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)

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.

Study Overview

• Status: Completed
• Conditions: Transthyretin Amyloidosis; Amyloidosis, Hereditary
• Intervention / Treatment: Drug: Vutrisiran; Drug: Patisiran

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428AQK
    • Clinical Trial Site
• Australia
  • New South Wales
    • Northmead, New South Wales, Australia, NSW 2152
      • Clinical Trial Site
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Clinical Trial Site
  • Victoria
    • Melbourne, Victoria, Australia, 3128
      • Clinical Trial Site
• Belgium
  • Brussels, Belgium, 1070
    • Clinical Trial Site
  • Leuven, Belgium, 3000
    • Clinical Trial Site
• Brazil
  • Rio de Janeiro, Brazil, CEP21941
    • Clinical Trial Site
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Clinical Trial Site
• Canada
  • Montreal, Canada, H3A 2B4
    • Clinical Trial Site
  • Vancouver, Canada, V5Z 1M9
    • Clinical Trial Site
• Cyprus
  • Nicosia, Cyprus, 2371
    • Clinical Trial Site
• France
  • Bordeaux, France, 33076
    • Clinical Trial Site
  • Créteil, France, 94000
    • Clinical Trial Site
  • Le Kremlin-Bicêtre, France, 94270
    • Clinical Trial Site
  • Lille, France, 59037
    • Clinical Trial Site
  • Marseille, France, 13005
    • Clinical Trial Site
  • Nantes, France, 44093
    • Clinical Trial Site
• Germany
  • Heidelberg, Germany, 69120
    • Clinical Trial Site
  • Mainz, Germany, 55131
    • Clinical Trial Site
  • Münster, Germany, 48149
    • Clinical Trial Site
• Greece
  • Athens, Greece, 11528
    • Clinical Trial Site
• Italy
  • Messina, Italy, 98100
    • Clinical Trial Site
  • Milan, Italy, 20133
    • Clinical Trial Site
  • Pavia, Italy, 27100
    • Clinical Trial Site
  • Rome, Italy, 00168
    • Clinical Trial Site
• Japan
  • Kumamoto, Japan, 860-8556
    • Clinical Trial Site
  • Nagano, Japan, 390-8621
    • Clinical Trial Site
  • Nagoya, Japan, 466-8560
    • Clinical Trial Site
  • Osaka, Japan, 565-0871
    • Clinical Trial Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Clinical Trial Site
• Mexico
  • Mexico City
    • Mexico City, Mexico City, Mexico, 14080
      • Clinical Trial Site
• Netherlands
  • Groningen, Netherlands, 9713 AP
    • Clinical Trial Site
• Portugal
  • Lisbon, Portugal, 1649-035
    • Clinical Trial Site
  • Porto, Portugal, 4099-001
    • Clinical Trial Site
• South Korea
  • Daegu, South Korea, 41944
    • Clinical Trial Site
  • Seoul, South Korea, 06351
    • Clinical Trial Site
  • Seoul, South Korea, 05030
    • Clinical Trial Site
• Spain
  • Barcelona, Spain, 08035
    • Clinical Trial Site
  • Hospitalet de Llobregat (Barcelona), Spain, 08907
    • Clinical Trial Site
  • Huelva, Spain, 21005
    • Clinical Trial Site
  • Madrid, Spain, 28040
    • Clinical Trial Site
  • Madrid, Spain, 28222
    • Clinical Trial Site
  • Valencia, Spain, 46026
    • Clinical Trial Site
• Sweden
  • Solna, Sweden, SE-171 64
    • Clinical Trial Site
  • Umeå, Sweden, 907 37
    • Clinical Trial Site
• Taiwan
  • Taipei, Taiwan, 100
    • Clinical Trial Site
  • Taipei, Taiwan, 11217
    • Clinical Trial Site
  • Taoyuan, Taiwan, 333
    • Clinical Trial Site
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Clinical Trial Site
• United States
  • California
    • La Mesa, California, United States, 91942
      • Clinical Trial Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical Trial Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Clinical Trial Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Clinical Trial Site
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Clinical Trial Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Clinical Trial Site
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Clinical Trial Site
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Clinical Trial Site
  • New York
    • New York, New York, United States, 10032
      • Clinical Trial Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Clinical Trial Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Clinical Trial Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Clinical Trial Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Clinical Trial Site
  • Texas
    • Dallas, Texas, United States, 75246
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vutrisiran + Vutrisiran (HELIOS-A); Participants 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.	Drug: Vutrisiran; Vutrisiran will be administered by SC injection.; Other Names: ALN-TTRSC02; AMVUTTRA
Active Comparator: Patisiran + Vutrisiran (HELIOS-A); Participants 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.	Drug: Vutrisiran; Vutrisiran will be administered by SC injection.; Other Names: ALN-TTRSC02; AMVUTTRA; Drug: Patisiran; Patisiran will be administered by IV infusion.; Other Names: ONPATTRO; ALN-TTR02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)]	The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome.	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)]	The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening.	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)]	The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.	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)]	The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The total score ranges from -4 (best possible quality of life) to 136 points (worst possible quality of life). A higher score indicates a worse outcome.	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)]	The 10-MWT is a measure of ambulatory ability and measures the time (in seconds) that it takes a participant to walk 10 meters (gait speed). An increase in gait speed from baseline represents improvement, and a decrease from baseline represents worsening.	Baseline, Month 18
Change From Baseline in the Modified Body Mass Index (mBMI) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]	The mBMI, which is a measure of nutritional status, is calculated as the product of body mass index (BMI) (weight in kilograms divided by the square of height in meters) and serum albumin (g/L) to reflect fluid balance, such as fluid accumulation or dehydration. A negative change from baseline indicates a better outcome.	Baseline, Month 18
Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]	The R-ODS is a patient-reported measure of level of disability on a scale of 0-48, with 0 being the worst and 48 the best (no limitations); scores are based on activities of daily living and social participation. An increase in R-ODS from baseline suggests improvement in disability, and a decrease from baseline suggests worsening of disability.	Baseline, Month 18
Percent Reduction in Serum Transthyretin (TTR) Levels Through Month 18 Between the Vutrisiran Group (HELIOS-A) and the Patisiran Group (HELIOS-A)	Serum TTR was assessed at multiple timepoints up to Month 18.	Up to Month 18

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Investigators: Study Director: Medical Director, Alnylam Pharmaceuticals

Publications and helpful links

General Publications

• Adams 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.
• 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.
• Obici 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2019
• Primary Completion (Actual): November 10, 2020
• Study Completion (Actual): November 5, 2025

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Amyloidosis, Familial; Amyloidosis, Hereditary, Transthyretin-Related; patisiran
• Other Study ID Numbers: ALN-TTRSC02-002; 2018-002098-23 (EudraCT Number); 2023-508365-33-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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.

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No