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 :
Active, not recruiting
First Posted : November 30, 2018
Results First Posted : August 11, 2022
Last Update Posted : May 17, 2023
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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 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Amyloidosis, Hereditary Transthyretin Amyloidosis | Drug: Patisiran Drug: Vutrisiran | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 164 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 : | February 14, 2019 |
| Actual Primary Completion Date : | November 10, 2020 |
| Estimated Study Completion Date : | October 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Transthyretin amyloidosis
MedlinePlus related topics:
Amyloidosis
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Vutrisiran
Vutrisiran will be administered by SC injection.
Other Names:
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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.
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Drug: Patisiran
Patisiran will be administered by IV infusion.
Other Names:
Drug: Vutrisiran Vutrisiran will be administered by SC injection.
Other Names:
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Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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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
Locations
Show 54 study locations
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
| Study Director: | Medical Director | Alnylam Pharmaceuticals |
Study Documents (Full-Text)
Documents provided by Alnylam Pharmaceuticals:
Documents provided by Alnylam Pharmaceuticals:
Study Protocol [PDF] February 19, 2021
Statistical Analysis Plan [PDF] August 24, 2021
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 |
| Results First Posted: | August 11, 2022 |
| Last Update Posted: | May 17, 2023 |
| Last Verified: | May 2023 |
| 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 |