Clinical trial • Phase III • Cardiology

Vutrisiran for Transthyretin amyloidosis with cardiomyopathy (ATTR amyloidosis with cardiomyopathy)

Phase III trial of Vutrisiran for Transthyretin amyloidosis with cardiomyopathy (ATTR amyloidosis with cardiomyopathy).

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Transthyretin amyloidosis with cardiomyopathy (ATTR amyloidosis with cardiomyopathy)
Trial Stage
Phase III
Drug Modality
Oligonucleotide
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
04-10-2024
First CTIS Authorization Date
28-01-2025

Trial design

open-label, none/not specified-controlled Phase III trial in Austria, Belgium, Czechia and others.

Open Label
Yes
Comparator
None/Not specified
Target Sample Size
526
Trial Duration For Participant
1095

Eligibility

Recruits 526 Vulnerable population selected. Inclusion criteria state: 'Patient or legal guardian, where relevant and allowable by law, is able to understand and is willing and able to comply with the study requirements and to provide written informed consent.' Consent may be provided by a legal guardian where relevant and allowable by law. (No specific assent procedures for minors are described in the provided data.).

Pregnancy Exclusion
6. Female patient is pregnant, planning a pregnancy, or breast-feeding.
Vulnerable Population
Vulnerable population selected. Inclusion criteria state: 'Patient or legal guardian, where relevant and allowable by law, is able to understand and is willing and able to comply with the study requirements and to provide written informed consent.' Consent may be provided by a legal guardian where relevant and allowable by law. (No specific assent procedures for minors are described in the provided data.)

Inclusion criteria

  • {"criterion_text":"- 1. Patients with ATTR amyloidosis (hereditary or wt) who are participating in the patisiran parent studies ALN-TTR02-011 or ALN-TTR02-014 or who have completed the 24-month OLE Period in the vutrisiran parent study ALN-TTRSC02-003."}
  • {"criterion_text":"- 2. Willingness to adhere to vitamin A supplementation per protocol."}
  • {"criterion_text":"- 3. Patient or legal guardian, where relevant and allowable by law, is able to understand and is willing and able to comply with the study requirements and to provide written informed consent."}

Exclusion criteria

  • {"criterion_text":"- 1. Permanently discontinued study drug administration while participating in the parent studies, Study ALN-TTR02-011, Study ALN-TTR02-014, or Study ALN-TTRSC02-003."}
  • {"criterion_text":"- 2. Future or current participation in another investigational device or drug study, scheduled to occur during this study."}
  • {"criterion_text":"- 3. Requires treatment with or is unwilling to avoid any concurrent treatment with non-dihydropyridine calcium channel blockers (eg, verapamil, diltiazem)."}
  • {"criterion_text":"- 4. Has other medical conditions or comorbidities (eg, malignancy, neuropsychiatric disorder) which, in the opinion of the Investigator, would interfere with study compliance or data interpretation."}
  • {"criterion_text":"- 5. Is not willing to comply with the contraceptive requirements during the study period."}
  • {"criterion_text":"- 6. Female patient is pregnant, planning a pregnancy, or breast-feeding."}
  • {"criterion_text":"- 7. Unwilling or unable to limit alcohol consumption throughout the course of the study. Alcohol intake of >2 units/day is excluded during the study (unit: 1 glass of wine [approximately 125 mL] = 1 measure of spirits [approximately 1 fluid ounce] = ½ pint of beer [approximately 284 mL])."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Frequency of adverse events","definition_or_measurement_approach":"Safety assessed throughout the study as outlined in the schedule of assessments; patients continually assessed for adverse events and concomitant medications. Other safety assessments include laboratory testing and pregnancy testing; AEs recorded per schedule."}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline in KCCQ-OS score","definition_or_measurement_approach":"Efficacy assessed q6M using the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score; change from baseline measured per schedule of assessments."}
  • {"endpoint_text":"- Change from baseline in NYHA class","definition_or_measurement_approach":"NYHA classification assessed q6M; change from baseline in NYHA class recorded as specified in the schedule of assessments."}
  • {"endpoint_text":"- Change from baseline in cardiac biomarkers (NT-proBNP and troponin I)","definition_or_measurement_approach":"Cardiac biomarkers NT-proBNP and troponin I measured per schedule; change from baseline assessed."}
  • {"endpoint_text":"- All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits)","definition_or_measurement_approach":"All-cause mortality and cardiovascular events (hospitalizations and urgent heart failure visits) are recorded and adjudicated per protocol; assessed as event counts over follow-up."}
  • {"endpoint_text":"- Change from baseline in serum TTR level","definition_or_measurement_approach":"Pharmacodynamic assessment of serum transthyretin (TTR) at Months 6 and 12; change from baseline in serum TTR level measured per PD schedule."}

Recruitment

Planned Sample Size
526
Recruitment Window Months
28
Consent Approach
Written informed consent is required from the patient; where relevant and allowable by law a legal guardian may provide consent. Country-specific subject information and ICF documents are provided (multiple language versions and country-specific ICFs are listed in the trial documents). Available ICF/material languages and versions include English, German, Dutch, French, Portuguese, Spanish, Italian, Swedish, Czech, Norwegian, Danish and country-specific participant and partner ICFs and information materials (as per the provided document list).

Geography

Total Number Of Sites
40
Total Number Of Participants
208

Austria

Earliest CTIS Part Ii Submission Date
24-01-2025
Latest Decision Or Authorization Date
19-04-2026
Processing Time Days
450
Number Of Sites
2
Number Of Participants
9

Sites

Site Name
Medical University Of Vienna
Department Name
Internal Medicine II - Division for Cardiology
Principal Investigator Name
Johannes Kastner
Principal Investigator Email
johannes.kastner@meduniwien.ac.at
Contact Person Name
Johannes Kastner
Site Name
Stadt Wien Wiener Gesundheitsverbund
Department Name
Karl Landsteiner Institute for Cardiovascular and Critical Care Research
Principal Investigator Name
Andreas Schober
Principal Investigator Email
andreas.schober@gesundheitsverbund.at
Contact Person Name
Andreas Schober

Belgium

Earliest CTIS Part Ii Submission Date
19-12-2024
Latest Decision Or Authorization Date
07-04-2026
Processing Time Days
474
Number Of Sites
8
Number Of Participants
19

Sites

Site Name
Hopital Erasme
Department Name
Cardiology
Principal Investigator Name
Antoine Bondue
Principal Investigator Email
antoine.bondue@hubruxelles.be
Contact Person Name
Antoine Bondue
Contact Person Email
antoine.bondue@hubruxelles.be
Site Name
Algemeen Ziekenhuis Delta
Department Name
Cardiology
Principal Investigator Name
Karl Dujardin
Principal Investigator Email
karl.dujardin@azdelta.be
Contact Person Name
Karl Dujardin
Contact Person Email
karl.dujardin@azdelta.be
Site Name
Onze-Lieve-Vrouwziekenhuis
Department Name
Cardiology
Principal Investigator Name
Marc Vanderheyden
Principal Investigator Email
marc.vanderheyden@olvz-aalst.be
Contact Person Name
Marc Vanderheyden
Site Name
UZ Leuven
Department Name
Cardiology
Principal Investigator Name
Lucas Van Aelst
Principal Investigator Email
lucas.vanaelst@med.kuleuven.be
Contact Person Name
Lucas Van Aelst
Contact Person Email
lucas.vanaelst@med.kuleuven.be
Site Name
Universitair Ziekenhuis Gent
Department Name
Cardiology
Principal Investigator Name
Michel De Pauw
Principal Investigator Email
michel.depauw@ugent.be
Contact Person Name
Michel De Pauw
Contact Person Email
michel.depauw@ugent.be
Site Name
Jessa Ziekenhuis
Department Name
Cardiology
Principal Investigator Name
Philippe Timmermans
Principal Investigator Email
Philippe.Jr.Timmermans@jessazh.be
Contact Person Name
Philippe Timmermans
Site Name
Centre Hospitalier Regional De La Citadelle
Department Name
Cardiology
Principal Investigator Name
Pierre Troisfontaines
Principal Investigator Email
pierre.troisfontaines@citadelle.be
Contact Person Name
Pierre Troisfontaines
Site Name
O.L.Vrouw van Troost
Department Name
Cardiology
Principal Investigator Name
Tom Sarens
Principal Investigator Email
tomsarens@hotmail.com
Contact Person Name
Tom Sarens
Contact Person Email
tomsarens@hotmail.com

Czechia

Earliest CTIS Part Ii Submission Date
08-01-2025
Latest Decision Or Authorization Date
25-03-2026
Processing Time Days
441
Number Of Sites
3
Number Of Participants
11

Sites

Site Name
Synexus Czech s.r.o.
Principal Investigator Name
Iva Škarpová
Principal Investigator Email
iva.skarpova@synexus.com
Contact Person Name
Iva Škarpová
Contact Person Email
iva.skarpova@synexus.com
Site Name
Institute For Clinical And Experimental Medicine
Department Name
Klinika kardiologie
Principal Investigator Name
Miloš Kubánek
Principal Investigator Email
mikb@medicon.cz
Contact Person Name
Miloš Kubánek
Contact Person Email
mikb@medicon.cz
Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
Interní klinika - 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

Denmark

Earliest CTIS Part Ii Submission Date
08-01-2025
Latest Decision Or Authorization Date
07-04-2026
Processing Time Days
454
Number Of Sites
3
Number Of Participants
24

Sites

Site Name
Region Midtjylland
Department Name
Klinisk forskningsenhed, Hjertesygdomme (department of cardiology)
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
Site Name
Rigshospitalet
Department Name
Cardiology
Principal Investigator Name
Kasper Rossing
Principal Investigator Email
kasper.rossing@regionh.dk
Contact Person Name
Kasper Rossing
Contact Person Email
kasper.rossing@regionh.dk
Site Name
Odense University Hospital
Department Name
Kardiologisk Forskningsenhed
Principal Investigator Name
Jens Flensted Lassen
Principal Investigator Email
Jens.flensted.lassen@rsyd.dk
Contact Person Name
Jens Flensted Lassen
Contact Person Email
Jens.flensted.lassen@rsyd.dk

France

Earliest CTIS Part Ii Submission Date
07-01-2025
Latest Decision Or Authorization Date
18-03-2026
Processing Time Days
435
Number Of Sites
5
Number Of Participants
30

Sites

Site Name
Centre Hospitalier Regional De Marseille
Department Name
Service de Cardiologie
Principal Investigator Name
Gilbert Habib
Principal Investigator Email
gilbert.habib@ap-hm.fr
Contact Person Name
Gilbert Habib
Contact Person Email
gilbert.habib@ap-hm.fr
Site Name
Assistance Publique Hopitaux De Paris (Creteil Cedex)
Department Name
Département de Cardiologie
Principal Investigator Name
Thibaud Damy
Principal Investigator Email
amira.zaroui@aphp.fr
Contact Person Name
Thibaud Damy
Contact Person Email
amira.zaroui@aphp.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Service de Cardiologie
Principal Investigator Name
Pauline Fournier
Principal Investigator Email
fournier.p@chu-toulouse.fr
Contact Person Name
Pauline Fournier
Contact Person Email
fournier.p@chu-toulouse.fr
Site Name
Assistance Publique Hopitaux De Paris (Paris Cedex 18)
Department Name
Département de Cardiologie
Principal Investigator Name
Vincent Algalarrondo
Principal Investigator Email
vincent.algalarrondo@aphp.fr
Contact Person Name
Vincent Algalarrondo
Contact Person Email
vincent.algalarrondo@aphp.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Service de Cardiologie et Maladie Vasculaires
Principal Investigator Name
Erwan Donal
Principal Investigator Email
erwan.donal@chu-rennes.fr
Contact Person Name
Erwan Donal
Contact Person Email
erwan.donal@chu-rennes.fr

Italy

Earliest CTIS Part Ii Submission Date
03-01-2025
Latest Decision Or Authorization Date
20-04-2026
Processing Time Days
472
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
U.O.C. Med. Gen. 2 - Centro Amiloidosi Sistemiche Malattie ad Alta Complessità - S.S. Malattie Rare
Principal Investigator Name
Laura Obici
Principal Investigator Email
l.obici@smatteo.pv.it
Contact Person Name
Laura Obici
Contact Person Email
l.obici@smatteo.pv.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
U.O. Cardiologia
Principal Investigator Name
Igor Diemberger
Principal Investigator Email
igor.diemberger@unibo.it
Contact Person Name
Igor Diemberger
Contact Person Email
igor.diemberger@unibo.it
Site Name
Careggi University Hospital
Department Name
Centro di Riferimento regionale per lo studio di Amiloidosi - SOD Medicina Sperimentale e Clinica
Principal Investigator Name
Francesco Cappelli
Principal Investigator Email
cappellif@aou-careggi.toscana.it
Contact Person Name
Francesco Cappelli

Netherlands

Earliest CTIS Part Ii Submission Date
06-01-2025
Latest Decision Or Authorization Date
11-05-2026
Processing Time Days
490
Number Of Sites
3
Number Of Participants
20

Sites

Site Name
Universitair Medisch Centrum Utrecht
Department Name
Cardiology
Principal Investigator Name
Marish Oerlemans
Principal Investigator Email
researchdhl@umcutrecht.nl
Contact Person Name
Marish Oerlemans
Contact Person Email
researchdhl@umcutrecht.nl
Site Name
Universitair Medisch Centrum Groningen
Department Name
Cardiology
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
Academisch Ziekenhuis Maastricht
Department Name
Cardiology
Principal Investigator Name
Christian Knackstedt
Principal Investigator Email
c.knackstedt@mumc.nl
Contact Person Name
Christian Knackstedt
Contact Person Email
c.knackstedt@mumc.nl

Norway

Earliest CTIS Part Ii Submission Date
24-01-2025
Latest Decision Or Authorization Date
24-03-2026
Processing Time Days
424
Number Of Sites
1
Number Of Participants
11

Sites

Site Name
Oslo University Hospital HF
Department Name
Kardiologisk avd
Principal Investigator Name
Kaspar Broch
Principal Investigator Email
sbbrok@ous-hf.no
Contact Person Name
Kaspar Broch
Contact Person Email
sbbrok@ous-hf.no

Portugal

Earliest CTIS Part Ii Submission Date
19-11-2024
Latest Decision Or Authorization Date
18-03-2026
Processing Time Days
484
Number Of Sites
4
Number Of Participants
16

Sites

Site Name
Unidade Local De Saude Do Alto Ave E.P.E.
Department Name
Cardiology
Principal Investigator Name
Olga Azevedo
Contact Person Name
Olga Azevedo
Site Name
Unidade Local De Saude De Viseu Dao-Lafoes E.P.E.
Department Name
Cardiology
Principal Investigator Name
Emanuel Correia
Principal Investigator Email
emanuelbaptista@gmail.com
Contact Person Name
Emanuel Correia
Contact Person Email
emanuelbaptista@gmail.com
Site Name
Unidade Local De Saude De Santa Maria E.P.E.
Department Name
Cardiology
Principal Investigator Name
Dulce Brito
Principal Investigator Email
dulcebrito59@gmail.com
Contact Person Name
Dulce Brito
Contact Person Email
dulcebrito59@gmail.com
Site Name
Unidade Local De Saude De Santo Antonio E.P.E.
Department Name
Cardiology
Principal Investigator Name
Patricia Rodrigues
Principal Investigator Email
pfdrodrigues@gmail.com
Contact Person Name
Patricia Rodrigues
Contact Person Email
pfdrodrigues@gmail.com

Spain

Earliest CTIS Part Ii Submission Date
07-01-2025
Latest Decision Or Authorization Date
26-03-2026
Processing Time Days
443
Number Of Sites
5
Number Of Participants
44

Sites

Site Name
Bellvitge University Hospital
Department Name
Cardiology Department
Principal Investigator Name
José González Costello
Principal Investigator Email
jgonzalez@bellvitgehospital.cat
Contact Person Name
José González Costello
Site Name
Hospital Universitario Basurto
Department Name
Cardiolog Department
Principal Investigator Name
Ainara Lozano Bahamonde
Principal Investigator Email
ainara.lozanobahamonde@osakidetza.eus
Contact Person Name
Ainara Lozano Bahamonde
Site Name
Hospital Universitari Vall D Hebron
Department Name
Internal Medicine Department
Principal Investigator Name
Fernando Martínez Valle
Principal Investigator Email
fernando.martinez@vallhebron.cat
Contact Person Name
Fernando Martínez Valle
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Cardiology Department
Principal Investigator Name
José Manuel García Pinilla
Principal Investigator Email
pinilla@secardiologia.es
Contact Person Name
José Manuel García Pinilla
Contact Person Email
pinilla@secardiologia.es
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Cardiology Department
Principal Investigator Name
Pablo García Pavia
Principal Investigator Email
pablogpavia@yahoo.es
Contact Person Name
Pablo García Pavia
Contact Person Email
pablogpavia@yahoo.es

Sweden

Earliest CTIS Part Ii Submission Date
03-01-2025
Latest Decision Or Authorization Date
10-04-2026
Processing Time Days
462
Number Of Sites
3
Number Of Participants
15

Sites

Site Name
Region Vaesterbotten
Department Name
Kliniskt Forskningscentrum
Principal Investigator Name
Björn Pilebro
Principal Investigator Email
bjorn.pilebro@regionvasterbotten.se
Contact Person Name
Björn Pilebro
Site Name
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Department Name
Kardiologens Forskningsenhet
Principal Investigator Name
Entela Bollano
Principal Investigator Email
entela.bollano@vgregion.se
Contact Person Name
Entela Bollano
Contact Person Email
entela.bollano@vgregion.se
Site Name
Karolinska University Hospital
Department Name
ME Kardiologi, Tema Hjärta Kärl
Principal Investigator Name
Per Eldhagen
Principal Investigator Email
per.eldhagen@regionstockholm.se
Contact Person Name
Per Eldhagen

Sponsor

Primary sponsor

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

Contract research organisations

Name
Advanced Clinical LLC
Responsibilities
sponsorDuties codes: 6, 7
Name
PPD Development LP
Responsibilities
sponsorDuties codes: 1, 12, 13, 15 (Vendor Management, Client Supplies), 2, 4, 5, 8
Name
Suvoda LLC
Responsibilities
sponsorDuties code: 3

Third parties

  • {"country":"United States","full_name":"Advanced Clinical LLC","duties_or_roles":"sponsorDuties codes: 6, 7","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: 1, 12, 13, 15 (value: Vendor Management, Client Supplies), 2, 4, 5, 8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"EPL Pathology Archives LLC","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"sponsorDuties code: 15 (value: Patient support services (travel, meal, reimbursement etc))","organisation_type":"Pharmaceutical company"}
  • {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Amvuttra 25 mg solution for injection in pre-filled syringe
Active Substance
Vutrisiran
Modality
Oligonucleotide
Routes Of Administration
Subcutaneous
Route
Subcutaneous
Authorisation Status
Authorised (marketing authorisation EU/1/22/1681/001)
Orphan Designation
Yes
Starting Dose
25 mg
Dose Levels
25 mg
Frequency
Once every 3 months (q3M)
Maximum Dose
Max daily dose 25 mg; max total dose 325 mg

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