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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-508365-33-00 | EU Trial (CTIS) Number | ||
| 2018-002098-23 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Patisiran | Drug | Patisiran will be administered by IV infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Month 9 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Alnylam Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | La Mesa | California | 91942 | United States | ||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42290201 | Derived | 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. | |
| 38512694 |
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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.
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This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints (N=77).
Participants with hATTR amyloidosis were enrolled and treated at 57 sites in Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Cyprus, France, Germany, Greece, Italy, Japan, Korea, Malaysia, Mexico, Netherlands, Portugal, Spain, Sweden, Taiwan, United Kingdom and United States. Data is reported for the 9-Month primary analysis period.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 19, 2021 | Jul 12, 2022 |
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| Vutrisiran | Drug | Vutrisiran will be administered by SC injection. |
|
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | Up to Month 18 |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Clinical Trial Site | Jacksonville | Florida | 32224 | United States |
| Clinical Trial Site | Chicago | Illinois | 60611 | United States |
| Clinical Trial Site | Fairway | Kansas | 66205 | United States |
| Clinical Trial Site | Baltimore | Maryland | 21224 | United States |
| Clinical Trial Site | Boston | Massachusetts | 02118 | United States |
| Clinical Trial Site | Rochester | Minnesota | 55902 | United States |
| Clinical Trial Site | St Louis | Missouri | 63130 | United States |
| Clinical Trial Site | New York | New York | 10032 | United States |
| Clinical Trial Site | Chapel Hill | North Carolina | 27599 | United States |
| Clinical Trial Site | Columbus | Ohio | 43210 | United States |
| Clinical Trial Site | Portland | Oregon | 97239 | United States |
| Clinical Trial Site | Philadelphia | Pennsylvania | 19104 | United States |
| Clinical Trial Site | Dallas | Texas | 75246 | United States |
| Clinical Trial Site | Buenos Aires | C1428AQK | Argentina |
| Clinical Trial Site | Northmead | New South Wales | NSW 2152 | Australia |
| Clinical Trial Site | Brisbane | Queensland | 4102 | Australia |
| Clinical Trial Site | Melbourne | Victoria | 3128 | Australia |
| Clinical Trial Site | Brussels | 1070 | Belgium |
| Clinical Trial Site | Leuven | 3000 | Belgium |
| Clinical Trial Site | Rio de Janeiro | CEP21941 | Brazil |
| Clinical Trial Site | Sofia | 1431 | Bulgaria |
| Clinical Trial Site | Montreal | H3A 2B4 | Canada |
| Clinical Trial Site | Vancouver | V5Z 1M9 | Canada |
| Clinical Trial Site | Nicosia | 2371 | Cyprus |
| Clinical Trial Site | Bordeaux | 33076 | France |
| Clinical Trial Site | Créteil | 94000 | France |
| Clinical Trial Site | Le Kremlin-Bicêtre | 94270 | France |
| Clinical Trial Site | Lille | 59037 | France |
| Clinical Trial Site | Marseille | 13005 | France |
| Clinical Trial Site | Nantes | 44093 | France |
| Clinical Trial Site | Heidelberg | 69120 | Germany |
| Clinical Trial Site | Mainz | 55131 | Germany |
| Clinical Trial Site | Münster | 48149 | Germany |
| Clinical Trial Site | Athens | 11528 | Greece |
| Clinical Trial Site | Messina | 98100 | Italy |
| Clinical Trial Site | Milan | 20133 | Italy |
| Clinical Trial Site | Pavia | 27100 | Italy |
| Clinical Trial Site | Rome | 00168 | Italy |
| Clinical Trial Site | Kumamoto | 860-8556 | Japan |
| Clinical Trial Site | Nagano | 390-8621 | Japan |
| Clinical Trial Site | Nagoya | 466-8560 | Japan |
| Clinical Trial Site | Osaka | 565-0871 | Japan |
| Clinical Trial Site | Kuala Lumpur | 59100 | Malaysia |
| Clinical Trial Site | Mexico City | Mexico City | 14080 | Mexico |
| Clinical Trial Site | Groningen | 9713 AP | Netherlands |
| Clinical Trial Site | Lisbon | 1649-035 | Portugal |
| Clinical Trial Site | Porto | 4099-001 | Portugal |
| Clinical Trial Site | Daegu | 41944 | South Korea |
| Clinical Trial Site | Seoul | 05030 | South Korea |
| Clinical Trial Site | Seoul | 06351 | South Korea |
| Clinical Trial Site | Barcelona | 08035 | Spain |
| Clinical Trial Site | Hospitalet de Llobregat (Barcelona) | 08907 | Spain |
| Clinical Trial Site | Huelva | 21005 | Spain |
| Clinical Trial Site | Madrid | 28040 | Spain |
| Clinical Trial Site | Madrid | 28222 | Spain |
| Clinical Trial Site | Valencia | 46026 | Spain |
| Clinical Trial Site | Solna | SE-171 64 | Sweden |
| Clinical Trial Site | Umeå | 907 37 | Sweden |
| Clinical Trial Site | Taipei | 100 | Taiwan |
| Clinical Trial Site | Taipei | 11217 | Taiwan |
| Clinical Trial Site | Taoyuan City | 333 | Taiwan |
| Clinical Trial Site | London | NW3 2QG | United Kingdom |
| Derived |
| Luigetti 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. |
| 37523143 | Derived | Obici 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. |
| 35875890 | Derived | 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. |
| 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. |
| COMPLETED |
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| NOT COMPLETED |
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| Randomized Treatment Extension Period |
|
Safety Population: all participants who received any amount of study drug. Data from the placebo arm of the APOLLO study (NCT01960348) is included as it will be used as an external comparator for the primary and most other efficacy endpoints. The placebo APOLLO arm did not participate in this study.
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| ID | Title | Description |
|---|---|---|
| BG000 | External Placebo Comparator (APOLLO) | Participants in the APOLLO study (NCT01960348) who received at least 1 dose of placebo. |
| BG001 | Vutrisiran + Vutrisiran (HELIOS-A) | Participants will receive vutrisiran 25 mg SC injection q3M for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. |
| BG002 | Patisiran + Vutrisiran (HELIOS-A) | Participants will receive patisiran 0.3 mg/kg IV infusion q3w for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below. | Mean | Standard Deviation | years |
| |||||||||
| Age, Continuous | Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately. | Mean | Standard Deviation | years |
| |||||||||
| Sex: Female, Male | Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below. | Count of Participants | Participants |
| ||||||||||
| Sex: Female, Male | Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately. | Count of Participants | Participants |
| ||||||||||
| Race/Ethnicity, Customized | Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below. | Count of Participants | Participants |
| ||||||||||
| Race/Ethnicity, Customized | Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately. | Count of Participants | Participants |
| ||||||||||
| Modified Neuropathy Impairment Score +7 (mNIS+7) | 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. | Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately directly below. | Mean | Standard Deviation | score on a scale |
| ||||||||
| Modified Neuropathy Impairment Score +7 (mNIS+7) | 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. | Baseline characteristics data from the external placebo arm of the APOLLO study was not summarized with the data from HELIOS-A. APOLLO placebo data was only used as an external comparator for the primary and most other efficacy endpoints. Therefore APOLLO placebo baseline characteristic data is reported separately. | Mean | Standard Deviation | score on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Month 9 |
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| Secondary | 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. | Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Month 9 |
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| Secondary | 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. | Modified Intent-to-Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants were analyzed according to the treatment to which they were randomized. | Posted | Least Squares Mean | Standard Error | m/sec | Baseline, Month 9 |
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| Secondary | 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. | Not Posted | Baseline, Month 18 | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Not Posted | Baseline, Month 18 | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Not Posted | Baseline, Month 18 | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Not Posted | Baseline, Month 18 | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Not Posted | Baseline, Month 18 | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Not Posted | Up to Month 18 | Participants |
Non-serious AEs from first dose of study drug through Month 9. SAEs from signing of informed consent through Month 9.
Adverse events are provided for the vutrisiran group and the reference comparator (patisiran) group as of the data cutoff date (10 November 2020).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vutrisiran + Vutrisiran (HELIOS-A) | Participants will receive vutrisiran 25 mg SC injection q3M for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. | 2 | 122 | 21 | 122 | 78 | 122 |
| EG001 | Patisiran + Vutrisiran (HELIOS-A) | Participants will receive patisiran 0.3 mg/kg IV infusion q3w for 18 months during the Treatment Period followed by vutrisiran SC injection q6M or q3M during the RTE Period. | 3 | 42 | 17 | 42 | 31 | 42 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Atrioventricular block complete | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiac failure chronic | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiogenic shock | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Conduction disorder | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cyclic vomiting syndrome | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Infusion site phlebitis | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Infusion related reaction | Immune system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Escherichia urinary tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Infusion site cellulitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Vestibular neuronitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Fractured sacrum | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Post procedural complication | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiovascular evaluation | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Investigation | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Endometrial neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hospitalisation | Surgical and medical procedures | MedDRA (23.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Iliac artery occlusion | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Infusion related reaction | Immune system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Vitamin A decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
It is intended that after completion of the study, the data are to be submitted for publication in a scientific journal and/or for reporting at a scientific meeting. A copy of any proposed publication (eg, manuscript, abstracts, oral/slide presentations, book chapters) based on this study, must be provided and confirmed/received at the Sponsor at least 30 days before its submission.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Alnylam Pharmaceuticals Inc. | 866-330-0326 | clinicaltrials@alnylam.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 24, 2021 | Jul 12, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D028226 | Amyloidosis, Familial |
| C567782 | Amyloidosis, Hereditary, Transthyretin-Related |
| ID | Term |
|---|---|
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000686 | Amyloidosis |
| D057165 | Proteostasis Deficiencies |
Not provided
Not provided
| ID | Term |
|---|---|
| C000606954 | patisiran |
Not provided
Not provided
Not provided
|
|
|
|
|
| Black or African American |
|
|
| Multiple |
|
|
| Other |
|
|
| Unknown |
|
|
| White |
|
|
|
| Black or African American |
|
|
| White |
|
|
| Unknown or Not Reported |
|
|
|
|
H0: No difference between vutrisiran and external placebo comparator (APOLLO): difference (vutrisiran - placebo) = 0 |
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Participants |
|
|
|