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HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy

Primary Purpose

Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Vutrisiran
Sterile Normal Saline (0.9% NaCl)
Sponsored by
Alnylam Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transthyretin Amyloidosis (ATTR) With Cardiomyopathy focused on measuring ATTR, Cardiomyopathy, Amyloidosis, TTR, Transthyretin, TTR-mediated amyloidosis, Amyloidosis, Hereditary, Amyloidosis, Hereditary, Transthyretin-Related, Familial Amyloidosis, RNAi therapeutic, Transthyretin amyloid cardiomyopathy, TTR cardiomyopathy, ATTR-CM, Wild-type TTR, V122I, TTR amyloidosis, Amyloidosis, Wild Type

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Has a documented diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as either hereditary ATTR (hATTR) amyloidosis with cardiomyopathy or wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy meeting pre-specified diagnostic criteria
  • Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF OR clinical evidence of HF

Exclusion Criteria:

  • Has known primary amyloidosis or leptomeningeal amyloidosis
  • Has New York Heart Association (NYHA) Class IV heart failure
  • Has NYHA Class III heart failure AND is at high risk based on pre-specified criteria
  • Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV at the Screening visit
  • Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2
  • Has received prior TTR-lowering treatment
  • Has other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Vutrisiran 25 mg

Placebo

Arm Description

Participants will receive vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) during the double-blind period.

Participants will receive placebo during the double-blind period.

Outcomes

Primary Outcome Measures

Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits)
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model.

Secondary Outcome Measures

Change from Baseline in 6-Minute Walk Test (6-MWT) at Month 30
Change from Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) at Month 30
The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary [OS]). Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
Change from Baseline in Mean Left Ventricular (LV) Wall Thickness by Echocardiographic Assessment at Month 30
Change from Baseline in Global Longitudinal Strain by Echocardiographic Assessment at Month 30
Composite Endpoint of All-Cause Mortality and Recurrent All-cause Hospitalizations and Urgent HF Visits
All-cause mortality and recurrent all-cause hospitalizations and urgent HF visits will be compared between treatment groups using an Andersen-Gill model.
All-cause Mortality
Rate of Recurrent CV Events (CV Hospitalizations and Urgent HF Visits)
Change from Baseline in N-terminal prohormone B-type Natriuretic Peptide (NTproBNP) at Month 30

Full Information

First Posted
November 4, 2019
Last Updated
October 20, 2023
Sponsor
Alnylam Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04153149
Brief Title
HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Official Title
HELIOS-B: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 26, 2019 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alnylam Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This study will evaluate the efficacy and safety of vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) compared to placebo in patients with ATTR amyloidosis with cardiomyopathy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Keywords
ATTR, Cardiomyopathy, Amyloidosis, TTR, Transthyretin, TTR-mediated amyloidosis, Amyloidosis, Hereditary, Amyloidosis, Hereditary, Transthyretin-Related, Familial Amyloidosis, RNAi therapeutic, Transthyretin amyloid cardiomyopathy, TTR cardiomyopathy, ATTR-CM, Wild-type TTR, V122I, TTR amyloidosis, Amyloidosis, Wild Type

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
655 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vutrisiran 25 mg
Arm Type
Experimental
Arm Description
Participants will receive vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) during the double-blind period.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo during the double-blind period.
Intervention Type
Drug
Intervention Name(s)
Vutrisiran
Other Intervention Name(s)
ALN-TTRSC02
Intervention Description
Vutrisiran 25 mg will be administered by SC injection q3M.
Intervention Type
Drug
Intervention Name(s)
Sterile Normal Saline (0.9% NaCl)
Intervention Description
Sterile normal saline (0.9% NaCl) will be administered by SC injection q3M.
Primary Outcome Measure Information:
Title
Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits)
Description
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model.
Time Frame
30-36 months
Secondary Outcome Measure Information:
Title
Change from Baseline in 6-Minute Walk Test (6-MWT) at Month 30
Time Frame
Baseline, Month 30
Title
Change from Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) at Month 30
Description
The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary [OS]). Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
Time Frame
Baseline, Month 30
Title
Change from Baseline in Mean Left Ventricular (LV) Wall Thickness by Echocardiographic Assessment at Month 30
Time Frame
Baseline, Month 30
Title
Change from Baseline in Global Longitudinal Strain by Echocardiographic Assessment at Month 30
Time Frame
Baseline and Month 30
Title
Composite Endpoint of All-Cause Mortality and Recurrent All-cause Hospitalizations and Urgent HF Visits
Description
All-cause mortality and recurrent all-cause hospitalizations and urgent HF visits will be compared between treatment groups using an Andersen-Gill model.
Time Frame
30-36 months
Title
All-cause Mortality
Time Frame
30-36 months
Title
Rate of Recurrent CV Events (CV Hospitalizations and Urgent HF Visits)
Time Frame
30-36 months
Title
Change from Baseline in N-terminal prohormone B-type Natriuretic Peptide (NTproBNP) at Month 30
Time Frame
Baseline, Month 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Has a documented diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as either hereditary ATTR (hATTR) amyloidosis with cardiomyopathy or wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy meeting pre-specified diagnostic criteria Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF OR clinical evidence of HF Exclusion Criteria: Has known primary amyloidosis or leptomeningeal amyloidosis Has New York Heart Association (NYHA) Class IV heart failure Has NYHA Class III heart failure AND is at high risk based on pre-specified criteria Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV at the Screening visit Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 Has received prior TTR-lowering treatment Has other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Alnylam Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Clinical Trial Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Clinical Trial Site
City
Gainesville
State/Province
Georgia
ZIP/Postal Code
30501
Country
United States
Facility Name
Clinical Trial Site
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Clinical Trial Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
Clinical Trial Site
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Clinical Trial Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Clinical Trial Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Clinical Trial Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Clinical Trial Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
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United States
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Houston
State/Province
Texas
ZIP/Postal Code
77030
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United States
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Buenos Aires
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Argentina
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Adelaide
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Australia
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Melbourne
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Australia
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Sydney
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Australia
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Westmead
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Australia
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Woolloongabba
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Australia
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Vienna
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Austria
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Anderlecht
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Belgium
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Dendermonde
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Belgium
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Ghent
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Belgium
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Leuven
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Belgium
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Quebec City
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Canada
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Toronto
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Canada
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Zagreb
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Croatia
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Olomouc
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Czechia
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Prague
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Czechia
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Aarhus
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Denmark
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Odense
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Denmark
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Créteil
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France
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Marseille
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France
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Paris
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France
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Toulouse
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France
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Essen
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Germany
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Göttingen
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Germany
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Heidelberg
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Germany
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Leipzig
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Germany
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Münster
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Germany
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Würzburg
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Germany
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Budapest
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Hungary
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Dublin
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Ireland
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Haifa
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Israel
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Aichi
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Japan
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Fukuoka
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Japan
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Kagawa
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Japan
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Kashihara
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Japan
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Kumamoto
Country
Japan
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Matsumoto
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Japan
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Nankoku
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Japan
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Osaka
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Japan
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Tokyo
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Japan
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Seoul
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Korea, Republic of
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Riga
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Latvia
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Kaunas
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Lithuania
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Groningen
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Netherlands
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Utrecht
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Netherlands
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Oslo
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Norway
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Lima
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Peru
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San Miguel
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Peru
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Gdańsk
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Poland
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Wrocław
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Poland
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Guimarães
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Portugal
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Lisboa
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Portugal
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Porto
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Portugal
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Barcelona
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Spain
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Bilbao
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Spain
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Huelva
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Gothenburg
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Sweden
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Umeå
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Sweden
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Birmingham
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United Kingdom
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Cardiff
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United Kingdom
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Glasgow
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Clinical Trial Site
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Middlesbrough
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy

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