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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT03759379
Registration number
NCT03759379
Ethics application status
Date submitted
28/11/2018
Date registered
30/11/2018
Titles & IDs
Public title
HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
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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)
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Secondary ID [1]
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2018-002098-23
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Secondary ID [2]
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ALN-TTRSC02-002
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Amyloidosis, Hereditary
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Transthyretin Amyloidosis
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Condition category
Condition code
Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Neurological
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Other neurological disorders
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Metabolic and Endocrine
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Other metabolic disorders
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Metabolic and Endocrine
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Metabolic disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Patisiran
Treatment: Drugs - Vutrisiran
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 SC injection once every 6 months (q6M) or q3M during the Randomized Treatment Extension (RTE) Period.
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 SC injection q6M or q3M during the RTE Period.
Treatment: Drugs: Patisiran
Patisiran will be administered by IV infusion.
Treatment: Drugs: Vutrisiran
Vutrisiran will be administered by SC injection.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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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)]
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Month 9
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Secondary outcome [1]
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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)]
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Month 9
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Secondary outcome [2]
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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)]
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline, Month 9
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Secondary outcome [3]
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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)]
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline, Month 18
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Secondary outcome [4]
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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)]
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline, Month 18
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Secondary outcome [5]
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Change From Baseline in the 10-MWT at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
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Assessment method [5]
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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.
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Timepoint [5]
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Baseline, Month 18
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Secondary outcome [6]
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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)]
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline, Month 18
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Secondary outcome [7]
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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)]
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline, Month 18
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Secondary outcome [8]
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Percent Reduction in Serum Transthyretin (TTR) Levels Through Month 18 Between the Vutrisiran Group (HELIOS-A) and the Patisiran Group (HELIOS-A)
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Assessment method [8]
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Serum TTR was assessed at multiple timepoints up to Month 18.
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Timepoint [8]
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Up to Month 18
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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).
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Minimum age
18
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Maximum age
85
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
14/02/2019
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Date of last participant enrolment
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Actual
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Date of last data collection
Anticipated
1/10/2026
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Actual
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Sample size
Target
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Accrual to date
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Final
164
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Clinical Trial Site - Box Hill
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Recruitment hospital [2]
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Clinical Trial Site - Westmead
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Recruitment hospital [3]
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Clinical Trial Site - Woolloongabba
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Recruitment postcode(s) [1]
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- Box Hill
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Recruitment postcode(s) [2]
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- Westmead
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Recruitment postcode(s) [3]
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- Woolloongabba
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Recruitment outside Australia
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United States of America
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California
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Colorado
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Funding & Sponsors
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Name
Alnylam Pharmaceuticals
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Ethics approval
Ethics application status
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Summary
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 SC injection once every 6 months (q6M) or q3M in the Randomized Treatment Extension (RTE) Period.
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Trial website
https://clinicaltrials.gov/study/NCT03759379
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Trial related presentations / 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.
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Public notes
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Contacts
Principal investigator
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Medical Director
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Alnylam Pharmaceuticals
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
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 United States (US) and/or the European Union (EU).
Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/79/NCT03759379/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/79/NCT03759379/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT03759379