Clinical trial • Phase III • Haematology

SEBETRALSTAT for Hereditary angioedema (Type I or II)

Phase III trial of SEBETRALSTAT for Hereditary angioedema (Type I or II). open-label. 75 participants.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Hereditary angioedema (Type I or II)
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
23-11-2023
First CTIS Authorization Date
26-02-2024

Trial design

open-label Phase III trial in Austria, Italy, Portugal and others.

Open Label
Yes
Target Sample Size
75

Eligibility

Recruits 75 paediatric patients.

Pregnancy Exclusion
Any pregnant or breastfeeding patient.
Vulnerable Population
Includes adolescents aged 12–17 (vulnerable population). The patient must provide signed informed consent or assent when applicable; a parent or legally authorised representative (LAR) must also provide signed informed consent when required. Country-specific assent and parental ICF documents are provided (separate adolescent assent forms and parental ICFs listed in the documentation). The Investigator assesses the patient's ability to consent/assent and to complete study procedures (e.g., eDiary).

Inclusion criteria

  • {"criterion_text":"- Patients may roll over from KVD900-301.\n- Patient provides signed informed consent or assent (when applicable). A parent or LAR must also provide signed informed consent when required.\n- Confirmed diagnosis of HAE type I or II at any time in the medical history\n- Patient has had at least 2 documented HAE attacks within 3 months prior to the Enrollment Visit\n- If a patient is receiving long-term prophylactic treatment with one of the protocol-allowed therapies, they must have been on a stable dose and regimen for at least 3 months prior to the Enrollment Visit\n- Male or female patients 12 years of age and older.\n- Patients must meet the contraception requirements.\n- Patients must be able to swallow trial tablets whole.\n- Patients, as assessed by the Investigator, must be able to appropriately receive and store IMP, and be able to read, understand, and complete the eDiary.\n- Investigator believes that the patient is willing and able to adhere to all protocol requirements."}

Exclusion criteria

  • {"criterion_text":"- Discontinued from the KVD900-301 trial for reasons of non-compliance, withdrawal of consent, or safety.\n- History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.\n- Known hypersensitivity to KVD900 or to any of the excipients.\n- Participation in any gene therapy treatment or trial for HAE.\n- Participation in any interventional investigational clinical trial, including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to the Enrollment Visit.\n- Any pregnant or breastfeeding patient.\n- Presence of any safety concerns that would preclude participation in the open-label trial as determined by the investigator.\n- Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor deficiency, HAE with normal C1-INH (previously known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria.\n- A clinically significant history of poor response to bradykinin receptor 2 (BR2) blocker, C1-INH therapy, or plasma kallikrein inhibitor therapy for the management of HAE, in the opinion of the Investigator.\n- Use of attenuated androgens (e.g., stanozolol, danazol, oxandrolone, methyltestosterone, testosterone), or anti-fibrinolytics (e.g., tranexamic acid) within 28 days prior to the Enrollment Visit.\n- Use of ACE inhibitors within 7 days prior to the Enrollment Visit.\n- Any estrogen-containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) within 7 days prior to the Enrollment Visit.\n- Inadequate organ function, including but not limited to: a) Alanine aminotransferase (ALT) >2x ULN b) Aspartate aminotransferase (AST) >2x ULN c) Bilirubin direct >1.25x ULN d) INR >1.2 e) Clinically significant hepatic impairment defined as a Child-Pugh B or C\n- Any clinically significant comorbidity or systemic dysfunction, which in the opinion of the Investigator, would jeopardize the safety of the patient by participating in the trial."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Frequencies and percentages of patients with AEs, AEs within 2 days of IMP administration, serious AEs, and AEs causing premature discontinuation","definition_or_measurement_approach":"Measured as frequencies and percentages of patients with adverse events (including AEs within 2 days of IMP administration), serious adverse events, and AEs causing premature discontinuation (per scheduled assessments and safety reporting)."}
  • {"endpoint_text":"- Number and percentage of patients with normal or abnormal laboratory results at each scheduled visit","definition_or_measurement_approach":"Measured as counts and percentages of patients with normal versus abnormal laboratory results at each scheduled visit."}
  • {"endpoint_text":"- Number and percentage of patients with normal or abnormal vital sign results at each scheduled visit","definition_or_measurement_approach":"Measured as counts and percentages of patients with normal versus abnormal vital sign measurements at each scheduled visit."}

Secondary endpoints

  • {"endpoint_text":"- PGI-C: time to beginning of symptom relief defined as at least '' a little better'' (2 time points in a row) within 12 hours of initial dose of IMP administration.","definition_or_measurement_approach":"Patient Global Impression of Change (PGI-C): time from initial IMP dose to first occurrence of at least 'a little better' on two consecutive time points within 12 hours."}
  • {"endpoint_text":"- PGI-S: time to first incidence of 2 time points in a row decrease from baseline within 12 hours of initial dose of IMP administration.","definition_or_measurement_approach":"Patient Global Impression of Severity (PGI-S): time from initial IMP dose to first occurrence of a decrease from baseline on two consecutive time points within 12 hours."}
  • {"endpoint_text":"- PGI-S: time to HAE attack resolution defined as ''none'' within 24 hours of initial dose of IMP administration.","definition_or_measurement_approach":"PGI-S: time from initial IMP dose to resolution of HAE attack (PGI-S = 'none') within 24 hours."}

Recruitment

Registry Or Advocacy Recruitment
True: site and patient advocacy contact list referenced (no specific organisations named in the public documents)
Digital Remote Recruitment
True: use of email communications (patient concierge emails, Scout email communications), digital eDiary for patients, and electronic communications/materials (flip-charts, appointment reminder emails) referenced in country documents
Planned Sample Size
75
Recruitment Window Months
44
Consent Approach
Patients provide signed informed consent; adolescents (12–17 years) provide assent where applicable and a parent or legally authorised representative (LAR) must also sign parental ICFs when required. Country- and age-specific assent and parental ICF documents are provided (examples in the dossier: assent forms and parental ICFs for 12–13 and 14–17 years; main ICFs and parental ICFs available in multiple country languages).

Methods

  • Site and patient advocacy contact lists (document: Site_and_Patient_Advocacy_Contact_List_for_ICF_Public)
  • Country-specific recruitment arrangements documents (K1/Recruiment-Arrangements PDFs per country)
  • GP letter (e.g. K2_KVD900-302_GP_Letter_HU for Hungary)
  • Patient Concierge communications including welcome and unable-to-reach emails (Hungary documents)
  • Appointment reminder cards and patient cards (Hungary documents)
  • Scout email communications and ScoutPass reloadable voucher materials (Hungary documents)
  • IA Flip-Chart recruitment materials (Spain and PK-substudy flip-charts listed)
  • Digital communications via email and site contact (many country-specific documents reference email contact details)

Geography

Total Number Of Sites
26
Total Number Of Participants
75

Austria

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
03-03-2025
Processing Time Days
446
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Medical University Of Vienna
Department Name
Department of Dermatology
Principal Investigator Name
Tamar Kinaciyan
Principal Investigator Email
tamar.kinaciyan@meduniwien.ac.at
Contact Person Name
Tamar Kinaciyan

Italy

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
28-02-2025
Processing Time Days
443
Number Of Sites
4
Number Of Participants
8

Sites

Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
Dipartimento di Scienze Mediche, UOC Reumatologia
Principal Investigator Name
Paola Triggianese
Principal Investigator Email
paola.triggianese@ptvonline.it
Contact Person Name
Paola Triggianese
Contact Person Email
paola.triggianese@ptvonline.it
Site Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Department Name
UOC di Patologia Clinica – Centro Angioedema
Principal Investigator Name
Francesco Arcoleo
Principal Investigator Email
farcoleo@villasofia.it
Contact Person Name
Francesco Arcoleo
Contact Person Email
farcoleo@villasofia.it
Site Name
Azienda Ospedale-Universita Padova
Department Name
Clinica Medica 1 Dipartimento di Medicina dei Sistemi UOSD Allergologia
Principal Investigator Name
Mauro Cancian
Principal Investigator Email
mcancian@unipd.it
Contact Person Name
Mauro Cancian
Contact Person Email
mcancian@unipd.it
Site Name
IRCCS Policlinico San Donato
Department Name
U.O. di Medicina Interna
Principal Investigator Name
Andrea Zanichelli
Principal Investigator Email
andrea.zanichelli@unimi.it
Contact Person Name
Andrea Zanichelli
Contact Person Email
andrea.zanichelli@unimi.it

Portugal

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
26-02-2025
Processing Time Days
442
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Unidade Local de Saude de Sao Joao E.P.E.
Department Name
Immunoallergology Service
Principal Investigator Name
Eunice Dias de Castro
Principal Investigator Email
eunicediascastro@gmail.com
Contact Person Name
Eunice Dias de Castro
Contact Person Email
eunicediascastro@gmail.com

Spain

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
27-02-2025
Processing Time Days
442
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
Hospital Universitari Vall D Hebron
Department Name
Servicio de Alergia
Principal Investigator Name
Mar Guilarte Clavero
Principal Investigator Email
mguilarte@vhebron.net
Contact Person Name
Mar Guilarte Clavero
Contact Person Email
mguilarte@vhebron.net
Site Name
Bellvitge University Hospital
Department Name
Servicio de Alergia
Principal Investigator Name
Ramón Lleonart Bellfill
Principal Investigator Email
rlleonart@gmail.com
Contact Person Name
Ramón Lleonart Bellfill
Contact Person Email
rlleonart@gmail.com
Site Name
Hospital Universitario La Paz
Department Name
Servicio de Alergia
Principal Investigator Name
Teresa Caballero Molina
Principal Investigator Email
tercaballero@gmail.com
Contact Person Name
Teresa Caballero Molina
Contact Person Email
tercaballero@gmail.com

Romania

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
03-03-2025
Processing Time Days
446
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Centrul Clinic Mediquest S.R.L.
Department Name
Allergology and clinical immunology
Principal Investigator Name
Noemi Bara
Principal Investigator Email
noemi.bara@yahoo.com
Contact Person Name
Noemi Bara
Contact Person Email
noemi.bara@yahoo.com

Hungary

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
27-02-2025
Processing Time Days
442
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Semmelweis University
Department Name
Belgyogyaszati es Hematologiai Klinika
Principal Investigator Name
Henriette FARKAS
Principal Investigator Email
farkas.henriette@med.semmelweis-univ.hu
Contact Person Name
Henriette FARKAS

Bulgaria

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
447
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Alexandrovska University Hospital
Department Name
Allergology clinic
Principal Investigator Name
Maria Staevska
Principal Investigator Email
mari66sta@gmail.com
Contact Person Name
Maria Staevska
Contact Person Email
mari66sta@gmail.com

Netherlands

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
05-03-2025
Processing Time Days
448
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Academisch Medisch Centrum
Principal Investigator Name
Danny Michael Cohn
Principal Investigator Email
HAE@amsterdamumc.nl
Contact Person Name
Danny Michael Cohn
Contact Person Email
HAE@amsterdamumc.nl

Greece

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
447
Number Of Sites
2
Number Of Participants
8

Sites

Site Name
Athens Naval Hospital
Department Name
Allergiology Department
Principal Investigator Name
Fotios Psarros
Principal Investigator Email
psarros@allergy.gr
Contact Person Name
Fotios Psarros
Contact Person Email
psarros@allergy.gr
Site Name
Laiko General Hospital Of Athens
Department Name
Allergiology Department
Principal Investigator Name
Nikolaos Mikos
Principal Investigator Email
mikosnikos@gmail.com
Contact Person Name
Nikolaos Mikos
Contact Person Email
mikosnikos@gmail.com

Poland

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
02-03-2025
Processing Time Days
445
Number Of Sites
2
Number Of Participants
8

Sites

Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
Department Name
Ambulatoria Uniwersyteckie Zespół Poradni Specjalistycznych SU Centrum Alergologii
Principal Investigator Name
Marcin Stobiecki
Principal Investigator Email
centrumalergologii@su.krakow.pl
Contact Person Name
Marcin Stobiecki
Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi
Department Name
Klinika Immunologii i Alergii
Principal Investigator Name
Marcin Maciej Kurowski
Principal Investigator Email
marcin.kurowski@umed.lodz.pl
Contact Person Name
Marcin Maciej Kurowski
Contact Person Email
marcin.kurowski@umed.lodz.pl

Slovakia

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
27-02-2025
Processing Time Days
441
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Univerzitna Nemocnica Martin
Department Name
Klinika detí a dorastu
Principal Investigator Name
Miloš Jeseňák
Principal Investigator Email
jesenak@gmail.com
Contact Person Name
Miloš Jeseňák
Contact Person Email
jesenak@gmail.com

France

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
08-08-2025
Processing Time Days
604
Number Of Sites
4
Number Of Participants
10

Sites

Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Service de Médecine Interne
Principal Investigator Name
Laurence BOUILLET
Principal Investigator Email
lbouillet@chu-grenoble.fr
Contact Person Name
Laurence BOUILLET
Contact Person Email
lbouillet@chu-grenoble.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Unité Pédiatrique de Rhumatologie
Principal Investigator Name
Héloïse REUMAUX
Principal Investigator Email
heloise.reumaux@chu-lille.fr
Contact Person Name
Héloïse REUMAUX
Contact Person Email
heloise.reumaux@chu-lille.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service de Médecine Interne Bâtiment de l'Horloge
Principal Investigator Name
Olivier Fain
Principal Investigator Email
olivier.fain@aphp.fr
Contact Person Name
Olivier Fain
Contact Person Email
olivier.fain@aphp.fr
Site Name
Centre Hospitalier Universitaire De Lille (second site)
Department Name
Service De Médecine Interne
Principal Investigator Name
David Launay
Principal Investigator Email
david.launay@univ-lille.fr
Contact Person Name
David Launay
Contact Person Email
david.launay@univ-lille.fr

Germany

Earliest CTIS Part Ii Submission Date
13-12-2023
Latest Decision Or Authorization Date
06-02-2026
Processing Time Days
786
Number Of Sites
4
Number Of Participants
12

Sites

Site Name
Universitaetsmedizin Der Johannes Gutenberg-Universitaet Mainz
Department Name
Haut-und Poliklinik Abteilung für Dermatologie und Allergologie
Principal Investigator Name
Petra Staubach-Renz
Principal Investigator Email
petra.staubach@unimedizin-mainz.de
Contact Person Name
Petra Staubach-Renz
Site Name
HZRM Haemophilie-Zentrum Rhein Main GmbH
Department Name
Diagnostik, Therapie und Erforschung von Gerinnungsstörungen, Immundefekten und HAE
Principal Investigator Name
Carmen Escuriola Ettingshausen
Principal Investigator Email
inmaculada.martinez@hzrm.de
Contact Person Name
Carmen Escuriola Ettingshausen
Contact Person Email
inmaculada.martinez@hzrm.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Institute of Allergology (IFA)
Principal Investigator Name
Markus Magerl
Principal Investigator Email
markus.magerl@charite.de
Contact Person Name
Markus Magerl
Contact Person Email
markus.magerl@charite.de
Site Name
Universitaetsklinikum Frankfurt AöR
Department Name
Klinik für Kinder- und Jugendmeizin
Principal Investigator Name
Emel Aygören-Pürsün
Principal Investigator Email
emel.aygoeren@kgu.de
Contact Person Name
Emel Aygören-Pürsün
Contact Person Email
emel.aygoeren@kgu.de

Sponsor

Primary sponsor

Full Name
Kalvista Pharmaceuticals Limited
Organisation Type
Pharmaceutical company
Country Of Registered Address
United Kingdom

Contract research organisations

Name
Ppd Inc.
Responsibilities
Clinical operations, monitoring, data management and other operational sponsor duties; CSR Writing and multiple listed responsibilities
Name
Medidata Solutions International Limited
Responsibilities
IVRS / randomisation (IVRS30 – treatment randomisation)
Name
PPD Global Central Labs / PPD Global Clinical Labs
Responsibilities
Laboratory services (central lab activities)
Name
Arriello s.r.o.
Responsibilities
Aggregate report and line listing submission activities; safety reporting contact (email kalvista.safety@arriello.com)
Name
Mayo Collaborative Services LLC
Responsibilities
C1-esterase inhibitor activity and antigen testing
Name
York Bioanalytical Solutions Limited
Responsibilities
Bioanalytical testing services

Third parties

  • {"country":"Czechia","full_name":"Arriello s.r.o.","duties_or_roles":"Aggregate report and line listing submission activities; (additional sponsor duties codes present)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"C1-esterase inhibitor activity (functional level) and C1-esterase inhibitor protein (antigen)","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"IVRS30 – treatment randomisation; (additional sponsor duty code present)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"Multiple sponsor duties including CSR Writing and other study operational responsibilities (codes listed in dossier)","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Central laboratory services (sponsor duty code 4)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Global Clinical Labs","duties_or_roles":"Central laboratory services (sponsor duty code 4)","organisation_type":"Industry (lab)"}
  • {"country":"United Kingdom","full_name":"York Bioanalytical Solutions Limited","duties_or_roles":"Bioanalytical laboratory services (sponsor duty code 4)","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
KVD900 (ORODISPERSIBLE TABLET)
Active Substance
SEBETRALSTAT
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised
Orphan Designation
Yes
Maximum Dose
900 mg
Investigational Product Name
KVD900 (FILM-COATED TABLET)
Active Substance
SEBETRALSTAT
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised
Orphan Designation
Yes
Maximum Dose
1800 mg

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