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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03759379




Registration number
NCT03759379
Ethics application status
Date submitted
28/11/2018
Date registered
30/11/2018
Date last updated
9/07/2020

Titles & IDs
Public title
HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
Scientific 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)
Secondary ID [1] 0 0
2018-002098-23
Secondary ID [2] 0 0
ALN-TTRSC02-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyloidosis, Hereditary 0 0
Transthyretin Amyloidosis 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Patisiran
Treatment: Drugs - Vutrisiran (ALN-TTRSC02)

Experimental: Vutrisiran (ALN-TTRSC02) - Participants will receive vutrisiran during the Treatment and Treatment Extension Periods.

Active Comparator: Patisiran - Participants will receive patisiran during the Treatment Period and will switch to vutrisiran during the Treatment Extension Period.


Treatment: Drugs: Patisiran
Patisiran will be administered by intravenous (IV) infusion.

Treatment: Drugs: Vutrisiran (ALN-TTRSC02)
Vutrisiran will be administered by subcutaneous (SC) injection.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 - The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome.
Timepoint [1] 0 0
Baseline, Month 9
Primary outcome [2] 0 0
Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at 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 minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.
Timepoint [2] 0 0
Baseline, Month 9
Secondary outcome [1] 0 0
Change from Baseline in the Timed 10-Meter Walk Test (10-MWT) at Months 9 and 18
Timepoint [1] 0 0
Baseline, Months 9 and 18
Secondary outcome [2] 0 0
Change from Baseline in the Modified Body Mass Index (mBMI) at Months 9 and 18
Timepoint [2] 0 0
Baseline, Months 9 and 18
Secondary outcome [3] 0 0
Change from Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Months 9 and 18 - The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.
Timepoint [3] 0 0
Baseline, Months 9 and 18
Secondary outcome [4] 0 0
Percentage Reduction in Serum Transthyretin (TTR) Levels at Month 18
Timepoint [4] 0 0
Month 18
Secondary outcome [5] 0 0
Composite Events of All-Cause Mortality and All-cause Hospitalizations Up to Month 18 - All-cause mortality and frequency of all-cause hospitalizations will be compared in the overall population using an Andersen-Gill model.
Timepoint [5] 0 0
Up to Month 18
Secondary outcome [6] 0 0
Change from Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at 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 minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome.
Timepoint [6] 0 0
Baseline, Month 18
Secondary outcome [7] 0 0
Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at 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 minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.
Timepoint [7] 0 0
Baseline, Month 18

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Clinical Trial Site - Box Hill
Recruitment hospital [2] 0 0
Clinical Trial Site - Westmead
Recruitment hospital [3] 0 0
Clinical Trial Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Box Hill
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment postcode(s) [3] 0 0
- Woolloongabba
Recruitment outside Australia
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United States of America
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California
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North Carolina
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South Carolina
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Texas
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Argentina
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Buenos Aires
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Belgium
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Anderlecht
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Belgium
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Leuven
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Brazil
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Rio De Janeiro
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Bulgaria
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Sofia
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Canada
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Vancouver
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Engomi
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France
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Bordeaux
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France
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Le Kremlin-Bicêtre
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France
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Lille
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France
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Nantes
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France
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Nice
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France
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Paris
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Germany
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Heidelberg
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Germany
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Mainz
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Germany
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Münster
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Greece
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Athens
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Messina
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Italy
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Milan
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Pavia
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Italy
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Rome
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Kumamoto
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Nagoya
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Japan
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Osaka
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Korea, Republic of
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Cheongju-si
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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Malaysia
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Kuala Lumpur
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Mexico
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Mexico City
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Groningen
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Lisboa
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Porto
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Barcelona
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Huelva
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Madrid
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Valencia
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Solna
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Umeå
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Taipei City
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Taipei
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Taiwan
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Taoyuan City
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alnylam Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of vutrisiran (ALN-TTRSC02)
in patients with hereditary transthyretin amyloidosis (hATTR amyloidosis). Participants will
receive vutrisiran or the reference comparator patisiran during the Treatment Period. The
Treatment Period is followed by a Treatment Extension Period during which all participants in
the patisiran group will switch to vutrisiran. This study will use the placebo arm of the
APOLLO study (NCT01960348) as an external comparator for the co-primary and most other
efficacy endpoints.
Trial website
https://clinicaltrials.gov/show/NCT03759379
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Alnylam Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications