Clinical trial • Phase III • Immunology|Rare Disease

DEUCRICTIBANT for Hereditary angioedema

Phase III trial of DEUCRICTIBANT for Hereditary angioedema. open-label. 73 participants.

Overview

Trial Therapeutic Area
Immunology|Rare Disease
Trial Disease
Hereditary angioedema
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
24-10-2024
First CTIS Authorization Date
04-03-2025

Trial design

open-label Phase III trial in Spain, Austria, Hungary and others.

Open Label
Yes
Target Sample Size
73

Eligibility

Recruits 73 paediatric patients.

Pregnancy Exclusion
Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
Vulnerable Population
Vulnerable population selected. Adolescents are included: "At the time of signing informed consent, male and female participants must be aged ≥12 years. If the participant is an adolescent (ie, aged ≥12 to <18 years or as determined by local law, ≥40 kg), written assent will be obtained from the participant and consent will be obtained from the participant’s parent/legal guardian. A participant who is an adolescent will sign the informed consent form if they reach the age of 18 or as determined by local law during their participation in the study." The Investigator must also consider parent/caregiver involvement and adherence capability for adolescent participants ( Investigator considers that the participant (and parent/caregiver for adolescent participants) is willing and able to adhere to all protocol requirements, including ... data recording into an eDiary).

Inclusion criteria

  • {"criterion_text":"- Provision of written informed consent. At the time of signing informed consent, male and female participants must be aged ≥12 years. If the participant is an adolescent (ie, aged ≥12 to <18 years or as determined by local law, ≥40 kg), written assent will be obtained from the participant and consent will be obtained from the participant’s parent/legal guardian. A participant who is an adolescent will sign the informed consent form if they reach the age of 18 or as determined by local law during their participation in the study\n- Participants who previously participated in HAE studies with deucrictibant on-demand or prophylactic treatment may be eligible to be screened for this study. Participants in Study PHA022121-305 must have completed all study drug treatment and assessments in the double-blind Treatment Period of the previous study\n- Participants who have not previously had their HAE diagnosis confirmed by a central laboratory in a Pharvaris-sponsored study with deucrictibant must meet the following requirements: a.\tDiagnosis of HAE based upon all of the following: •\tDocumented clinical history consistent with HAE (cutaneous or submucosal, nonpruritic swelling without accompanying urticaria) •\tAt least one of the following: 1.\tAge at reported onset of first angioedema symptoms ≤30 years 2.\tFamily history consistent with HAE 3.\tC1q within normal range b.\tDiagnostic testing results to confirm HAE: •\tC1 esterase inhibitor (C1INH) functional level <50% of the normal level must be shown by chromogenic assay performed by the central laboratory as part of the Screening procedures.\n- For Non rollover participants: History of at least 1 attack in the last 3 consecutive months prior to Screening\n- Participant is assessed by the Investigator to have reliable access and ability to use standard of care on-demand treatments to effectively manage acute HAE attacks\n- Investigator considers that the participant (and parent/caregiver for adolescent participants) is willing and able to adhere to all protocol requirements, including the participant being capable of and compliant with data recording into an eDiary\n- Female participants of childbearing potential (or who become of childbearing potential during the study) must agree to the protocol specified pregnancy testing and use an acceptable contraception method defined in the protocol from enrollment until 30 days after the last study drug administration"}

Exclusion criteria

  • {"criterion_text":"- Any diagnosis of angioedema other than HAE\n- Participation in a clinical study with any other investigational drug within the last 30 days or within 5 half-lives of the investigational drug at ICF signature (whichever was longer) or prior gene therapy for any indication at any time\n- Participants who discontinued from previous studies with deucrictibant prophylactic and/or on demand treatment due to safety reasons or compliance issues that, in the opinion of the Investigator, would interfere with the participant’s safety or compliance to participate in the study. Participants who previously received deucrictibant prophylactic and/or on-demand treatment and recently completed a pregnancy may be eligible to participate in this study. \tParticipants may be eligible for this study if the previous study with deucrictibant prophylactic and/or on-demand treatment has been terminated by the Sponsor prior to their completion of the study\n- Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks of Screening\n- For Rollover participants who have completed participation in studies with deucrictibant prophylactic treatment prior to Screening and Non rollover participants: Receiving prophylactic treatment for HAE within the time periods before Screening as indicated below: a.\tLong-term prophylactic therapy for HAE (C1INH, oral kallikrein inhibitors, or anti-fibrinolytics) within 2 weeks prior to Screening b.\tLong-term prophylactic therapy for HAE with attenuated androgens within 4 weeks prior to Screening c.\tLong-term prophylactic monoclonal antibody therapy for HAE (ie, lanadelumab) within 5 half-lives prior to Screening d.\tShort-term prophylaxis for HAE within 7 days prior to Screening\n- Any females who are pregnant, plan to become pregnant, or are currently breast-feeding\n- Abnormal hepatic function (aspartate aminotransferase [AST] >2× upper limit of normal [ULN], alanine aminotransferase [ALT] >2× ULN, or total bilirubin >1.5× ULN or any hepatic impairment via Child-Pugh Scoring System. Participants with Gilbert’s syndrome, defined as isolated increase of total bilirubin ≤3× ULN and AST and ALT within the normal range, are not excluded\n- Moderate to severe renal impairment (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2)\n- Any clinically significant history of angina, myocardial infarction, syncope, stroke, left ventricular hypertrophy or cardiomyopathy, uncontrolled hypertension, bradycardia, or any other clinically significant cardiovascular abnormality within the previous year that, in the opinion of the Investigator, would interfere with the participant's safety or ability to participate in the study\n- History of epilepsy and/or other significant neurological diseases\n- Any clinically significant and uncontrolled gastrointestinal dysfunction (eg, chronic diarrhea, inflammatory bowel disease) which impacts study drug absorption\n- History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse\n- Use of concomitant medications with systemic absorption and foods that are moderate and strong inhibitors of cytochrome P450 (CYP)3A4 such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, and grapefruit juice or strong inducers of CYP3A4 such as carbamazepine, phenytoin, and rifampin within the last 30 days or within 5 half-lives (whichever is longer) of the time of enrollment\n- Known hypersensitivity to deucrictibant or any of the excipients of study drug"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation\n- Clinical laboratory tests\n- Vital signs\n- Electrocardiogram (ECG) parameters","definition_or_measurement_approach":"Treatment-emergent adverse events (TEAEs) will be recorded including SAEs, AESIs, and TEAEs leading to discontinuation. Clinical laboratory tests refer to standard clinical laboratory evaluations. Vital signs measured per protocol (eg, blood pressure, pulse, temperature). ECG parameters assessed by standard ECG recordings."}

Secondary endpoints

  • {"endpoint_text":"- Time-normalized (per 4 weeks) number of Investigator-confirmed HAE attacks during the Treatment Period\n- Time-normalized number of Investigator-confirmed HAE attacks treated with on-demand medication during the Treatment Period\n- Time-normalized number of Investigator-confirmed moderate or severe HAE attacks during Treatment Period\n- Time-normalized number of Investigator-confirmed severe HAE attacks during the Treatment Period\n- Proportion of time without angioedema symptoms during the Treatment Period\n- Angioedema Quality of Life (AE-QoL) questionnaire\n- Patient Global Assessment of Change (PGA-Change)\n- Angioedema Control Test 4-week version (AECT-4wk)\n- Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP)\n- Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9)\n- Deucrictibant plasma concentration pre-dose (Ctrough)","definition_or_measurement_approach":"Many secondary endpoints are time-normalized counts of Investigator-confirmed HAE attacks (per 4 weeks) during Treatment Period; other measures use validated questionnaires (AE-QoL, PGA-Change, AECT-4wk, WPAI-SHP, TSQM-9). Pharmacokinetic endpoint is pre-dose (Ctrough) plasma concentration of deucrictibant."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
73
Recruitment Window Months
46
Consent Approach
Provision of written informed consent is required. "At the time of signing informed consent, male and female participants must be aged ≥12 years. If the participant is an adolescent (ie, aged ≥12 to <18 years or as determined by local law, ≥40 kg), written assent will be obtained from the participant and consent will be obtained from the participant’s parent/legal guardian. A participant who is an adolescent will sign the informed consent form if they reach the age of 18 or as determined by local law during their participation in the study." Subject information and ICF documents are provided for adolescents (12-17) and adults/parents (multiple language versions available in the public documents list).

Methods

  • Digital materials (K2_Recruitment_Materials_DigitalMaterials) - online adverts/website content targeted at patients and HAE communities
  • Website materials (K2_Recruitment_Materials_Website) - trial information pages targeted to prospective participants
  • Posters (K2_Recruitment_Materials_Poster) - clinic/hospital recruitment posters
  • Brochures and fact sheets (K2_Recruitment_Materials_Brochure / K2_Recruitment_Materials_FactSheet) - informational print materials for patients
  • Invite letters (K2_Recruitment_Materials_InviteLetter) - site-specific invitation letters to potential participants
  • Use of third-party communications for recruitment (Praxis Communications LLC listed with role: Recruitment materials)

Geography

Total Number Of Sites
32
Total Number Of Participants
73

Spain

Earliest CTIS Part Ii Submission Date
05-02-2025
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
27
Number Of Sites
3
Number Of Participants
6

Sites

Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Allergy Department
Contact Person Name
Stefan Cimbollek
Site Name
Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca
Department Name
Allergologia
Contact Person Name
Mar Guilarte Clavero
Contact Person Email
mar.guilarte@vallhebron.cat
Site Name
Bellvitge University Hospital
Department Name
Allergology Department
Contact Person Name
Ramón Lleonart Bellfill

Austria

Earliest CTIS Part Ii Submission Date
19-02-2025
Latest Decision Or Authorization Date
10-03-2025
Processing Time Days
19
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Medical University Of Vienna
Department Name
Department of Dermatology
Contact Person Name
Tamar Kinaciyan

Hungary

Earliest CTIS Part Ii Submission Date
10-12-2024
Latest Decision Or Authorization Date
10-03-2025
Processing Time Days
90
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Semmelweis University
Department Name
Department of Internal Medicine
Contact Person Name
Henriette Farkas
Contact Person Email
farkas.henriette@semmelweis.hu

Ireland

Earliest CTIS Part Ii Submission Date
23-01-2025
Latest Decision Or Authorization Date
07-03-2025
Processing Time Days
43
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
St James's Hospital
Department Name
Department of Clinical Immunology
Contact Person Name
Niall Conlon
Contact Person Email
research@stjames.ie

Romania

Earliest CTIS Part Ii Submission Date
10-11-2024
Latest Decision Or Authorization Date
10-03-2025
Processing Time Days
120
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Centrul Clinic Mediquest S.R.L.
Department Name
Alergologie si Imunologie Clinica
Contact Person Name
Noemi-Anna Bara
Contact Person Email
noemi.bara@yahoo.com

Poland

Earliest CTIS Part Ii Submission Date
04-02-2025
Latest Decision Or Authorization Date
09-03-2025
Processing Time Days
33
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
Szpital Uniwersytecki w Krakowie
Department Name
Centrum Alergologii - Poradnia Alergologiczna
Contact Person Name
Marcin Stobiecki
Contact Person Email
marcin.stobiecki@uj.edu.pl

Slovakia

Earliest CTIS Part Ii Submission Date
24-02-2025
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
8
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Univerzitna Nemocnica Martin
Department Name
Ambulancia klinickej imunológie a alergológie
Contact Person Name
Miloš Jeseňák
Contact Person Email
milos.jesenak@uniba.sk

Italy

Earliest CTIS Part Ii Submission Date
12-12-2024
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
82
Number Of Sites
9
Number Of Participants
15

Sites

Site Name
ASST Fatebenefratelli Sacco
Department Name
O.U. General Medicine
Contact Person Name
Antonio Giardo
Site Name
Istituti Clinici Scientifici Maugeri S.p.A.
Department Name
Department of Medicine and Rehabilitation
Contact Person Name
Francesca Perego
Contact Person Email
francesca.perego@icsmaugeri.it
Site Name
Ente Ecclesiastico Ospedale Generale Regionale Miulli
Department Name
Medicine - Division of Nephrology
Contact Person Name
Vincenzo Montinaro
Contact Person Email
v.montinaro@miulli.it
Site Name
Azienda Ospedaliera Universitaria San Giovanni Di Dio E Ruggi d'Aragona
Department Name
Department of Medicine
Contact Person Name
Massimo Triggiani
Contact Person Email
mtriggiani@unisa.it
Site Name
Policlinico San Donato S.p.A.
Department Name
UO Medicina
Contact Person Name
Andrea Zanichelli
Contact Person Email
andrea.zanichelli@unimi.it
Site Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Department Name
Patologia Clinica
Contact Person Name
Pietro Andrea Accardo
Contact Person Email
p.accardo@villasofia.it
Site Name
Azienda Ospedaliera di Padova
Department Name
UOSD Allergologia
Contact Person Name
Mauro Cancian
Contact Person Email
mcancian@unipd.it
Site Name
Azienda Sanitaria Territoriale Di Macerata - Ospedale Civitanova Marche
Department Name
Allergy Unit
Contact Person Name
Maria Guarino
Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
Division of Internal Medicine-Hypertension, Department of Medical Sciences
Contact Person Name
Paola Triggianese
Contact Person Email
paola.triggianese@ptvonline.it

Bulgaria

Earliest CTIS Part Ii Submission Date
04-02-2025
Latest Decision Or Authorization Date
07-03-2025
Processing Time Days
31
Number Of Sites
2
Number Of Participants
10

Sites

Site Name
Alexandrovska University Hospital
Department Name
Clinic of Clinical Allergology
Contact Person Name
Maria Staevska-Kotasheva
Contact Person Email
dr.mariya.staevska@gmail.com
Site Name
Diagnostic - Consultative Center Convex EOOD
Contact Person Name
Anna Valerieva Dimitrova
Contact Person Email
anna.valerieva@gmail.com

Germany

Earliest CTIS Part Ii Submission Date
21-01-2025
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
42
Number Of Sites
6
Number Of Participants
10

Sites

Site Name
Universitaetsklinikum Muenster AöR
Department Name
Bereichsleitung Allergologie und Berufsdermatologie
Contact Person Name
Mathias Sulk
Contact Person Email
mathias.Sulk@ukmuenster.de
Site Name
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
Department Name
Department Oto-Rhino-Layngology
Contact Person Name
Susanne Trainotti
Contact Person Email
susanne.trainotti@tum.de
Site Name
Medizinische Hochschule Hannover
Department Name
Dept. Dermatology and Allergy
Contact Person Name
Bettina Wedi
Contact Person Email
wedi.bettina@mh-hannover.de
Site Name
Goethe University Frankfurt
Department Name
Dept Of Children and Adolescents
Contact Person Name
Emel Aygören-Pürsün
Contact Person Email
aygoeren@em.uni-frankfurt.de
Site Name
HZRM Haemophilie-Zentrum Rhein Main GmbH
Contact Person Name
Inmaculada Martinez Saguer
Contact Person Email
inmaculada.martinez@hzrm.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Institute of Allergology IFA
Contact Person Name
Markus Magerl
Contact Person Email
markus.magerl@charite.de

France

Earliest CTIS Part Ii Submission Date
24-01-2025
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
39
Number Of Sites
6
Number Of Participants
5

Sites

Site Name
Trousseau Hospital
Department Name
Allergology Department
Contact Person Name
Melisande Bourgoin-Heck
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Rhumatologie Pediatrique
Contact Person Name
Heloise Reumaux
Contact Person Email
Heloise.reumaux@chu-lille.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Centre de Ref des Maladies Rare
Contact Person Name
David Launay
Contact Person Email
david.launay@univ-lille.fr
Site Name
Hôpital Archet 1
Department Name
Internal Medicine
Contact Person Name
Pierre-Yves Jeandel
Contact Person Email
jeandel.py@chu-nice.fr
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Department of Internal Medicine
Contact Person Name
Laurence Bouillet
Contact Person Email
lbouillet@chu-grenoble.fr
Site Name
Hopital Saint Antoine
Department Name
Internal Medicine
Contact Person Name
Delphine Gobert
Contact Person Email
delphine.gobert@aphp.fr

Sponsor

Primary sponsor

Full Name
Pharvaris Netherlands B.V.
Organisation Type
Pharmaceutical company
Country Of Registered Address
Netherlands

Contract research organisations

Name
Medpace Reference Laboratories LLC
Responsibilities
Laboratory services (sponsorDuties code 4); C.Saeren@medpace.com
Name
Hangzhou Tigermed Consulting Co. Ltd.
Responsibilities
Site management / regional CRO support (sponsorDuties code 10); firstname.lastname@tigermedgrp.com
Name
AMS Advanced Medical Services Limited
Responsibilities
Operational tasks (sponsorDuties codes 1,2,5); financeLondon@ams-europe.com
Name
Eclinical Solutions LLC
Responsibilities
eClinical services (sponsorDuties code 6); info@eclinicalsol.com
Name
Y-Prime UK Limited
Responsibilities
Randomization/IWRS or data support (sponsorDuties codes 14,3); icarmona@yprime.com

Third parties

  • {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"sponsorDuties codes: [4]; contact email C.Saeren@medpace.com","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"sponsorDuties codes: [6]; contact email info@eclinicalsol.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Praxis Communications LLC","duties_or_roles":"sponsorDuties codes: [15]; value: Recruitment materials; contact email mtutundzic@gopraxis.com","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"AMS Advanced Medical Services Limited","duties_or_roles":"sponsorDuties codes: [1,2,5]","organisation_type":"Pharmaceutical company"}
  • {"country":"China","full_name":"Hangzhou Tigermed Consulting Co. Ltd.","duties_or_roles":"sponsorDuties codes: [10]","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Ardena Bioanalysis B.V.","duties_or_roles":"sponsorDuties codes: [15]; value: PK analysis; contact email daniel.wilffert@ardena.com","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Y-Prime UK Limited","duties_or_roles":"sponsorDuties codes: [14,3]","organisation_type":"Non-Pharmaceutical company"}

Investigational products

Investigational Product Name
Deucrictibant (PHA-022121)
Active Substance
DEUCRICTIBANT
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Starting Dose
40 mg
Dose Levels
40 mg
Maximum Dose
40 mg

Related trials

Other published trials that may interest you.