HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)

December 18, 2025 updated by: Alnylam Pharmaceuticals

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
164

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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)]
Time Frame: Baseline, Month 9
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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)]
Time Frame: Baseline, Month 9
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)]
Time Frame: Baseline, Month 9
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)]
Time Frame: Baseline, Month 18
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)]
Time Frame: Baseline, Month 18
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)]
Time Frame: Baseline, Month 18
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)]
Time Frame: Baseline, Month 18
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)]
Time Frame: Baseline, Month 18
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)
Time Frame: Up to Month 18
Serum TTR was assessed at multiple timepoints up to Month 18.
Up to Month 18

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alnylam Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Alnylam Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 14, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 10, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 5, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 28, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 28, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 30, 2018

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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