HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
HELIOS-A: A Phase 3 Global, Randomized, Open-label Study to Evaluate the Efficacy and Safety of ALN-TTRSC02 in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
3 other identifiers
interventional
164
22 countries
64
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of vutrisiran (ALN-TTRSC02) in participants with hereditary transthyretin amyloidosis (hATTR amyloidosis). Participants will receive vutrisiran subcutaneous (SC) injection once every 3 months (q3M) or the reference comparator patisiran intravenous (IV) injection once every 3 weeks (q3w) during the 18 month Treatment Period. This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints during the 18 Month Treatment Period. Following the 18 Month Treatment Period, all participants will be randomized to receive vutrisiran 50 mg SC injection once every 6 months (q6M) or vutrisiran 25 mg q3M in the Randomized Treatment Extension (RTE) Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Feb 2019
Longer than P75 for phase_3
64 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 28, 2018
CompletedFirst Posted
Study publicly available on registry
November 30, 2018
CompletedStudy Start
First participant enrolled
February 14, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 10, 2020
CompletedResults Posted
Study results publicly available
August 11, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
November 5, 2025
CompletedJanuary 12, 2026
December 1, 2025
1.7 years
November 28, 2018
July 12, 2022
December 18, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.
Baseline, Month 9
Secondary Outcomes (8)
Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
Baseline, Month 9
Change From Baseline in the Timed 10-Meter Walk Test (10-MWT) at Month 9 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
Baseline, Month 9
Change From Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
Baseline, Month 18
Change From Baseline in Norfolk QoL-DN Total Score at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
Baseline, Month 18
Change From Baseline in the 10-MWT at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
Baseline, Month 18
- +3 more secondary outcomes
Study Arms (2)
Vutrisiran + Vutrisiran (HELIOS-A)
EXPERIMENTALParticipants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran 50 mg SC injection once every 6 months (q6M) or vutrisiran 25 mg q3M during the Randomized Treatment Extension (RTE) Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.
Patisiran + Vutrisiran (HELIOS-A)
ACTIVE COMPARATORParticipants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran 50 mg SC injection once q6M or vutrisiran 25 mg q3M during the RTE Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.
Interventions
Patisiran will be administered by IV infusion.
Vutrisiran will be administered by SC injection.
Eligibility Criteria
You may qualify if:
- Male or female of 18 to 85 years of age (inclusive);
- Has a diagnosis of hATTR amyloidosis with transthyretin (TTR) mutation;
- Has adequate neurologic impairment score (NIS);
- Has adequate polyneuropathy disability (PND) score;
- Has adequate Karnofsky Performance Status (KPS).
You may not qualify if:
- Had a prior liver transplant or is likely to undergo liver transplantation during the study;
- Has known other (non-hATTR) forms of amyloidosis or leptomeningeal amyloidosis;
- Has New York Heart Association heart failure classification \>2;
- Clinically significant liver function test abnormalities;
- Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection;
- Received an experimental drug within 30 days of dosing;
- Received prior TTR-lowering treatment;
- Has other known causes of neuropathy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (64)
Clinical Trial Site
La Mesa, California, 91942, United States
Clinical Trial Site
Aurora, Colorado, 80045, United States
Clinical Trial Site
Jacksonville, Florida, 32224, United States
Clinical Trial Site
Chicago, Illinois, 60611, United States
Clinical Trial Site
Fairway, Kansas, 66205, United States
Clinical Trial Site
Baltimore, Maryland, 21224, United States
Clinical Trial Site
Boston, Massachusetts, 02118, United States
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Rochester, Minnesota, 55902, United States
Clinical Trial Site
St Louis, Missouri, 63130, United States
Clinical Trial Site
New York, New York, 10032, United States
Clinical Trial Site
Chapel Hill, North Carolina, 27599, United States
Clinical Trial Site
Columbus, Ohio, 43210, United States
Clinical Trial Site
Portland, Oregon, 97239, United States
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Philadelphia, Pennsylvania, 19104, United States
Clinical Trial Site
Dallas, Texas, 75246, United States
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Buenos Aires, C1428AQK, Argentina
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Northmead, New South Wales, NSW 2152, Australia
Clinical Trial Site
Brisbane, Queensland, 4102, Australia
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Melbourne, Victoria, 3128, Australia
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Brussels, 1070, Belgium
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Leuven, 3000, Belgium
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Rio de Janeiro, CEP21941, Brazil
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Sofia, 1431, Bulgaria
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Montreal, H3A 2B4, Canada
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Vancouver, V5Z 1M9, Canada
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Nicosia, 2371, Cyprus
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Bordeaux, 33076, France
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Créteil, 94000, France
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Le Kremlin-Bicêtre, 94270, France
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Lille, 59037, France
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Marseille, 13005, France
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Nantes, 44093, France
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Heidelberg, 69120, Germany
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Mainz, 55131, Germany
Clinical Trial Site
Münster, 48149, Germany
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Athens, 11528, Greece
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Messina, 98100, Italy
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Milan, 20133, Italy
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Pavia, 27100, Italy
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Rome, 00168, Italy
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Kumamoto, 860-8556, Japan
Clinical Trial Site
Nagano, 390-8621, Japan
Clinical Trial Site
Nagoya, 466-8560, Japan
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Osaka, 565-0871, Japan
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Kuala Lumpur, 59100, Malaysia
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Mexico City, Mexico City, 14080, Mexico
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Groningen, 9713 AP, Netherlands
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Lisbon, 1649-035, Portugal
Clinical Trial Site
Porto, 4099-001, Portugal
Clinical Trial Site
Daegu, 41944, South Korea
Clinical Trial Site
Seoul, 05030, South Korea
Clinical Trial Site
Seoul, 06351, South Korea
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Barcelona, 08035, Spain
Clinical Trial Site
Hospitalet de Llobregat (Barcelona), 08907, Spain
Clinical Trial Site
Huelva, 21005, Spain
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Madrid, 28040, Spain
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Madrid, 28222, Spain
Clinical Trial Site
Valencia, 46026, Spain
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Solna, SE-171 64, Sweden
Clinical Trial Site
Umeå, 907 37, Sweden
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Taipei, 100, Taiwan
Clinical Trial Site
Taipei, 11217, Taiwan
Clinical Trial Site
Taoyuan, 333, Taiwan
Clinical Trial Site
London, NW3 2QG, United Kingdom
Related Publications (3)
Luigetti M, Quan D, Berk JL, Conceicao I, Misumi Y, Chao CC, Bender S, Aldinc E, Vest J, Adams D. Impact of Baseline Neuropathy Severity on Vutrisiran Treatment Response in the Phase 3 HELIOS-A Study. Neurol Ther. 2024 Jun;13(3):625-639. doi: 10.1007/s40120-024-00595-9. Epub 2024 Mar 21.
PMID: 38512694DERIVEDObici L, Ajroud-Driss S, Lin KP, Berk JL, Gillmore JD, Kale P, Koike H, Danese D, Aldinc E, Chen C, Vest J, Adams D; HELIOS-A Collaborators Study Group. Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy. Neurol Ther. 2023 Oct;12(5):1759-1775. doi: 10.1007/s40120-023-00522-4. Epub 2023 Jul 31.
PMID: 37523143DERIVEDAdams D, Tournev IL, Taylor MS, Coelho T, Plante-Bordeneuve V, Berk JL, Gonzalez-Duarte A, Gillmore JD, Low SC, Sekijima Y, Obici L, Chen C, Badri P, Arum SM, Vest J, Polydefkis M; HELIOS-A Collaborators. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023 Mar;30(1):1-9. doi: 10.1080/13506129.2022.2091985. Epub 2022 Jul 23.
PMID: 35875890DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Alnylam Pharmaceuticals Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Alnylam Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 28, 2018
First Posted
November 30, 2018
Study Start
February 14, 2019
Primary Completion
November 10, 2020
Study Completion
November 5, 2025
Last Updated
January 12, 2026
Results First Posted
August 11, 2022
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
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. Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more. Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.