Clinical trial • Phase III • Cardiology

Acoramidis hydrochloride for Transthyretin amyloid cardiomyopathy (ATTR-CM)

Phase III trial of Acoramidis hydrochloride for Transthyretin amyloid cardiomyopathy (ATTR-CM). open-label. 236 participants.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Transthyretin amyloid cardiomyopathy (ATTR-CM)
Trial Stage
Phase III
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
31-07-2024
First CTIS Authorization Date
29-08-2024

Trial design

open-label Phase III trial across 21 sites in Belgium, Czechia, Denmark and others.

Open Label
Yes
Target Sample Size
236
Trial Duration For Participant
3680

Eligibility

Recruits 236 The CTIS record indicates isVulnerablePopulationSelected=true. Inclusion criterion requires that participants "Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures." No pediatric assent or minor-specific consent procedures are described in the available documents..

Pregnancy Exclusion
8. Females who are pregnant or breastfeeding. A negative urine pregnancy test at the Day 1 visit and at each study visit are required for WOCBP.
Vulnerable Population
The CTIS record indicates isVulnerablePopulationSelected=true. Inclusion criterion requires that participants "Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures." No pediatric assent or minor-specific consent procedures are described in the available documents.

Inclusion criteria

  • {"criterion_text":"- 1. Completed 30 months of the blinded study treatment in Study AG10301 and the Study AG10-301 Month 30 visit including assessments and procedures."}
  • {"criterion_text":"- 2. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures."}
  • {"criterion_text":"- 3. Women of childbearing potential (WOCBP) who engage in heterosexual intercourse must agree to use a highly effective method of contraception beginning with enrollment and continuing for 30 days after the last dose of acoramidis. Female participants using oral contraceptives must agree to use an additional birth control method. While not considered highly effective, a double-barrier method is acceptable. A male participant who is sexually active with a women of childbearing potential and has not had a vasectomy must agree to use a double-barrier method of birth control."}

Exclusion criteria

  • {"criterion_text":"- 1. Has hemodynamic instability, that in the judgment of the Investigator, would pose too great a risk for participation in the study."}
  • {"criterion_text":"- 10. Participation in another interventional clinical trial (with the exception of Study AG10-301) within 30 days prior to dosing. Participation in observational and/or registry studies should be discussed with the Medical Monitor."}
  • {"criterion_text":"- 11. Has any condition that in the opinion of the Investigator or Medical Monitor would preclude compliance with the study protocol such as a history of substance abuse, alcoholism, or a psychiatric condition."}
  • {"criterion_text":"- 2. Has had a heart and/or liver transplant within the year prior to Day 1."}
  • {"criterion_text":"- 3. Has had implantation of a cardiac mechanical assist device (CMAD)."}
  • {"criterion_text":"- 4. Has confirmed diagnosis of light-chain (AL) amyloidosis at any time during Study AG10-301."}
  • {"criterion_text":"- 5. Is on dialysis or has a degree of renal impairment that in the opinion of the Investigator might jeopardize the participant's safety, increase their risk from participation, or interfere with the study."}
  • {"criterion_text":"- 6. Known hypersensitivity to acoramidis, its metabolites, or formulation excipients."}
  • {"criterion_text":"- 7. At the end of Study AG10-301 or at Day 1 of Study AG10-304 (or any time during the study), participant is on prohibited medication."}
  • {"criterion_text":"- 8. Females who are pregnant or breastfeeding. A negative urine pregnancy test at the Day 1 visit and at each study visit are required for WOCBP."}
  • {"criterion_text":"- 9. In the judgment of the Investigator or Medical Monitor, has any clinically important ongoing medical condition or laboratory abnormality or condition that might jeopardize the participant's safety, increase their risk from participation, or interfere with the study."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Safety parameters to be assessed: treatment- emergent serious adverse events (SAEs) and adverse events (AEs), AEs leading to treatment discontinuation, abnormal physical examination findings of clinical relevance, abnormal vital signs of clinical relevance, abnormal electrocardiogram (ECG) parameters of clinical relevance, and changes in clinical safety laboratory parameters of clinical relevance","definition_or_measurement_approach":"Safety parameters as listed in the endpoint text: assessment of treatment-emergent SAEs and AEs, AEs leading to treatment discontinuation, clinically relevant abnormal physical exam findings, vital signs, ECG parameters, and changes in clinical safety laboratory parameters."}

Secondary endpoints

  • {"endpoint_text":"- All-cause mortality and CV mortality","definition_or_measurement_approach":"All-cause mortality and cardiovascular mortality as recorded during study follow-up."}
  • {"endpoint_text":"- Change from Baseline in distance walked during the 6MWT (6MWD)","definition_or_measurement_approach":"Change from baseline in 6-minute walk test distance (6MWD)."}
  • {"endpoint_text":"- Change from Baseline in KCCQ Overall Summary Score (KCCQ-OS)","definition_or_measurement_approach":"Change from baseline in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS)."}
  • {"endpoint_text":"- CV-related hospitalization","definition_or_measurement_approach":"Frequency/incidence of cardiovascular-related hospitalizations during the study."}
  • {"endpoint_text":"- Change from baseline in TTR level (an in vivo measure of TTR stabilization)","definition_or_measurement_approach":"Change from baseline in circulating TTR concentration measured as an in vivo biomarker of TTR stabilization."}
  • {"endpoint_text":"- TTR stabilization measured in established ex vivo assays (FPE and D39Western blot) in the PK-PD substudy","definition_or_measurement_approach":"TTR stabilization assessed using established ex vivo assays (FPE and D39 Western blot) in the PK-PD substudy."}

Recruitment

Planned Sample Size
236
Recruitment Window Months
137
Consent Approach
Written informed consent is required prior to initiation of study procedures: "Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures." Subject information and consent documents are available in multiple languages (examples in the CTIS documents: Dutch, French, Greek, Italian, Portuguese, Spanish, Danish, Czech and English). No pediatric assent is described; pregnancy/partner information forms are provided separately where relevant.

Geography

Total Number Of Sites
21
Total Number Of Participants
213

Belgium

Latest Decision Or Authorization Date
29-08-2024
Number Of Sites
2
Number Of Participants
21

Sites

Site Name
Ziekenhuis Oost Limburg
Department Name
Department of Cardiology
Principal Investigator Name
Matthias Dupont
Principal Investigator Email
matthias.dupont@zol.be
Contact Person Name
Matthias Dupont
Contact Person Email
matthias.dupont@zol.be
Site Name
Az St-Jan Brugge-Oostende A.V.
Department Name
Department of Cardiology
Principal Investigator Name
Philippe Debonnaire
Principal Investigator Email
philippe.debonnaire@azsintjan.be
Contact Person Name
Philippe Debonnaire

Czechia

Latest Decision Or Authorization Date
03-09-2024
Number Of Sites
3
Number Of Participants
22

Sites

Site Name
Institute For Clinical And Experimental Medicine
Department Name
Klinika kardiologie
Principal Investigator Name
Miloš Kubánek
Principal Investigator Email
mikb@ikem.cz
Contact Person Name
Miloš Kubánek
Contact Person Email
mikb@ikem.cz
Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
II. Interní klinika Kardiologie a angiologie
Principal Investigator Name
Tomáš Paleček
Principal Investigator Email
tomas.palecek@vfn.cz
Contact Person Name
Tomáš Paleček
Contact Person Email
tomas.palecek@vfn.cz
Site Name
Fakultni Nemocnice U Sv Anny V Brne
Department Name
I. Interní kardioangiologická klinika
Principal Investigator Name
Jan Krejčí
Principal Investigator Email
jan.krejci@fnusa.cz
Contact Person Name
Jan Krejčí
Contact Person Email
jan.krejci@fnusa.cz

Denmark

Latest Decision Or Authorization Date
30-08-2024
Number Of Sites
1
Number Of Participants
40

Sites

Site Name
Aarhus Universitetshospital
Department Name
Hjertesygdomme – Klinisk Forskning
Principal Investigator Name
Steen Hvitfeldt Poulsen
Principal Investigator Email
steen.hvitfeldt@rm.dk
Contact Person Name
Steen Hvitfeldt Poulsen
Contact Person Email
steen.hvitfeldt@rm.dk

Greece

Latest Decision Or Authorization Date
20-09-2024
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Alexandra Hospital
Department Name
Department of Clinical Therapeutics, Plasma Cell Dyscrasias Unit
Principal Investigator Name
Efstathios Kastritis
Principal Investigator Email
ekastritis@med.uoa.gr
Contact Person Name
Efstathios Kastritis
Contact Person Email
ekastritis@med.uoa.gr

Ireland

Latest Decision Or Authorization Date
29-08-2024
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Mater Misericordiae University Hospital
Department Name
Catherine McAuley Centre
Principal Investigator Name
Emer Joyce
Principal Investigator Email
mater.medicine@ucd.ie
Contact Person Name
Emer Joyce
Contact Person Email
mater.medicine@ucd.ie

Italy

Latest Decision Or Authorization Date
16-10-2024
Number Of Sites
4
Number Of Participants
59

Sites

Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
U.O.C. Medicina Generale 2- Centro Amiloidosi Sistemiche e Malattie ad Alta Complessità
Principal Investigator Name
Laura Piera Obici
Principal Investigator Email
l.obici@smatteo.pv.it
Contact Person Name
Laura Piera Obici
Contact Person Email
l.obici@smatteo.pv.it
Site Name
Fondazione Toscana Gabriele Monasterio
Department Name
Cardio-Thoracic Department FTGM
Principal Investigator Name
Michele Emdin
Principal Investigator Email
emdin@ftgm.it
Contact Person Name
Michele Emdin
Contact Person Email
emdin@ftgm.it
Site Name
Careggi University Hospital
Department Name
Intensive Cardiac Care Unit- SOD Interventistica Cardiologica Strutturale
Principal Investigator Name
Francesco Cappelli
Principal Investigator Email
cappellif@aou-careggi.toscana.it
Contact Person Name
Francesco Cappelli
Site Name
Azienda Unita' Sanitaria Locale Toscana Sud Est
Department Name
Department Cardio Toraco Neuro Vascolare- Area Funzionale Cardiologica
Principal Investigator Name
Michele Ciabatti
Principal Investigator Email
michele.ciabatti1989@gmail.com
Contact Person Name
Michele Ciabatti
Contact Person Email
michele.ciabatti1989@gmail.com

Portugal

Latest Decision Or Authorization Date
02-09-2024
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Unidade Local De Saude De Santa Maria E.P.E.
Department Name
Cardiology Department
Principal Investigator Name
João Agostinho
Principal Investigator Email
joaoragostinho@gmail.com
Contact Person Name
João Agostinho
Contact Person Email
joaoragostinho@gmail.com

Spain

Latest Decision Or Authorization Date
29-08-2024
Number Of Sites
6
Number Of Participants
48

Sites

Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Cardiology
Principal Investigator Name
María Inés Gómez Otero
Principal Investigator Email
Maria.Ines.Gomez.Otero@sergas.es
Contact Person Name
María Inés Gómez Otero
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Cardiology Department
Principal Investigator Name
Julio Nuñez de Villota
Principal Investigator Email
yulnunez@gmail.com
Contact Person Name
Julio Nuñez de Villota
Contact Person Email
yulnunez@gmail.com
Site Name
Clinica Universidad De Navarra
Department Name
Hematology
Principal Investigator Name
Ramon Lecumberri Villamediana
Principal Investigator Email
eecc@unav.es
Contact Person Name
Ramon Lecumberri Villamediana
Contact Person Email
eecc@unav.es
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 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
Clinica Universidad De Navarra
Department Name
Hematology
Principal Investigator Name
Ramon Lecumberri Villamediana
Principal Investigator Email
eecc@unav.es
Contact Person Name
Ramon Lecumberri Villamediana
Contact Person Email
eecc@unav.es

Netherlands

Latest Decision Or Authorization Date
02-09-2024
Number Of Sites
2
Number Of Participants
12

Sites

Site Name
Universitair Medisch Centrum Groningen
Department Name
Cardiologie
Principal Investigator Name
Peter van der Meer
Principal Investigator Email
p.van.der.meer@umcg.nl
Contact Person Name
Peter van der Meer
Contact Person Email
p.van.der.meer@umcg.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Polikliniek Cardiologie
Principal Investigator Name
Marish Oerlemans
Principal Investigator Email
m.i.f.oerlemans-4@umcutrecht.nl
Contact Person Name
Marish Oerlemans

Sponsor

Primary sponsor

Full Name
Eidos Therapeutics Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Multiple sponsor duties (codes: 1,12,15,2,4,6,7,8) including Primary/surrogate endpoint test (code 15)
Name
PRA Hellas CRO A.E.
Responsibilities
CRO (sponsor duties code: 15)

Third parties

  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Sponsor duties codes: 1, 12, 15 (Primary/ surrogate endpoint test), 2, 4, 6, 7, 8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"Sponsor duties codes: 8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"Sponsor duties codes: 3","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Sponsor duties code: 15 (ECG analysis/ review)","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Almac Clinical Services (Ireland) Limited","duties_or_roles":"Sponsor duties code: 15 (IMP Import)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Duke Clinical And Translational Science Institute","duties_or_roles":"Sponsor duties code: 10","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Sponsor duties code: 15 (IMP Import)","organisation_type":"Pharmaceutical company"}
  • {"country":"Greece","full_name":"PRA Hellas CRO A.E.","duties_or_roles":"Sponsor duties code: 15 (CRO)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Acoramidis (AG10)
Active Substance
Acoramidis hydrochloride
Modality
Small molecule
Routes Of Administration
Oral
Route
Oral
Orphan Designation
Yes
Maximum Dose
1424 mg (max daily dose amount as listed)

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