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    Summary
    EudraCT Number:2021-000720-36
    Sponsor's Protocol Code Number:POP-AID1.0
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-05-06
    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 number2021-000720-36
    A.3Full title of the trial
    oral PHA-022121 for the acute treatment and prophylaxis Of angioedema attacks in Patients with Acquired C1-Inhibitor Deficiency
    Oraal PHA-022121 voor de acute behandeling en profylaxe van angio-oedeem aanvallen in patiënten met verworven C1-esteraseremmer deficiëntie
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Acute treatment and prophylaxis for acquired angioedema
    Aanvals- en onderhoudsbehandeling voor verworven angio-oedeem
    A.3.2Name or abbreviated title of the trial where available
    POP-AID
    A.4.1Sponsor's protocol code numberPOP-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 code1105 AZ
    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 Capsule, soft
    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
    D.3.9.1CAS number 2340111-58-0
    D.3.9.2Current sponsor codePHA-022121
    D.3.9.3Other descriptive name(S)-N-(1-deutero-1-(3-chloro-5-fluoro-2-((2-methyl-4-(1-methyl-1H-1,2,4-triazol-5-yl)quinolin-8-yloxy)methyl)phenyl)ethyl)-2-(difluoromethoxy)acetamide
    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 number10
    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 placeboCapsule, soft
    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
    Acquired angioedema due to C1-inhibitor deficiency
    Verworven angio-oedeem op basis van 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 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 three different single doses of PHA-022121 versus placebo in achieving angioedema symptom relief during acute attacks and the efficacy of prophylactic treatment with PHA-022121 versus placebo in preventing breakthrough angioedema attacks in patients with acquired C1 inhibitor deficiency.
    E.2.2Secondary objectives of the trial
    To further explore the clinical efficacy of PHA-022121 versus placebo with regard to onset of symptom relief, time to complete symptom relief, to evaluate the frequency and timing of rescue medication use, and to evaluate the safety of PHA-022121 versus placebo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    In order to be eligible to participate in this study, a patient must meet all of the following criteria:
    • Provision of signed and dated informed consent form
    • Male or female, aged > 35 at enrollment
    • Diagnosis of AAE-C1-INH based upon all of the following:
    1. Documented clinical history consistent with AAE-C1-INH (subcutaneous or mucosal, nonpruritic swelling without accompanying urticarial 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 4 months, or at least two angioedema attacks in the last 2 months.
    • Reliable access and experience to use 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 enrollment 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 2 weeks after each administration of study drug. In addition, they must agree to not donate sperm during study participation.
    E.4Principal exclusion criteria
    Patients who meet any of the following criteria will be excluded from the study:
    • 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 > 3 drinks/day)
    • History of documented severe hypersensitivity to any medicinal product
    • Participation in any other investigational drug study currently, within the last 30 days or within 5 half-lives of study drug at enrollment (whichever was longer)
    • 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)
    E.5 End points
    E.5.1Primary end point(s)
    • Part 1: 3-symptom composite visual analogue scale (VAS-3) score
    • Part 2: number of investigator-confirmed angioedema attacks
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part 1: VAS-3 is measured from the start of each of the 4 attacks untill 48 hours post-treatment
    Part 2: number of attacks during 8 weeks of treatment with study drug and 8 weeks of treatment with placebo
    E.5.2Secondary end point(s)
    • Part 1: mean symptom complex severity score (MSCS) score
    • Part 1: treatment outcome score (TOS)
    • Part 1: treatment satisfaction questionnaire for medication (TSQM) score
    • Part 1: number of attacks requiring rescue medication
    • Part 1: time to rescue medication use, if applicable
    • Part 2: number of investigator-confirmed moderate or severe angioedema attacks during the treatment period
    • Part 2: number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period
    • Part 2: number and proportion of days with angioedema symptoms during the treatment period
    • Part 2: time to first investigator-confirmed attack (i.e. duration that a patient is attack-free) in the treatment period
    • Part 2: angioedema quality of life (AE-QoL) questionnaire
    • Part 2: treatment satisfaction questionnaire for medication (TSQM) score
    • Part 2: angioedema control test (AECT)
    • Part 2: angioedema activity score (AAS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    End points during part 1 are evaluated from the start of each of the 4 attacks untill 48 hours post-treatment.
    End points during part 2 are evaluated after 8 weeks of treatment with study drug and 8 weeks of treatment with placebo
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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 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 No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    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 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 years0
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    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: 2
    F.1.3Elderly (>=65 years) Yes
    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 state3
    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)
    None
    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 Decision2021-05-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-08-27
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2023-03-16
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