myocard infarct, syncope, herseninfarct, linkerventrikehypertrofie of cardiomyopathie of een andere cardiovasculaire aandoening in het afgelopen jaar.
    - Systemische aandoeningen (bijvoorbeeld gastrointestinaal, renaal, pulmonaal, neurologisch) of andere aandoening die interfereert met de veiligheid of mogelijkheid van de patiënt om in de studie te participeren.
    - Actieve infectie met HIV of hepatitis B/C
    - Voorgeschiedenis van abnormale leverfunctie (ASAT > 2x ULN, ALAT > 2x ULN of totaal bilirubine > 1.5x ULN)
    - Voorgeschidenis van abnormale nierfunctie (eGFR CKD-EPI < 60 mL/min/1.73 m2)
    - Voorgeschiedenis van alcohol of drugsmisbruik in het afgelopen jaar
    - Voorgeschiedenis van ernstige hypersensitiviteit voor een medicijn
    - Deelname aan een andere interventiestudie met medicatie binnen 5 maal de half-waarde tijd van de studiemedicatie
    - Regelmatig gebruik van corticosteroïden, antihistminica of pijnstillers voor acute angio-oedeemaanvallen
    - Gebruik van medicatie die CYP3A4 remmen/induceren of hierdoor gemetaboliseerd worden
    E.5 End points
    E.5.1Primary end point(s)
    Normalized number of investigator-confirmed angioedema attacks
    Het aantal angio-edeem aanvallen (bevestigd door de onderzoeker)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Normalized number of investigator-confirmed angioedema attacks per four weeks of exposure compared to baseline (deucrictibant (PHA-022121) naive participants) or before treatment with deucrictibant (PHA-022121) (previous POP-AID part 2 participants)
    Het aantal angio-edeem aanvallen (bevestigd door de onderzoeker) per 28 dagen behandeling in vergelijking met de historische aanvalsfrequentie.
    E.5.2Secondary end point(s)
    • Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period
    • Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period
    • Duration in days of the longest attack free interval
    • Change from baseline (deucrictibant (PHA-022121) naïve patients) or change from before treatment with deucrictibant (PHA-022121) (previous POP-AID part 2 participants) in the Angioedema Control Test (AECT)
    • Change from baseline (deucrictibant (PHA-022121) naïve patients) or change from before first prophylactic treatment with deucrictibant (PHA-022121) (previous POP-AID part 2 participants) in the Angioedema Quality of Life (AE-QoL) after completion of the treatment period
    • AE-QoL-score at 1, 3, 6, 9 and 12 months
    • Treatment satisfaction questionnaire for Medication (TSQM) at 1, 3, 6, 9 and 12 months
    • Occurrence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (AEs), and treatment-emergent serious adverse events (TESAEs), including clinically significant changes in clinical laboratory tests, vital signs or ECG reported as AE
    Effectiviteit:
    - Het aantal matige of ernstige angio-oedeem aanvallen gedurende de behandelperiode
    - Het aantal angio-oedeem aanvallen die acute aanvalsmedicatie behoeven
    - De duur van de langste aanvalsvrije periode
    - Angioedema Control Test (AECT) score tov vóór behandeling
    - Angioedema Quality of Life (AE-QoL) score tov voor behandeling
    - Angioedema Quality of Life (AE-QoL) score na 1, 3, 6, 9 en 12 maanden behandeling
    - Treatment satisfaction questionnaire for Medication (TSQM) score na 1, 3, 6, 9 en 12 maanden behandeling

    Veilighed:
    - Het optreden van ongewenste voorvallen tijdens de behandeling
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary endpoints are evaluated after 12 months of treatment.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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 years1
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 4
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 1
    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 state5
    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 completion of participation in the clinical trial, the IMP will be available for participants with a good response on a compassionate use basis until registration of the product, in consultation with their physician.
    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 Decision2023-02-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-02-17
    P. End of Trial
    P.End of Trial StatusOngoing
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