Clinical trial • Phase II • Cardiology

NINERAFAXSTAT TRIHYDROCHLORIDE MONOHYDRATE for Non-obstructive hypertrophic cardiomyopathy

Phase II trial of NINERAFAXSTAT TRIHYDROCHLORIDE MONOHYDRATE for Non-obstructive hypertrophic cardiomyopathy.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Non-obstructive hypertrophic cardiomyopathy
Trial Stage
Phase II
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
06-08-2025
First CTIS Authorization Date
20-11-2025

Trial design

Randomised, placebo: 'tablet, identical in appearance to ninerafaxstat tablets' (matching placebo). active comparator: ninerafaxstat 200 mg mr bid (modified-release tablet, oral).-controlled Phase II trial in Austria, France, Poland and others.

Randomised
Yes
Comparator
Placebo: 'Tablet, identical in appearance to ninerafaxstat tablets' (matching placebo). Active comparator: Ninerafaxstat 200 mg MR BID (modified-release tablet, oral).
Target Sample Size
80
Trial Duration For Participant
365

Stratification factors

  • CPET exercise modality
  • KCCQ-CSS score
  • BMI

Eligibility

Recruits 80 isVulnerablePopulationSelected is true. Participants must be able to comprehend and sign an informed consent form: "Able to comprehend and willing to sign an informed consent form (ICF), and willing to comply with all trial procedures and restrictions for the duration specified in the Schedule of Events. Understands the risks involved." Pregnant or breastfeeding women are excluded and specific pregnancy-related ICFs/documents are provided..

Pregnancy Exclusion
6. Pregnancy and Lactation: • Pregnant or breastfeeding women. • Women of childbearing potential not willing to use effective contraception during the study and for a specified period after the last dose.
Vulnerable Population
isVulnerablePopulationSelected is true. Participants must be able to comprehend and sign an informed consent form: "Able to comprehend and willing to sign an informed consent form (ICF), and willing to comply with all trial procedures and restrictions for the duration specified in the Schedule of Events. Understands the risks involved." Pregnant or breastfeeding women are excluded and specific pregnancy-related ICFs/documents are provided.

Inclusion criteria

  • {"criterion_text":"- All inclusion criteria can be found in the protocol (Section 5.1). 1. Informed Consent: Able to comprehend and willing to sign an informed consent form (ICF), and willing to comply with all trial procedures and restrictions for the duration specified in the Schedule of Events. Understands the risks involved.\n- 2. Age: Individual ≥18 years of age at the time of signing informed consent.\n- 3. Echocardiography: Has adequate acoustic windows for echocardiography.\n- 4. Clinical Diagnosis: Has a clinical diagnosis of hypertrophic cardiomyopathy (HCM) consistent with current American College of Cardiology/American Heart Association and European Society of Cardiology Guideline definition, with unexplained left ventricular hypertrophy (LVH) in the absence of other cardiac or systemic diseases that can produce the magnitude of hypertrophy observed."}

Exclusion criteria

  • {"criterion_text":"- All exclusion criteria can be found in the protocol (Section 5.2). 1. Informed Consent: Inability or unwillingness to provide informed consent or comply with trial procedures.\n- 2. Cardiovascular Conditions: •\tHistory of obstructive hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract (LVOT) gradient ≥30 mmHg at rest or with provocation. •\tHistory of major adverse cardiovascular events (MACE) within 6 months prior to screening, including myocardial infarction, stroke, or cardiac surgery.\n- 3. Medical Conditions: •\tSignificant comorbidities that may impact the ability to complete the trial or the interpretation of results, such as uncontrolled diabetes, severe renal impairment, or active infection. •\tKnown history of hepatitis B or C infection, or HIV infection.\n- 4. Medications: •\tUse of disallowed medications that may interfere with the trial, such as other investigational drugs within 30 days prior to screening. •\tRequirement for treatment with drugs that may affect the study outcomes, such as certain antiarrhythmic or antihypertensive medications.\n- 5. Substance Abuse: History of alcohol or substance abuse within the past year.\n- 6. Pregnancy and Lactation: •\tPregnant or breastfeeding women. •\tWomen of childbearing potential not willing to use effective contraception during the study and for a specified period after the last dose.\n- 7. Other Exclusions: •\tParticipation in another clinical trial within 30 days prior to screening. •\tAny condition that, in the opinion of the investigator, would make participation in the trial unsafe or otherwise not in the best interest of the participant."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS).","definition_or_measurement_approach":"Change from baseline to Week 12 in the KCCQ Clinical Summary Score (KCCQ-CSS); measured by KCCQ score at baseline and at Week 12."}

Secondary endpoints

  • {"endpoint_text":"- 1. Change in ventilatory efficiency (VE/VCO2 slope) during CPET from baseline to Week 12","definition_or_measurement_approach":"Change from baseline to Week 12 in VE/VCO2 slope measured during cardiopulmonary exercise testing (CPET)."}
  • {"endpoint_text":"- 2. Change from baseline to Week 12 in the KCCQ-TSS","definition_or_measurement_approach":"Change from baseline to Week 12 in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)."}
  • {"endpoint_text":"- 3. Change from baseline to Week 12 in the KCCQ-PLS","definition_or_measurement_approach":"Change from baseline to Week 12 in the KCCQ Physical Limitation Score (KCCQ-PLS)."}
  • {"endpoint_text":"- 4. Change from baseline to Week 12 in the KCCQ-OSS","definition_or_measurement_approach":"Change from baseline to Week 12 in the KCCQ Overall Summary Score (KCCQ-OSS)."}
  • {"endpoint_text":"- 5. Change in exercise duration during CPET from baseline to Week 12","definition_or_measurement_approach":"Change from baseline to Week 12 in exercise duration during CPET (timed CPET performance)."}

Recruitment

Registry Or Advocacy Recruitment
True, Fondazione Toscana Gabriele Monasterio (listed as a patient organisation/association involved as third party) and a 'Site-Patient-advocacy-Contact-List' document are present.
Planned Sample Size
80
Recruitment Window Months
10
Consent Approach
Participants must provide written informed consent themselves (inclusion criterion: 'Able to comprehend and willing to sign an informed consent form (ICF)...'). Only adults ≥18 years may enroll (no assent). Multiple language ICFs and related documents are provided (examples include English, German, French, Spanish, Portuguese, Polish, Italian, Dutch). Pregnancy-related ICFs are available where applicable; pregnancy and lactation are exclusion criteria.

Methods

  • Country-specific recruitment arrangements packages (documents titled 'Recruitment arrangements' for multiple countries) - materials include fact sheets, recruitment brochures, flipcharts, appointment cards, patient letters and GP/doctor letters.
  • Direct site-based recruitment using patient letters and doctor-to-doctor/GP letters (country-specific documents present for DE, FR, PL, IT, ES, PT, NL, BE, AT).
  • Printed materials and appointment cards (country-specific) to schedule screening/visits.
  • Core laboratory outreach (e.g. cardiopulmonary exercise testing and echocardiography core labs named in third-party roles) supporting site activities.

Geography

Total Number Of Sites
40
Total Number Of Participants
130

Austria

Earliest CTIS Part Ii Submission Date
02-10-2025
Latest Decision Or Authorization Date
23-11-2025
Processing Time Days
52
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Medical University Of Graz
Department Name
Klinische Abteilung für Kardiologie
Principal Investigator Name
Nicolas Dominik Verheyen
Principal Investigator Email
nicolas.verheyen@medunigraz.at
Contact Person Name
Nicolas Dominik Verheyen
Contact Person Email
nicolas.verheyen@medunigraz.at

France

Earliest CTIS Part Ii Submission Date
03-11-2025
Latest Decision Or Authorization Date
21-11-2025
Processing Time Days
18
Number Of Sites
3
Number Of Participants
15

Sites

Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Cardiology
Principal Investigator Name
Nicolas PIRIOU
Principal Investigator Email
nicolas.piriou@chu-nantes.fr
Contact Person Name
Nicolas PIRIOU
Contact Person Email
nicolas.piriou@chu-nantes.fr
Site Name
Assistance Publique Hopitaux De Paris
Principal Investigator Name
Albert HAGEGE
Principal Investigator Email
albert.hagege@aphp.fr
Contact Person Name
Albert HAGEGE
Contact Person Email
albert.hagege@aphp.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Cardiology
Principal Investigator Name
François ROUBILLE
Principal Investigator Email
f-roubille@chu-montpellier.fr
Contact Person Name
François ROUBILLE
Contact Person Email
f-roubille@chu-montpellier.fr

Poland

Earliest CTIS Part Ii Submission Date
18-11-2025
Latest Decision Or Authorization Date
30-11-2025
Processing Time Days
12
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
4 Wojskowy Szpital Kliniczny Z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej We Wroclaw
Department Name
Ośrodek Chorób Serca, Klinika Kardiologii, Oddział Niewydolności Serca
Principal Investigator Name
Bartosz Krakowiak
Principal Investigator Email
bartek.krakowiak@gmail.com
Contact Person Name
Bartosz Krakowiak
Contact Person Email
bartek.krakowiak@gmail.com
Site Name
Kardio Brynow Sp. z o.o.
Principal Investigator Name
Wojciech Wojakowski
Principal Investigator Email
wojtek.wojakowski@gmail.com
Contact Person Name
Wojciech Wojakowski
Contact Person Email
wojtek.wojakowski@gmail.com
Site Name
Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji
Department Name
Klinika Kardiologii
Principal Investigator Name
Agnieszka Pawlak
Principal Investigator Email
agnieszka.pawlak@pimmswia.gov.pl
Contact Person Name
Agnieszka Pawlak

Netherlands

Earliest CTIS Part Ii Submission Date
18-11-2025
Latest Decision Or Authorization Date
20-11-2025
Processing Time Days
2
Number Of Sites
4
Number Of Participants
12

Sites

Site Name
Amsterdam UMC Research B.V.
Department Name
Cardiology
Principal Investigator Name
Ahmad Amin
Principal Investigator Email
a.s.amin@amsterdamumc.nl
Contact Person Name
Ahmad Amin
Contact Person Email
a.s.amin@amsterdamumc.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Cardiology
Principal Investigator Name
Michelle Michels
Principal Investigator Email
m.michels@erasmusmc.nl
Contact Person Name
Michelle Michels
Contact Person Email
m.michels@erasmusmc.nl
Site Name
Radboud universitair medisch centrum Stichting
Department Name
Cardiology
Principal Investigator Name
Robin Nijveldt
Principal Investigator Email
onderzoek.cardio@radboudumc.nl
Contact Person Name
Robin Nijveldt
Contact Person Email
onderzoek.cardio@radboudumc.nl
Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Cardiology
Principal Investigator Name
Nina Ajmone Marsan
Principal Investigator Email
N.Ajmone@lumc.nl
Contact Person Name
Nina Ajmone Marsan
Contact Person Email
N.Ajmone@lumc.nl

Belgium

Earliest CTIS Part Ii Submission Date
27-08-2025
Latest Decision Or Authorization Date
20-11-2025
Processing Time Days
85
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Universitair Ziekenhuis Antwerpen
Department Name
Cardiology
Principal Investigator Name
Emeline Van Craenenbroeck
Principal Investigator Email
emeline.vancraenenbroeck@uantwerpen.be
Contact Person Name
Emeline Van Craenenbroeck

Germany

Earliest CTIS Part Ii Submission Date
03-11-2025
Latest Decision Or Authorization Date
20-11-2025
Processing Time Days
17
Number Of Sites
4
Number Of Participants
12

Sites

Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Klinik für Kardiologie, Angiologie und Pneumologie
Principal Investigator Name
Benjamin Meder
Principal Investigator Email
Benjamin.Meder@med.uni-heidelberg.de
Contact Person Name
Benjamin Meder
Site Name
Universitaetsmedizin Goettingen
Department Name
Klinik für Kardiologie und Pneumologie
Principal Investigator Name
Soeren Brandenburg
Principal Investigator Email
soeren.brandenburg@med.uni-goettingen.de
Contact Person Name
Soeren Brandenburg
Site Name
Herz Und Diabeteszentrum NRW Bad Oeynhausen Universitaetsklinik Der Ruhr-Universitaet Bochum
Department Name
Klinik für Allgemeine und Interventionelle Kardiologie/Angiologie
Principal Investigator Name
Smita Scholtz
Principal Investigator Email
sscholtz@hdz-nrw.de
Contact Person Name
Smita Scholtz
Contact Person Email
sscholtz@hdz-nrw.de
Site Name
Universitaetsklinikum Jena KöR
Department Name
Klinik für Innere Medizin I
Principal Investigator Name
Julian Westphal
Principal Investigator Email
Julian.Westphal@med.uni-jena.de
Contact Person Name
Julian Westphal

Portugal

Earliest CTIS Part Ii Submission Date
08-10-2025
Latest Decision Or Authorization Date
21-11-2025
Processing Time Days
44
Number Of Sites
3
Number Of Participants
12

Sites

Site Name
Unidade Local De Saude Do Alto Ave E.P.E.
Department Name
Cardiology Department
Principal Investigator Name
Olga Azevedo
Principal Investigator Email
olgazevedo@yahoo.com.br
Contact Person Name
Olga Azevedo
Contact Person Email
olgazevedo@yahoo.com.br
Site Name
Hospital Da Luz S.A.
Department Name
Cardiology Department
Principal Investigator Name
Alexandra Toste
Principal Investigator Email
atoste@hospitaldaluz.pt
Contact Person Name
Alexandra Toste
Contact Person Email
atoste@hospitaldaluz.pt
Site Name
Unidade Local De Saude De Sao Jose E.P.E.
Department Name
Cardiology Department
Principal Investigator Name
Sílvia Aguiar Rosa
Principal Investigator Email
silvia.rosa@ulssjose.min-saude.pt
Contact Person Name
Sílvia Aguiar Rosa

Spain

Earliest CTIS Part Ii Submission Date
23-10-2025
Latest Decision Or Authorization Date
05-12-2025
Processing Time Days
43
Number Of Sites
15
Number Of Participants
45

Sites

Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Cardiology
Principal Investigator Name
Roberto Barriales Villa
Principal Investigator Email
Roberto.barriales.villa@sergas.es
Contact Person Name
Roberto Barriales Villa
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Cardiology
Principal Investigator Name
Marta De Antonio Ferrer
Principal Investigator Email
mantoniof@santpau.cat
Contact Person Name
Marta De Antonio Ferrer
Contact Person Email
mantoniof@santpau.cat
Site Name
Bellvitge University Hospital
Department Name
Cardiology
Principal Investigator Name
Carles Diez Lopez
Principal Investigator Email
soceldiez@gmail.com
Contact Person Name
Carles Diez Lopez
Contact Person Email
soceldiez@gmail.com
Site Name
Hospital Alvaro Cunqueiro
Department Name
Cardiology
Principal Investigator Name
Rafael Jose Cobas Paz
Principal Investigator Email
rafael.jose.cobas.paz@sergas.es
Contact Person Name
Rafael Jose Cobas Paz
Site Name
Hospital Son Llatzer
Department Name
Cardiology
Principal Investigator Name
Tomas Ripoll Vera
Principal Investigator Email
tripoll@hsll.es
Contact Person Name
Tomas Ripoll Vera
Contact Person Email
tripoll@hsll.es
Site Name
University Clinical Hospital Virgen De La Arrixaca
Department Name
Cardiology
Principal Investigator Name
Juan Ramon Gimeno Blanes
Principal Investigator Email
jgimeno@secardiologia.es
Contact Person Name
Juan Ramon Gimeno Blanes
Contact Person Email
jgimeno@secardiologia.es
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Cardiology
Principal Investigator Name
Maria Luisa Peña Peña
Principal Investigator Email
marialuisacardio@gmail.com
Contact Person Name
Maria Luisa Peña Peña
Contact Person Email
marialuisacardio@gmail.com
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Cardiology
Principal Investigator Name
Pablo Garcia Pavia
Principal Investigator Email
pablogpavia@yahoo.es
Contact Person Name
Pablo Garcia Pavia
Contact Person Email
pablogpavia@yahoo.es
Site Name
Hospital General Universitario Dr. Balmis
Department Name
Cardiology
Principal Investigator Name
Vicente Eduardo Climent Paya
Principal Investigator Email
vcliment@coma.es
Contact Person Name
Vicente Eduardo Climent Paya
Contact Person Email
vcliment@coma.es
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Cardiology
Principal Investigator Name
Esther Zorio Grima
Principal Investigator Email
zorio_est@gva.es
Contact Person Name
Esther Zorio Grima
Contact Person Email
zorio_est@gva.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Cardiology
Principal Investigator Name
Javier Limeres Freire
Principal Investigator Email
javier.limeres@vallhebron.cat
Contact Person Name
Javier Limeres Freire
Contact Person Email
javier.limeres@vallhebron.cat
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Cardiology
Principal Investigator Name
David Cordero Pereda
Principal Investigator Email
davidcorderopereda@gmail.com
Contact Person Name
David Cordero Pereda
Contact Person Email
davidcorderopereda@gmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Cardiology
Principal Investigator Name
Ana Garcia Alvarez
Principal Investigator Email
anagarci@clinic.cat
Contact Person Name
Ana Garcia Alvarez
Contact Person Email
anagarci@clinic.cat
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Cardiology
Principal Investigator Name
Rafael Jesus Hidalgo Urbano
Principal Investigator Email
rjhidalur@yahoo.es
Contact Person Name
Rafael Jesus Hidalgo Urbano
Contact Person Email
rjhidalur@yahoo.es
Site Name
Hospital Universitario De Salamanca
Department Name
Cardiology
Principal Investigator Name
Luis Miguel Rincon Diaz
Principal Investigator Email
lmrincond@saludcastillayleon.es
Contact Person Name
Luis Miguel Rincon Diaz

Italy

Earliest CTIS Part Ii Submission Date
11-11-2025
Latest Decision Or Authorization Date
20-02-2026
Processing Time Days
101
Number Of Sites
6
Number Of Participants
18

Sites

Site Name
Istituto Auxologico Italiano
Department Name
Unità Operativa di Riabilitazione Cardiologica
Principal Investigator Name
Lia Crotti
Principal Investigator Email
l.crotti@auxologico.it
Contact Person Name
Lia Crotti
Contact Person Email
l.crotti@auxologico.it
Site Name
Policlinico San Donato S.p.A.
Department Name
Cardiologia
Principal Investigator Name
Massimo Francesco Piepoli
Principal Investigator Email
massimo.piepoli@unimi.it
Contact Person Name
Massimo Francesco Piepoli
Contact Person Email
massimo.piepoli@unimi.it
Site Name
Fondazione Toscana Gabriele Monasterio
Department Name
Cardio-Thoracic- UOC Cardiology and cardiovascular medicine
Principal Investigator Name
Giancarlo Todiere
Principal Investigator Email
gtodiere@ftgm.it
Contact Person Name
Giancarlo Todiere
Contact Person Email
gtodiere@ftgm.it
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Advanced Biomedical Sciences Department
Principal Investigator Name
Maria Angela Losi
Principal Investigator Email
losi@unina.it
Contact Person Name
Maria Angela Losi
Contact Person Email
losi@unina.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
Cardiologia 2 - Insufficienza Cardiaca eTrapianti
Principal Investigator Name
Enrico Ammirati
Principal Investigator Email
enrico.ammirati@ospedaleniguarda.it
Contact Person Name
Enrico Ammirati
Site Name
Azienda Ospedaliero Universitaria Careggi
Department Name
Clinica Medica II Piano Cardiologia
Principal Investigator Name
Iacopo Olivotto
Principal Investigator Email
lacopo.olivotto@unifi.it
Contact Person Name
Iacopo Olivotto
Contact Person Email
lacopo.olivotto@unifi.it

Sponsor

Primary sponsor

Full Name
Imbria Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
PPD Development LP
Responsibilities
Multiple sponsor duties (codes: 1,10,11,12,13,2,4,5) as listed in third-party duties
Name
Icon Clinical Research Limited
Responsibilities
Pharmacovigilance; other listed sponsor duties
Name
Suvoda LLC
Responsibilities
Data management/monitoring role (sponsor duties code: 3 as listed)
Name
Medidata Solutions Inc.
Responsibilities
Data platform/solutions (sponsor duties code: 7 as listed)

Third parties

  • {"country":"United States","full_name":"Yale University","duties_or_roles":"Echocardiography core laboratory","organisation_type":"Educational Institution"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Sponsor duties codes: 1,10,11,12,13,2,4,5","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"Sponsor duties code: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties code: 7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Massachusetts General Hospital","duties_or_roles":"Cardiopulmonary exercise testing core laboratory","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Pharmacovigilance and other safety activities (sponsorDuties include pharmacovigilance)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Ninerafaxstat
Active Substance
NINERAFAXSTAT TRIHYDROCHLORIDE MONOHYDRATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus 1 (as listed in product dictionary)
Starting Dose
200 mg MR BID
Dose Levels
200 mg MR BID (max daily dose 400 mg)
Frequency
BID
Maximum Dose
400 mg per day
Investigational Product Name
Tablet, identical in appearance to ninerafaxstat tablets
Modality
Other

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