Amyloidosis, HereditaryPhase 3NCT03759379
HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
A Phase 3 study testing Patisiran and Vutrisiran in people with Amyloidosis, Hereditary and Transthyretin Amyloidosis, run by Alnylam Pharmaceuticals at 64 sites in 22 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Amyloidosis, Hereditary, Transthyretin Amyloidosis
- What is being tested?
- Patisiran and Vutrisiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 64 sitesin 22 countries
- Study dates
- 14 Feb 2019to 5 Nov 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
64 sites in 22 countries.
64 sites in 22 countries
United States15 sites
Clinical Trial Site
Aurora, Colorado, 80045
Clinical Trial Site
Baltimore, Maryland, 21224
Clinical Trial Site
Boston, Massachusetts, 02118
Clinical Trial Site
Chapel Hill, North Carolina, 27599
Clinical Trial Site
Chicago, Illinois, 60611
Clinical Trial Site
Columbus, Ohio, 43210
Clinical Trial Site
Dallas, Texas, 75246
Clinical Trial Site
Fairway, Kansas, 66205
Clinical Trial Site
Jacksonville, Florida, 32224
Clinical Trial Site
La Mesa, California, 91942
Clinical Trial Site
New York, New York, 10032
Clinical Trial Site
Philadelphia, Pennsylvania, 19104
Clinical Trial Site
Portland, Oregon, 97239
Clinical Trial Site
Rochester, Minnesota, 55902
Clinical Trial Site
St Louis, Missouri, 63130
France6 sites
Clinical Trial Site
Bordeaux, 33076
Clinical Trial Site
Créteil, 94000
Clinical Trial Site
Le Kremlin-Bicêtre, 94270
Clinical Trial Site
Lille, 59037
Clinical Trial Site
Marseille, 13005
Clinical Trial Site
Nantes, 44093
Spain6 sites
Clinical Trial Site
Barcelona, 08035
Clinical Trial Site
Hospitalet de Llobregat (Barcelona), 08907
Clinical Trial Site
Huelva, 21005
Clinical Trial Site
Madrid, 28040
Clinical Trial Site
Madrid, 28222
Clinical Trial Site
Valencia, 46026
Italy4 sites
Clinical Trial Site
Messina, 98100
Clinical Trial Site
Milan, 20133
Clinical Trial Site
Pavia, 27100
Clinical Trial Site
Rome, 00168
Japan4 sites
Clinical Trial Site
Kumamoto, 860-8556
Clinical Trial Site
Nagano, 390-8621
Clinical Trial Site
Nagoya, 466-8560
Clinical Trial Site
Osaka, 565-0871
Australia3 sites
Clinical Trial Site
Brisbane, Queensland, 4102
Clinical Trial Site
Melbourne, Victoria, 3128
Clinical Trial Site
Northmead, New South Wales, NSW 2152
Germany3 sites
Clinical Trial Site
Heidelberg, 69120
Clinical Trial Site
Mainz, 55131
Clinical Trial Site
Münster, 48149
South Korea3 sites
Clinical Trial Site
Daegu, 41944
Clinical Trial Site
Seoul, 05030
Clinical Trial Site
Seoul, 06351
Taiwan3 sites
Clinical Trial Site
Taipei, 100
Clinical Trial Site
Taipei, 11217
Clinical Trial Site
Taoyuan City, 333
Belgium2 sites
Clinical Trial Site
Brussels, 1070
Clinical Trial Site
Leuven, 3000
Canada2 sites
Clinical Trial Site
Montreal, H3A 2B4
Clinical Trial Site
Vancouver, V5Z 1M9
Portugal2 sites
Clinical Trial Site
Lisbon, 1649-035
Clinical Trial Site
Porto, 4099-001
Sweden2 sites
Clinical Trial Site
Solna, SE-171 64
Clinical Trial Site
Umeå, 907 37
About this study
Official title: 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.
- Conditions
- Amyloidosis, Hereditary, Transthyretin Amyloidosis
- Being tested
- Patisiran, Vutrisiran
- Medical subject headings
- Amyloidosis, Familial, Amyloidosis, Hereditary, Transthyretin-Related
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PatisiranDrug
Also called ONPATTRO, ALN-TTR02
Patisiran will be administered by IV infusion.
VutrisiranDrug
Also called ALN-TTRSC02, AMVUTTRA
Vutrisiran will be administered by SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Vutrisiran + Vutrisiran (HELIOS-A) | Experimental | 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. Receives: Drug: Vutrisiran |
| Patisiran + Vutrisiran (HELIOS-A) | Active comparator | 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. Receives: Drug: Patisiran; Drug: Vutrisiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)]
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to Month 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2018
- Study start14 Feb 2019
- Primary completion10 Nov 2020
- Study completion5 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Amyloidosis, HereditaryStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03759379
- Sponsor's protocol ID
- ALN-TTRSC02-002
- Other IDs
- 2023-508365-33-00, 2018-002098-23, 2018, 2023
- Status last verified
- Dec 2025
- First submitted
- 28 Nov 2018
- Last updated
- 12 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Cauquil C, Adams D, Gillmore J, Gonzalez-Duarte A, Mezei M, Obici L, Sekijima Y, Zhao W, Boyle K, Badri P, Sweetser M, Moffitt C, Waddington-Cruz M. Long-term efficacy and safety of vutrisiran in hereditary transthyretin amyloidosis with polyneuropathy: final analysis of the HELIOS-A randomized treatment extension. Amyloid. 2026 Jun 15:1-12. doi: 10.1080/13506129.2026.2685666. Online ahead of print.
PubMed 42290201Luigetti 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.
PubMed 38512694Obici 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.
PubMed 37523143Adams 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.
PubMed 35875890