HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
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| ClinicalTrials.gov Identifier: NCT03759379 |
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Recruitment Status :
Recruiting
First Posted : November 30, 2018
Last Update Posted : February 17, 2020
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Sponsor:
Alnylam Pharmaceuticals
Information provided by (Responsible Party):
Alnylam Pharmaceuticals
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Amyloidosis, Hereditary Transthyretin Amyloidosis | Drug: Patisiran Drug: Vutrisiran (ALN-TTRSC02) | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 160 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | January 18, 2019 |
| Estimated Primary Completion Date : | February 2021 |
| Estimated Study Completion Date : | May 2024 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Transthyretin amyloidosis
MedlinePlus related topics:
Amyloidosis
| Arm | Intervention/treatment |
|---|---|
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Experimental: Vutrisiran (ALN-TTRSC02)
Participants will receive vutrisiran during the Treatment and Treatment Extension Periods.
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Drug: Vutrisiran (ALN-TTRSC02)
Vutrisiran will be administered by subcutaneous (SC) injection. |
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Active Comparator: Patisiran
Participants will receive patisiran during the Treatment Period and will switch to vutrisiran during the Treatment Extension Period.
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Drug: Patisiran
Patisiran will be administered by intravenous (IV) infusion. Drug: Vutrisiran (ALN-TTRSC02) Vutrisiran will be administered by subcutaneous (SC) injection. |
Primary Outcome Measures :
- Change from Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 [ Time Frame: Baseline, 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.
- Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 [ 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 minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.
Secondary Outcome Measures :
- Change from Baseline in the Timed 10-Meter Walk Test (10-MWT) at Months 9 and 18 [ Time Frame: Baseline, Months 9 and 18 ]
- Change from Baseline in the Modified Body Mass Index (mBMI) at Months 9 and 18 [ Time Frame: Baseline, Months 9 and 18 ]
- Change from Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Months 9 and 18 [ Time Frame: Baseline, 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.
- Percentage Reduction in Serum Transthyretin (TTR) Levels at Months 9 and 18 [ Time Frame: Baseline, Months 9 and 18 ]
- Frequency of All-Cause Deaths and/or All-Cause Hospitalizations Up to Month 18 [ Time Frame: Up to Month 18 ]
- Frequency of All-Cause Deaths and/or All-Cause Hospitalizations in Participants with Cardiac Involvement Up to Month 18 [ Time Frame: Up to Month 18 ]
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| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03759379
Contacts
| Contact: Alnylam Clinical Trial Information Line | 1-877-ALNYLAM | clinicaltrials@alnylam.com | |
| Contact: Alnylam Clinical Trial Information Line | 1-877-256-9526 |
Locations
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Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
| Study Director: | John Vest, MD | Alnylam Pharmaceuticals |
Additional Information:
| Responsible Party: | Alnylam Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03759379 |
| Other Study ID Numbers: |
ALN-TTRSC02-002 2018-002098-23 ( EudraCT Number ) |
| First Posted: | November 30, 2018 Key Record Dates |
| Last Update Posted: | February 17, 2020 |
| Last Verified: | February 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Amyloid Neuropathies, Familial Amyloidosis, Familial Amyloidosis Proteostasis Deficiencies Metabolic Diseases Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases |
Nervous System Diseases Amyloid Neuropathies Peripheral Nervous System Diseases Neuromuscular Diseases Genetic Diseases, Inborn Metabolism, Inborn Errors |