Clinical trial • Phase III • Neurology|Cardiology

Acoramidis hydrochloride for Transthyretin amyloidosis

Phase III trial of Acoramidis hydrochloride for Transthyretin amyloidosis.

Overview

Trial Therapeutic Area
Neurology|Cardiology
Trial Disease
Transthyretin amyloidosis
Trial Stage
Phase III
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
13-09-2024
First CTIS Authorization Date
15-01-2025

Trial design

Randomised, acoramidis hydrochloride matching placebo (placebo arm); dose and schedule not specified in the provided data-controlled Phase III trial in Portugal, Italy, Netherlands and others.

Randomised
Yes
Comparator
Acoramidis Hydrochloride Matching Placebo (placebo arm); dose and schedule not specified in the provided data
Target Sample Size
323

Eligibility

Recruits 323 Vulnerable population is selected for this trial (populationOfTrialSubjects.isVulnerablePopulationSelected = true). All participants "must be willing and able to give a signed informed consent for study procedures. Informed consent must be obtained prior to initiation of study procedures." Minimum age is ≥18 (no provisions for assent or under-18 consent are specified in the provided criteria). Separate ICFs for pregnancy and genetic testing are listed in the dossier (subject information and informed consent form documents)..

Pregnancy Exclusion
19. Female participants who are pregnant or breastfeeding. Females must agree to discontinue breastfeeding before study drug is administered. At Screening, a negative serum pregnancy test must be confirmed at a maximum of 14 days prior to first dose. A negative dipstick urine pregnancy test is also required before any radionuclide cardiac amyloid imaging with SPECT, on Day 1 prior to dosing, and at every In-clinic Visit for WOCBP. A positive urine dipstick pregnancy test will need to be confirmed with a serum test
Vulnerable Population
Vulnerable population is selected for this trial (populationOfTrialSubjects.isVulnerablePopulationSelected = true). All participants "must be willing and able to give a signed informed consent for study procedures. Informed consent must be obtained prior to initiation of study procedures." Minimum age is ≥18 (no provisions for assent or under-18 consent are specified in the provided criteria). Separate ICFs for pregnancy and genetic testing are listed in the dossier (subject information and informed consent form documents).

Inclusion criteria

  • {"criterion_text":"- 1. Participants must be willing and able to give a signed informed consent for study procedures. Informed consent must be obtained prior to initiation of study procedures."}
  • {"criterion_text":"- 2. Male or female ≥ 18 to ≤ 75 years of age inclusive when signing the informed consent. The minimum age requirement will comply with local regulatory requirements."}
  • {"criterion_text":"- 3. Participants must have an established genotype (hetero- or homozygosity) through a medically-genetically indicated test of a TTR gene variant that is known to be pathogenic confirmed by central laboratory prior to randomization. Participants with rare pathogenic TTR variants documented to be cardiac radionuclide uptake negative (eg, S77Y/p.S97Y, Y114C/p.Y134C, E92K/p.E112K, F64L/p.F84L, or other variant) may be included in the trial, provided the participant can be assessed for the primary ATTR-CM endpoint For further details, please refer to the protocol."}
  • {"criterion_text":"- 4. Participant’s age is no more than 10 years (≤ 10) younger than the PADO as determined by pedigree analysis or TTR Variant Actuarial Table for their variant (Scenarios 4A, 4B, or 4C). The participant may be older than PADO. For example, if PADO for a given participant is determined to be 50 years, the age that participant must be is at least 40 years of age (≥ 40) and less than or equal to 75 years of age (≤ 75). Please refer to Genotype Manual for details on calculation of PADO. For further details, please refer to the protocol."}
  • {"criterion_text":"- 5. Agree to the use of highly effective contraception: a. FEMALE: WOCBP (defined as all women physiologically capable of becoming pregnant) who engage in heterosexual intercourse must agree to use a highly effective method of contraception beginning before a radionuclide cardiac amyloid imaging with SPECT is performed during the Screening period and continuing for 30 days after the last dose of study drug. Female participants using oral contraceptives must agree to use an additional birth control method. While not considered highly effective, a double-barrier method is also considered acceptable. b. MALE: A male participant who has not had a vasectomy and is sexually active with a female of childbearing potential must agree to use a double-barrier method of birth control during the study and continue for 30 days after the last dose of study drug. Males must agree to refrain from sperm donation for a minimum of 30 days post the last dose of the study drug."}

Exclusion criteria

  • {"criterion_text":"- 1. Myocardial radionuclide uptake of Grade 1 to Grade 3 on planar imaging with confirmation by SPECT imaging."}
  • {"criterion_text":"- 10. Clinical evidence of untreated hyperthyroidism or hypothyroidism"}
  • {"criterion_text":"- 11. History of type 1 diabetes"}
  • {"criterion_text":"- 12. Known active hepatitis B or C (participants with resolved or cured infection are eligible for enrollment)."}
  • {"criterion_text":"- 13. Known HIV infection."}
  • {"criterion_text":"- 14. History, within the previous 6 months, of nonreversible cardiomyopathy (eg, reversible cardiomyopathy examples include Takotsubo cardiomyopathy, viral cardiomyopathy, ischemic mitral regurgitation), untreated or uncontrolled cardiac arrhythmia, stroke, MI, or ACS"}
  • {"criterion_text":"- 15. Chronic kidney disease, defined as eGFR ≤ 45 mL/min/1.73 m2, undergoing renal dialysis, or status post kidney transplant."}
  • {"criterion_text":"- 16. Abnormal liver function tests at Screening, defined as ALT or AST > 2x ULN or total bilirubin > 2x ULN (or >3x × ULN if known Gilbert’s Disease)."}
  • {"criterion_text":"- 17. Malignancy within 3 years or ongoing malignancy, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated."}
  • {"criterion_text":"- 18. Known hypersensitivity to the study drug (acoramidis or placebo to match) or any of the excipients within."}
  • {"criterion_text":"- 19. Female participants who are pregnant or breastfeeding. Females must agree to discontinue breastfeeding before study drug is administered. At Screening, a negative serum pregnancy test must be confirmed at a maximum of 14 days prior to first dose. A negative dipstick urine pregnancy test is also required before any radionuclide cardiac amyloid imaging with SPECT, on Day 1 prior to dosing, and at every In-clinic Visit for WOCBP. A positive urine dipstick pregnancy test will need to be confirmed with a serum test"}
  • {"criterion_text":"- 2. Evidence of ATTR-PN (including autonomic neuropathy) by SNAC examination or skin biopsy."}
  • {"criterion_text":"- 20. In the judgment of the Investigator or Medical Monitor, has any clinically relevant ongoing medical condition or laboratory abnormality or other condition that might jeopardize the participant’s safety, increase the participant’s risk from participation, interfere with the study, or confound study results"}
  • {"criterion_text":"- 21. Participation in another investigational clinical trial within 30 days prior to Screening or within 5 half-lives of any non-ATTR investigational agent (or within the timeframe specified in Exclusion Criterion #7 for ATTR investigational agents) whichever is longer. Participation in observational and/or registry studies must be discussed with the Medical Monitor."}
  • {"criterion_text":"- 22. 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":"- 23. Major surgery as defined by the Investigator within the past 3 months or planned during the next 12 months."}
  • {"criterion_text":"- 3. Known history of AL amyloidosis or another non-TTR amyloid subtype (eg, ApoA-1, gelsolin)."}
  • {"criterion_text":"- 4. History of a monoclonal paraprotein or abnormal light chains in serum or urine (ie, MGUS) in which AL has not been ruled out."}
  • {"criterion_text":"- 5. Pre-existing diagnosis of axonal neuropathy from a non-amyloid cause (eg, established diagnosis of diabetic peripheral neuropathy, presence of alcohol-related neuropathy)"}
  • {"criterion_text":"- 6. Presence of a TTR variant known to be phenotypically protective (eg, T119M, R104H)"}
  • {"criterion_text":"- 7. Contraindication to or inability to undergo CMR testing"}
  • {"criterion_text":"- 8. Presence of condition known to generate false positive myocardial radionuclide uptake with SPECT imaging (eg, ApoA-1 amyloidosis, chronic hydroxychloroquine use)."}
  • {"criterion_text":"- 9. Comorbidity or condition that is likely to result in a life expectancy of < 10 years based on clinical judgment of the Investigator."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1. Time to development of ATTR (ATTR-CM or ATTR-PN, whichever occurs first). For further details, please refer to the protocol.","definition_or_measurement_approach":"For further details, please refer to the protocol."}

Secondary endpoints

  • {"endpoint_text":"- 1. Time to development of ATTR-CM and ATTR-PN. For further details, please refer to the protocol.","definition_or_measurement_approach":"For further details, please refer to the protocol."}
  • {"endpoint_text":"- 2. Participants who develop ATTR as defined in the primary endpoint at the time of study completion (yes/no)","definition_or_measurement_approach":"Binary outcome assessed at study completion; see protocol for operational definition."}
  • {"endpoint_text":"- 3. Time to development of symptomatic ATTR and ATTR-CM","definition_or_measurement_approach":"Time-to-event outcome; see protocol for symptom and diagnostic criteria."}
  • {"endpoint_text":"- 4. Participants who develop symptomatic ATTR","definition_or_measurement_approach":"Binary outcome; see protocol for symptom definition and adjudication."}
  • {"endpoint_text":"- 5. Proportion of participants with: treatment-emergent AEs and SAEs, AEs leading to treatment discontinuation, abnormal physical examination findings of clinical relevance, abnormal vital signs of clinical relevance, abnormal ECG parameters of clinical relevance, changes in clinical safety laboratory parameters of potential concern","definition_or_measurement_approach":"Safety and tolerability outcomes summarized as proportions; see protocol for AE definitions, grading and assessment windows."}

Recruitment

Planned Sample Size
323
Recruitment Window Months
82
Consent Approach
Signed informed consent is required prior to initiation of study procedures. Subject information and informed consent forms (main ICF) are provided; additional ICFs for pregnancy and genetic testing are included in the dossier. Minimum age for consent is ≥18. Country-specific ICFs and patient materials are provided (multiple country-specific SIS/ICF documents listed).

Geography

Total Number Of Sites
37
Total Number Of Participants
314

Portugal

Earliest CTIS Part Ii Submission Date
02-10-2024
Latest Decision Or Authorization Date
14-03-2025
Processing Time Days
163
Number Of Sites
2
Number Of Participants
29

Sites

Site Name
Unidade Local De Saude De Santo Antonio E.P.E.
Department Name
Neurophysiology Department
Contact Person Name
Márcio Cardoso
Site Name
Unidade Local De Saude De Santa Maria E.P.E.
Department Name
Department of Neurosciences
Contact Person Name
Isabel Conceição
Contact Person Email
imsconceicao@gmail.com

Italy

Earliest CTIS Part Ii Submission Date
02-10-2024
Latest Decision Or Authorization Date
03-04-2025
Processing Time Days
183
Number Of Sites
8
Number Of Participants
49

Sites

Site Name
Fondazione Toscana Gabriele Monasterio
Department Name
cardiology
Contact Person Name
Alberto Aimo
Contact Person Email
aimoalb@ftgm.it
Site Name
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Department Name
Neurology
Contact Person Name
Anna Mazzeo
Contact Person Email
annamazzeo@yahoo.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
cardiology
Contact Person Name
Simone Longhi
Contact Person Email
simone.longhi@aosp.bo.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
rare diseases
Contact Person Name
Laura Piera Obici
Contact Person Email
l.obici@smatteo.pv.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
Cardiovascular
Contact Person Name
Cristina Chimenti
Contact Person Email
cristina.chimenti@uniroma1.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
neurology
Contact Person Name
Marco Luigetti
Site Name
Careggi University Hospital
Department Name
cardiology
Contact Person Name
Francesco Cappelli
Contact Person Email
f.cappelli@unifi.it
Site Name
Azienda Ospedaliero-Universitaria Sant Andre
Department Name
neurology
Contact Person Name
Luca Leonardi
Contact Person Email
leonardi.luca89@gmail.com

Netherlands

Earliest CTIS Part Ii Submission Date
08-01-2025
Latest Decision Or Authorization Date
10-04-2025
Processing Time Days
92
Number Of Sites
4
Number Of Participants
9

Sites

Site Name
Universitair Medisch Centrum Groningen
Department Name
Internal Medicine
Contact Person Name
Hans Nienhuis
Contact Person Email
h.l.a.nienhuis@umcg.nl
Site Name
Academisch Ziekenhuis Maastricht
Department Name
Cardiology
Contact Person Name
Christian Knackstedt
Contact Person Email
c.knackstedt@mumc.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Cardiology
Contact Person Name
Marish Oerlemans
Contact Person Email
m.oerlemans@umcutrecht.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Cardiology
Contact Person Name
Michelle Michels
Contact Person Email
m.michels@erasmusmc.nl

Germany

Earliest CTIS Part Ii Submission Date
08-11-2024
Latest Decision Or Authorization Date
07-03-2025
Processing Time Days
119
Number Of Sites
3
Number Of Participants
27

Sites

Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
Studienzentrum der Klinik und Poliklinik für Neurologie
Contact Person Name
Frank Birklein
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für Kardiologie, Angiologie und Intensivsmedizin
Contact Person Name
Katrin Hahn
Contact Person Email
katrin.hahn@charite.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Neurologische Klinik
Contact Person Name
Markus Weiler

Bulgaria

Earliest CTIS Part Ii Submission Date
10-01-2025
Latest Decision Or Authorization Date
18-03-2025
Processing Time Days
67
Number Of Sites
1
Number Of Participants
7

Sites

Site Name
Alexandrovska University Hospital
Department Name
Clinic for neurological diseases
Contact Person Name
Ivaylo Tournev

Ireland

Earliest CTIS Part Ii Submission Date
15-04-2025
Latest Decision Or Authorization Date
23-05-2025
Processing Time Days
38
Number Of Sites
2
Number Of Participants
15

Sites

Site Name
Mater Misericordiae University Hospital
Department Name
Cardiology
Contact Person Name
Emer Joyce
Contact Person Email
emerjoyce@mater.ie
Site Name
Tallaght University Hospital
Department Name
Neurology
Contact Person Name
Sinead Murphy
Contact Person Email
Sinead.murphy@tuh.ie

Sweden

Earliest CTIS Part Ii Submission Date
09-05-2025
Latest Decision Or Authorization Date
26-05-2025
Processing Time Days
17
Number Of Sites
1
Number Of Participants
14

Sites

Site Name
Region Vaesterbotten
Department Name
Amyloidosis center E41, Forsorjningsvagen 1 C, S-901 85, Umea
Contact Person Name
Jonas Wixner
Contact Person Email
Jonas.wixner@umu.se

Denmark

Earliest CTIS Part Ii Submission Date
06-06-2025
Latest Decision Or Authorization Date
13-06-2025
Processing Time Days
7
Number Of Sites
1
Number Of Participants
7

Sites

Site Name
Region Midtjylland
Department Name
Department of Cardiology, Aarhus University Hospital
Contact Person Name
Steen Hvitfeldt Poulsen
Contact Person Email
steen.hvitfeldt@rm.dk

Greece

Earliest CTIS Part Ii Submission Date
13-05-2025
Latest Decision Or Authorization Date
25-06-2025
Processing Time Days
43
Number Of Sites
2
Number Of Participants
20

Sites

Site Name
Hippokration Hospital
Department Name
1st Cardiology Department, National and Kapodistrian University of Athens
Contact Person Name
Charalambos Vlachopoulos
Contact Person Email
ekkan@med.uoa.gr
Site Name
Alexandra Hospital
Department Name
Center of Expertise in Amyloidosis,Plasma Cell Dyscrasias U/Hem-Onc U,Dpt Clinical Ther,Med Sch NKUA
Contact Person Name
Efstathios Kastritis
Contact Person Email
ekastritis@med.uoa.gr

Belgium

Earliest CTIS Part Ii Submission Date
14-07-2025
Latest Decision Or Authorization Date
24-07-2025
Processing Time Days
10
Number Of Sites
1
Number Of Participants
13

Sites

Site Name
UZ Leuven
Department Name
Neurology
Contact Person Name
Kristl G. H. Claeys
Contact Person Email
kristl.claeys@uzleuven.be

Spain

Earliest CTIS Part Ii Submission Date
10-01-2025
Latest Decision Or Authorization Date
18-11-2025
Processing Time Days
312
Number Of Sites
6
Number Of Participants
60

Sites

Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Cardiology
Contact Person Name
Esther González López
Contact Person Email
esthgonzalez@hotmail.com
Site Name
Hospital Son Llatzer
Department Name
Internal medicine
Contact Person Name
Juan Gonzalez Moreno
Contact Person Email
jgonzalez4@hsll.es
Site Name
Hospital Universitario Juan Ramon Jimenez
Department Name
Internal medicine
Contact Person Name
Cristina Borrachero Garro
Site Name
Hospital Universitario De Salamanca
Department Name
Cardiology
Contact Person Name
Rocio Eiros Bachiller
Contact Person Email
reirosb@saludcastillayleon.es
Site Name
Bellvitge University Hospital
Department Name
Cardiology
Contact Person Name
Jose Gonzalez-Costello
Site Name
Area Sanitaria Da Coruna E Cee
Department Name
Cardiology
Contact Person Name
Roberto Barriales Villa
Contact Person Email
rbarrialesv@gmail.com

France

Earliest CTIS Part Ii Submission Date
06-12-2024
Latest Decision Or Authorization Date
11-12-2025
Processing Time Days
370
Number Of Sites
6
Number Of Participants
64

Sites

Site Name
Pellegrin Hospital
Department Name
Neurology
Contact Person Name
Guilhem Sole
Contact Person Email
guilhem.sole@chu-bordeaux.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
cardiology
Contact Person Name
olivier Lairez
Contact Person Email
lairez.o@chu-toulouse.fr
Site Name
CHU De Martinique
Department Name
cardiology
Contact Person Name
Jocelyn Inamo
Contact Person Email
Inamo_jocelyn@yahoo.com
Site Name
Hopital Henri Mondor - 1 rue Gustave Eiffel
Department Name
cardiology
Contact Person Name
Thibaud Damy
Contact Person Email
thibaud.damy@aphp.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
cardiology
Contact Person Name
Erwan Donal
Contact Person Email
erwan.donal@chu-rennes.fr
Site Name
Bicetre Hospital
Department Name
Neurology
Contact Person Name
Andoni Echaniz-Laguna
Contact Person Email
andoni.echaniz-laguna@aphp.fr

Sponsor

Primary sponsor

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

Contract research organisations

Name
Medpace Finland Oy
Responsibilities
Safety Labs, sample management; other sponsor duties coded 1,12,4
Name
Medpace Ellas Monoprosopi I.K.E.
Responsibilities
Site-related responsibilities (codes 1,12)
Name
Almac Clinical Services LLC
Responsibilities
IVRS & Randomization, IP Depot Distribution and Packaging
Name
United Biosource LLC
Responsibilities
safety database
Name
Allucent (US) LLC
Responsibilities
Data Flow Mapping for GDPR
Name
Eresearchtechnology Inc.
Responsibilities
Central ECG Reader

Third parties

  • {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Codes: 1,12,15 (Safety Labs, sample management),4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"safety database","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Allucent (US) LLC","duties_or_roles":"Data Flow Mapping for GDPR","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central ECG Reader","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"IVRS & Randomization, IP Depot Distribution and Packaging; codes: 14,15,3","organisation_type":"Pharmaceutical company"}
  • {"country":"Greece","full_name":"Medpace Ellas Monoprosopi I.K.E.","duties_or_roles":"Codes: 1,12","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Acoramidis (AG10)
Active Substance
Acoramidis hydrochloride
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
prodAuthStatus=1 (as recorded in product dictionary)
Orphan Designation
Yes
Maximum Dose
1424 mg (maxDailyDoseAmount)
Investigational Product Name
Acoramidis Hydrochloride Matching Placebo
Modality
Other

Related trials

Other published trials that may interest you.