Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
734
Countries
11
Sites
40
Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)
To obtain safety data on the use of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy who o continued on extended use of vutrisiran, or o switched from patisiran
Key facts
- Sponsor
- Alnylam Pharmaceuticals Inc.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 12 Feb 2025 → ongoing
- Decision date (initial)
- 2025-01-31
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Alnylam Pharmaceuticals, Inc.
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Pharmacodynamic, Efficacy, Others
To obtain safety data on the use of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy who
o continued on extended use of vutrisiran, or
o switched from patisiran
Secondary objectives 2
- To obtain efficacy data on the use of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy who o continued on extended use of vutrisiran, or o switched from patisiran
- To obtain PD data on the use of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy who o continued on extended use ofvutrisiran, or o switched from patisiran
Conditions and MedDRA coding
Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 27.0 | PT | 10007509 | Cardiac amyloidosis | 100000004849 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Open-Label Treatment Period This is a multicenter, multinational, single-arm, Phase 3b open-label extension study designed to evaluate the safety, efficacy, and pharmacodynamics (PD) of 25 mg subcutaneous (SC) vutrisiran in patients with ATTR amyloidosis with cardiomyopathy (hereditary or wild-type [wt]) who are actively participating in the patisiran parent studies ALN-TTR02-011 or ALNTTR02-014 or who have completed the 24-month open-label extension (OLE) Period in the vutrisiran parent study ALN-TTRSC02-003.
Baseline assessments for the study are collected on Day 1; however, if the same assessments were collected in the parent study within 45 days of Day 1 in current study, they may serve as baseline assessments.
The first dose of study drug should be administered on Study Day 1 after all assessments have been completed and eligibility confirmed. After the Day 1 visit, patients should return to the site for vutrisiran dosing and study assessments once every 3 months (q3M). Assessments should be completed before vutrisiran is administered.
Safety will be assessed throughout the study as outlined in the schedule of assessments (SOA). Patients will be continually assessed throughout the study for adverse events (AEs) and concomitant medications. Other safety assessments will include laboratory testing and
pregnancy testing.
Efficacy assessments will be done q6M as outlined in the SOA. The efficacy of vutrisiran will be assessed through Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score, New York Heart Association (NYHA) classification of heart failure, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and troponin I, all-cause mortality, cardiovascular related hospitalizations, and urgent heart failure (HF) visits.
Pharmacodynamic assessments will be done at Months 6 and 12 as outlined in the SOA. Pharmacodynamics will be assessed by change from baseline in serum transthyretin (TTR).
|
Not Applicable | None |
Regulatory references
- Plan to share IPD
- Yes
- IPD plan description
- Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
| EU CT number | Title | Sponsor |
|---|---|---|
| 2019-003153-28 | HELIOS-B: A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Clinical Outcomes, Efficacy and Safety of Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy (ATTR amyloidosis with cardiomyopathy) , HELIOS-B: Hármas fázisú, randomizált, kettősvak, placebo-kontrollált, multicentrikus vizsgálat a Vutrisiran hatásosságának és biztonságosságának kiértékelése céljából cardiomyopathiával társult transthyretin amyloidosisban szenvedő betegeknél (ATTR amyloidosis cardiomyopathiával)., HELIOS-B: Hármas fázisú, randomizált, kettősvak, placebo-kontrollált, multicentrikus vizsgálat a Vutrisiran hatásosságának és biztonságosságának kiértékelése céljából cardiomyopathiával társult transthyretin amyloidosisban szenvedő betegeknél (ATTR amyloidosis cardiomyopathiával)., HELIOS-B: Estudio de fase 3, aleatorizado, doble ciego, controlado con placebo y multicéntrico para evaluar la eficacia y la seguridad de vutrisirán en pacientes con amiloidosis cardiaca por transtiretina (amiloidosis por ATTR con miocardiopatía)., HELIOS-B: randomizirano, dvostruko slijepo, placebom kontrolirano, multicentrično ispitivanje 3. faze za procjenu učinkovitosti i sigurnosti vutirisirana u ispitanika s transtiretinskom amiloidozom s kardiomiopatijom (ATTR-amiloidoza s kardiomiopatijom), Randomizirano, dvostruko slijepo, placebom kontrolirano, multicentrično ispitivanje 3. faze za procjenu učinkovitosti i sigurnosti vutrisirana u ispitanika s transtiretinskom amiloidozom s kardiomiopatijom (ATTR-amiloidoza s kardiomiopatijom), HELIOS-B: Randomizované, dvojitě zaslepené, placebem kontrolované, multicentrické klinické hodnocení fáze 3 hodnotící účinnost a bezpečnost Vutrisiranu u pacientů s transthyretinovou amyloidózou a kardiomyopatií (ATTR amyloidóza s kardiomyopatií) , HELIOS-B: Studio di fase 3, randomizzato, in doppio cieco, controllato con placebo, multicentrico volto a valutare l’efficacia e la sicurezza di vutrisiran in pazienti con amiloidosi da transtiretina con cardiomiopatia (amiloidosi ATTR con cardiomiopatia) | |
| 2019-001458-24 | APOLLO-B: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Patisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy (ATTR Amyloidosis with Cardiomyopathy), APOLLO-B: Randomizované, dvojitě zaslepené, placebem kontrolované, multicentrické klinické hodnocení fáze 3 hodnotící účinnost a bezpečnost patisiranu u pacientů s transthyretinovou amyloidózou a kardiomyopatií (ATTR amyloidóza s kardiomyopatií), APOLLO-B: Randomizované, dvojitě zaslepené, placebem kontrolované, multicentrické klinické hodnocení fáze 3 hodnotící účinnost a bezpečnost patisiranu u pacientů s transthyretinovou amyloidózou a kardiomyopatií (ATTR amyloidóza s kardiomyopatií), APOLLO-B: Randomizované, dvojitě zaslepené, placebem kontrolované, multicentrické klinické hodnocení fáze 3 hodnotící účinnost a bezpečnost patisiranu u pacientů s transthyretinovou amyloidózou a kardiomyopatií (ATTR amyloidóza s kardiomyopatií), APOLLO-B: Randomizované, dvojitě zaslepené, placebem kontrolované, multicentrické klinické hodnocení fáze 3 hodnotící účinnost a bezpečnost patisiranu u pacientů s transthyretinovou amyloidózou a kardiomyopatií (ATTR amyloidóza s kardiomyopatií), APOLLO-B: Randomizované, dvojitě zaslepené, placebem kontrolované, multicentrické klinické hodnocení fáze 3 hodnotící účinnost a bezpečnost patisiranu u pacientů s transthyretinovou amyloidózou a kardiomyopatií (ATTR amyloidóza s kardiomyopatií), APOLLO-B: Studio di fase 3, randomizzato, in doppio cieco, controllato con placebo, multicentrico per valutare l'efficacia e la sicurezza di Patisiran in pazienti con amiloidosi da transtiretina con cardiomiopatia (amiloidosi ATTR con cardiomiopatia) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- 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.
- 2. Willingness to adhere to vitamin A supplementation per protocol.
- 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 7
- 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.
- 2. Future or current participation in another investigational device or drug study, scheduled to occur during this study.
- 3. Requires treatment with or is unwilling to avoid any concurrent treatment with non-dihydropyridine calcium channel blockers (eg, verapamil, diltiazem).
- 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.
- 5. Is not willing to comply with the contraceptive requirements during the study period.
- 6. Female patient is pregnant, planning a pregnancy, or breast-feeding.
- 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 and secondary outcome measures (English text)
Primary endpoints 1
- Frequency of adverse events
Secondary endpoints 5
- Change from baseline in KCCQ-OS score
- Change from baseline in NYHA class
- Change from baseline in cardiac biomarkers (NT-proBNP and troponin I)
- All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits)
- Change from baseline in serum TTR level
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Amvuttra 25 mg solution for injection in pre-filled syringe
PRD9937020 · Product
- Active substance
- Vutrisiran
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS USE
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 325 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- N07XX — OTHER NERVOUS SYSTEM DRUGS
- Marketing authorisation
- EU/1/22/1681/001
- MA holder
- ALNYLAM NETHERLANDS B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/18/2026
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Alnylam Pharmaceuticals Inc.
- Sponsor organisation
- Alnylam Pharmaceuticals Inc.
- Address
- 300 3rd Street
- City
- Cambridge
- Postcode
- 02142-1103
- Country
- United States
Scientific contact point
- Organisation
- Alnylam Pharmaceuticals Inc.
- Contact name
- Clinical Trials Information Line
Public contact point
- Organisation
- Alnylam Pharmaceuticals Inc.
- Contact name
- Clinical Trials Information Line
Third parties 9
| Organisation | City, country | Duties |
|---|---|---|
| Advanced Clinical LLC ORG-100047708
|
Deerfield, United States | Data management, E-data capture |
| PPD Development LP ORG-100011560
|
Wilmington, United States | On site monitoring, Code 12, Code 13, Other, Code 2, Laboratory analysis, Code 5, Code 8 |
| Fisher Clinical Services Inc. ORG-100014726
|
Mount Prospect, United States | Code 14 |
| Suvoda LLC ORG-100043523
|
Conshohocken, United States | Interactive response technologies (IRT) |
| EPL Pathology Archives LLC ORG-100042096
|
Leesburg, United States | Laboratory analysis |
| PPD Global Central Labs ORG-100046496
|
Zaventem, Belgium | Laboratory analysis |
| Fisher Clinical Services GmbH ORG-100012942
|
Allschwil, Switzerland | Code 14 |
| Gray Consulting Inc. ORG-100044159
|
Philadelphia, United States | Other |
| Charles River Laboratories Montreal ULC ORG-100041009
|
Senneville, Canada | Laboratory analysis |
Locations
11 EU/EEA countries · 40 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruitment ended | 9 | 2 |
| Belgium | Ongoing, recruitment ended | 19 | 8 |
| Czechia | Ongoing, recruitment ended | 11 | 3 |
| Denmark | Ongoing, recruitment ended | 24 | 3 |
| France | Ongoing, recruitment ended | 30 | 5 |
| Italy | Ongoing, recruitment ended | 9 | 3 |
| Netherlands | Ongoing, recruitment ended | 20 | 3 |
| Norway | Ongoing, recruitment ended | 11 | 1 |
| Portugal | Ongoing, recruitment ended | 16 | 4 |
| Spain | Ongoing, recruitment ended | 44 | 5 |
| Sweden | Ongoing, recruitment ended | 15 | 3 |
| Rest of world
Argentina, Taiwan, United Kingdom, United States, Brazil
|
— | 526 | — |
Investigational sites
Stadt Wien Wiener Gesundheitsverbund
Karl Landsteiner Institute for Cardiovascular and Critical Care Research, Bruenner Strasse 68, Floridsdorf, Vienna
Medical University Of Vienna
Internal Medicine II - Division for Cardiology, Waehringer Guertel 18-20, Alsergrund, Vienna
Jessa Ziekenhuis
Cardiology, Stadsomvaart 11, 3500, Hasselt
Universitair Ziekenhuis Gent
Cardiology, Corneel Heymanslaan 10, 9000, Gent
Hopital Erasme
Cardiology, Lennikse Baan 808, 1070, Anderlecht
Onze-Lieve-Vrouwziekenhuis
Cardiology, Moorselbaan 164, 9300, Aalst
Algemeen Ziekenhuis Delta
Cardiology, Deltalaan 1, 8800, Roeselare
O.L.Vrouw van Troost
Cardiology, Kroonveldlaan 50, 9200, Dendermonde
Centre Hospitalier Regional De La Citadelle
Cardiology, Boulevard Du Douzieme De Ligne 1, 4000, Liege
UZ Leuven
Cardiology, Herestraat 49, 3000, Leuven
Institute For Clinical And Experimental Medicine
Klinika kardiologie, Videnska 1958/9 Krc, 140 00, Prague
Synexus Czech s.r.o.
n/a, Karlovo Namesti 2097/10, Nove Mesto, Prague
Vseobecna Fakultni Nemocnice V Praze
Interní klinika - klinika kardiologie a angiologie, U Nemocnice 499/2, Nove Mesto, Prague
Region Midtjylland
Klinisk forskningsenhed, Hjertesygdomme (department of cardiology), Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
Odense University Hospital
Kardiologisk Forskningsenhed, J B Winsloews Vej 4, 5000, Odense C
Rigshospitalet
Cardiology, Blegdamsvej 9, 2100, Copenhagen Oe
Assistance Publique Hopitaux De Paris
Département de Cardiologie, 46 Rue Henri Huchard, 75877, Paris Cedex 18
Centre Hospitalier Universitaire De Toulouse
Service de Cardiologie, 1 Avenue Du Professeur Jean Poulhes, Tsa 50032, Toulouse Cedex 9
Assistance Publique Hopitaux De Paris
Département de Cardiologie, 51 Avenue Du Mal De Lattre De Tassigny, 94010, Creteil Cedex
Centre Hospitalier Universitaire De Rennes
Service de Cardiologie et Maladie Vasculaires, 2 Rue Henri Le Guilloux, 35000, Rennes
Centre Hospitalier Regional De Marseille
Service de Cardiologie, 264 Rue Saint Pierre, 13005, Marseille
Careggi University Hospital
Centro di Riferimento regionale per lo studio di Amiloidosi - SOD Medicina Sperimentale e Clinica, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Fondazione IRCCS Policlinico San Matteo
U.O.C. Med. Gen. 2 - Centro Amiloidosi Sistemiche Malattie ad Alta Complessità - S.S. Malattie Rare, Viale Camillo Golgi 19, 27100, Pavia
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
U.O. Cardiologia, Via Pietro Albertoni 15, 40138, Bologna
Universitair Medisch Centrum Groningen
Cardiology, Hanzeplein 1, 9713 GZ, Groningen
Universitair Medisch Centrum Utrecht
Cardiology, Heidelberglaan 100, 3584 CX, Utrecht
Academisch Ziekenhuis Maastricht
Cardiology, P Debyelaan 25, 6229 HX, Maastricht
Unidade Local De Saude De Santo Antonio E.P.E.
Cardiology, Largo Professor Abel Salazar, 4050-011, Porto
Unidade Local De Saude De Viseu Dao-Lafoes E.P.E.
Cardiology, Avenida Rei Dom Duarte, 3504-509, Viseu
Unidade Local De Saude Do Alto Ave E.P.E.
Cardiology, Rua Dos Cuteleiros De Guimaraes, 4835-044, Guimaraes
Unidade Local De Saude De Santa Maria E.P.E.
Cardiology, Avenida Professor Egas Moniz, 1649-035, Lisbon
Hospital Universitario Puerta De Hierro De Majadahonda
Cardiology Department, Calle De Manuel De Falla 1, 28222, Majadahonda
Hospital Universitario Virgen De La Victoria
Cardiology Department, Calle Del Arroyo Teatinos S/N, 29010, Malaga
Bellvitge University Hospital
Cardiology Department, Carrer De La Feixa Llarga S/N, 08907, L'Hospitalet De Llobregat
Hospital Universitari Vall D Hebron
Internal Medicine Department, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital Universitario Basurto
Cardiolog Department, Montevideo Etorbidea 16-18, 48013, Bilbao
Region Vaesterbotten
Kliniskt Forskningscentrum, Koksvagen 11, Alidhem, Umea
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Kardiologens Forskningsenhet, Bla Straket 5, Goteborgs Annedal, Goteborg
Karolinska University Hospital
ME Kardiologi, Tema Hjärta Kärl, Eugeniavagen 3, 171 64, Solna
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2025-11-18 | 2025-11-18 | 2026-02-10 | ||
| Belgium | 2025-03-27 | 2025-04-14 | 2026-03-06 | ||
| Czechia | 2025-03-03 | 2025-03-18 | 2026-02-13 | ||
| Denmark | 2025-02-12 | 2025-02-21 | 2026-02-23 | ||
| France | 2025-02-12 | 2025-03-07 | 2026-02-03 | ||
| Italy | 2025-02-28 | 2025-03-12 | 2025-06-05 | ||
| Netherlands | 2025-04-23 | 2025-05-02 | 2026-03-19 | ||
| Norway | 2025-07-24 | 2025-08-14 | 2026-02-27 | ||
| Portugal | 2025-03-14 | 2025-04-08 | 2026-03-18 | ||
| Spain | 2025-06-30 | 2025-07-16 | 2026-02-26 | ||
| Sweden | 2025-02-28 | 2025-03-19 | 2026-02-03 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 118 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007 Protocol Memo EU CT No discrepancy_2024-518343-38_Public | N/A |
| Protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007 Protocol_2024-518343-38_EU_EN_Pub | 1.2 |
| Protocol (for publication) | D4_Alnylam_ALN-TTRSC02-007_Patient Questionnaires_All Languages_Public | N/A |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment and Informed_Consent_Procedure_BE_Public | 4 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment and Informed_Consent_Procedure_BE_TC_NotPublic | 4 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-and-informed-consent-procedure_PT_Public | 3 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-Arrangement_NO_Public | 3 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-Arrangements_AT_Public | 3 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-Arrangements_ES_Clean_Public | 3 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-Arrangements_FR_French_Public | 3 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-Arrangements_IT_Public | 3 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-arrangements_NL_English | n/a |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-Arrangements_SE_Swedish_Public | n/a |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-Informed-Consent-Procedure_CZ | 4.0 |
| Recruitment arrangements (for publication) | K1_ALN-TTRSC02-007_Recruitment-Informed-Consent-Procedure_DNK_English | 2.0 |
| Recruitment arrangements (for publication) | K2__ALN-TTRsc02-007_Infographic_NOR_Norwegian_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRC02-007_Participant-guide_AT_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRC02-007_Participant-guide_AT_German_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRC02-007_Retention-Items_AT_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_GP-Letter_PT_English_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_AT_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_AT_German_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_BEL_Dutch_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_BEL_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_BEL_French_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_CZ_Czech_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_DNK_Danish_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_ES_Spanish_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_FR_French_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRsc02-007_Infographic_ITA_Italian_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_NL_Dutch_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_PT_Portuguese_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Infographic_SE_Swedish_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant Guide_BEL_Dutch_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant guide_BEL_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant Guide_BEL_French_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant guide_FR_French_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRsc02-007_Participant guide_ITA_Italian_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant guide_NL_Dutch_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRsc02-007_Participant Guide_NOR_Norwegian_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant guide_SE_Swedish_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant_Guide_CZ_Czech_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant-guide_ES_Spanish_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Participant-Guide_PT_Portuguese_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Patient Brochure_BEL_Dutch_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Patient Brochure_BEL_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Patient Brochure_BEL_French_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Patient Brochure_FR_French_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Patient Brochure_NL_Dutch_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Patient-Brochure_AT_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Patient-Brochure_AT_German_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Patient-Brochure_PT_Portuguese_Public | 1.0 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Retention Items_BEL_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Retention Items_ES_English_Public | n/a |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Retention Items_FR_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRsc02-007_Retention Items_ITA_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Retention Items_NL_Dutch_Public | n/a |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Retention items_NOR_English_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Retention Items_SE_Swedish_Public | 1 |
| Recruitment arrangements (for publication) | K2_ALN-TTRSC02-007_Retention-Items_CZ_English_Public | 1 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Clincierge Data Protection Notice ICF_PT_Portuguese_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Clincierge ICF_BE_Dutch_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Clincierge ICF_BE_English_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Clincierge ICF_BE_French_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Clincierge_Data-Protection-Notice_AT_German_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_GDPR-ICF_CZ_Czech_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_ICF_Main_AT_German_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_ICF_Pregnant_Partner_AT_German_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_ICF-Main_DNK_Danish_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_ICF-PP_DNK_Danish_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main ICF_BE_Dutch_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main ICF_BE_English_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main ICF_BE_French_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main ICF_NO_Norwegian_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main ICF_PT_Portuguese_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main ICF_SE_Swedish_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main-ICF_CZ_Czech_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main-ICF_ESP_spa_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main-ICF_FR_French_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Main-ICF_IT_Italian_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Memo_Replacement-of-EU-CT-number_Public | n/a |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_PP ICF_BE_Dutch_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_PP ICF_BE_English_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_PP ICF_BE_French_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_PP ICF_NO_Norwegian_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_PP ICF_SE_Swedish_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Pregnancy-and-Newborn_ICF_IT_Italian_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Pregnant Partner ICF_CZ_Czech_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Pregnant Partner ICF_PT_Portuguese_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Pregnant-Partner-ICF_ES_Spanish_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Pregnant-Partner-Participant-ICF_FR_French_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_SIS-and-ICF-adults_NL_Dutch_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_SIS-and-ICF-pregnancy-and-childs-health_NLD_nld_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Site_and_Patient_Advocacy_Contact_List_for_ICF_AT_Public | n/a |
| Subject information and informed consent form (for publication) | L1_ALN-TTRSC02-007_Sponsor Statement_Main ICF_BE_English_Public | 3.0 |
| Subject information and informed consent form (for publication) | L2_ ALN-TTRSC02-007_Subject-Questionnaire_CZ_Czech_NtF_Public | 1.0 |
| Subject information and informed consent form (for publication) | L2_ALN-TTRSC02-007_Clincierge ICF_SE_Swedish_Public | 1.0 |
| Subject information and informed consent form (for publication) | L2_ALN-TTRSC02-007_Clincierge Pay Portal Guide_PT_Portuguese_Public | 1.0 |
| Subject information and informed consent form (for publication) | L2_ALN-TTRSC02-007_Clincierge Travel Policy_PT_Portuguese_Public | 1.0 |
| Subject information and informed consent form (for publication) | L2_ALN-TTRSC02-007_Clincierge Welcome Letter_PT_Portuguese_Public | 1.0 |
| Subject information and informed consent form (for publication) | L2_ALN-TTRSC02-007_KCCQ-Questionnaire_CZ_Czech_Public | N/A |
| Subject information and informed consent form (for publication) | L2_ALN-TTRSC02-007_Patient Preference Subject Questionnaire_PT_Public | n/a |
| Subject information and informed consent form (for publication) | L2_ALN-TTRSC02-007_Patient_Card_FR_French_Public | 1.0.0 |
| Subject information and informed consent form (for publication) | L2_ALN-TTRSC02-007_Patient-Card_CZ_Czech_Public | 1.0.0 |
| Subject information and informed consent form (for publication) | L2_Alnylam_ALN-TTRSC02-007_Patient Materials_EU CTR Public Placeholder_Redacted | n/a |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Alnylam_ALN-TTRSC02-007_Vutrisiran_SmPC | 1 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_BEL_DE_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_BEL_FR_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_BEL_NL_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_CZE_CZ_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_ENG_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_ESP_ES_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_FRA_FR_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_ITA_IT_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_NLD_NL_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_NOR_NO_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_PRT_PT_Public | 3.0 |
| Synopsis of the protocol (for publication) | D1_Alnylam_ALN-TTRSC02-007_Protocol Synopsis_2024-518343-38_SWE_SW_Public | 3.0 |
Application history
28 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-04 | Sweden | Acceptable 2025-01-27
|
2025-01-28 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-02-14 | Acceptable | 2025-03-20 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-02-14 | Acceptable | 2025-03-31 | |
| 4 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-02-25 | 2025-04-07 | ||
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-02-27 | Acceptable | 2025-03-27 | |
| 6 | SUBSTANTIAL MODIFICATION | SM-10 | 2025-03-05 | Acceptable | 2025-04-02 | |
| 7 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-03-06 | Acceptable | 2025-03-19 | |
| 8 | SUBSTANTIAL MODIFICATION | SM-11 | 2025-03-06 | Sweden | Acceptable | 2025-03-31 |
| 9 | SUBSTANTIAL MODIFICATION | SM-8 | 2025-03-10 | Acceptable | 2025-04-16 | |
| 10 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-03-12 | Acceptable | 2025-03-13 | |
| 11 | SUBSTANTIAL MODIFICATION | SM-9 | 2025-03-12 | Acceptable | 2025-04-08 | |
| 12 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-03-25 | Acceptable | 2025-05-07 | |
| 13 | SUBSTANTIAL MODIFICATION | SM-12 | 2025-03-26 | Acceptable | 2025-04-03 | |
| 14 | SUBSTANTIAL MODIFICATION | SM-13 | 2025-04-02 | Acceptable | 2025-06-12 | |
| 15 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-06-17 | Sweden | Acceptable | 2025-06-17 |
| 16 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-07-16 | Acceptable | 2025-07-16 | |
| 17 | SUBSTANTIAL MODIFICATION | SM-17 | 2026-02-24 | Acceptable | 2026-04-07 | |
| 18 | SUBSTANTIAL MODIFICATION | SM-21 | 2026-02-27 | Acceptable | 2026-03-24 | |
| 19 | SUBSTANTIAL MODIFICATION | SM-14 | 2026-03-02 | Acceptable | 2026-04-19 | |
| 20 | SUBSTANTIAL MODIFICATION | SM-18 | 2026-03-03 | Acceptable | 2026-03-18 | |
| 21 | SUBSTANTIAL MODIFICATION | SM-19 | 2026-03-03 | Acceptable | 2026-04-20 | |
| 22 | SUBSTANTIAL MODIFICATION | SM-16 | 2026-03-04 | Acceptable | 2026-03-25 | |
| 23 | SUBSTANTIAL MODIFICATION | SM-22 | 2026-03-05 | Acceptable | 2026-03-18 | |
| 24 | SUBSTANTIAL MODIFICATION | SM-15 | 2026-03-09 | Acceptable | 2026-04-07 | |
| 25 | SUBSTANTIAL MODIFICATION | SM-24 | 2026-03-09 | Sweden | Acceptable | 2026-04-10 |
| 26 | SUBSTANTIAL MODIFICATION | SM-23 | 2026-03-18 | Acceptable | 2026-03-26 | |
| 27 | SUBSTANTIAL MODIFICATION | SM-20 | 2026-03-25 | Acceptable | 2026-05-11 | |
| 28 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2026-05-14 | Sweden | Acceptable | 2026-05-14 |