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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03759379
Other study ID # ALN-TTRSC02-002
Secondary ID 2018-002098-23
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date February 14, 2019
Est. completion date October 2026

Study information

Verified date May 2024
Source Alnylam Pharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 164
Est. completion date October 2026
Est. primary completion date November 10, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years to 85 Years
Eligibility 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.

Study Design


Intervention

Drug:
Patisiran
Patisiran will be administered by IV infusion.
Vutrisiran
Vutrisiran will be administered by SC injection.

Locations

Country Name City State
Argentina Clinical Trial Site Buenos Aires
Australia Clinical Trial Site Box Hill
Australia Clinical Trial Site Westmead
Australia Clinical Trial Site Woolloongabba
Belgium Clinical Trial Site Bruxelles
Belgium Clinical Trial Site Leuven
Brazil Clinical Trial Site Rio De Janeiro
Bulgaria Clinical Trial Site Sofia
Canada Clinical Trial Site Montréal
Canada Clinical Trial Site Vancouver
Cyprus Clinical Trial Site Nicosia
France Clinical Trial Site Bordeaux
France Clinical Trial Site Créteil
France Clinical Trial Site Marseille
France Clinical Trial Site Paris
Germany Clinical Trial Site Mainz
Germany Clinical Trial Site Münster
Greece Clinical Trial Site Athens
Italy Clinical Trial Site Messina
Italy Clinical Trial Site Pavia
Italy Clinical Trial Site Rome
Japan Clinical Trial Site Kumamoto
Japan Clinical Trial Site Nagano
Japan Clinical Trial Site Nagoya
Japan Clinical Trial Site Osaka
Korea, Republic of Clinical Trial Site Junggu
Malaysia Clinical Trial Site Kuala Lumpur
Mexico Clinical Trial Site Mexico City
Netherlands Clinical Trial Site Groningen
Portugal Clinical Trial Site Lisboa
Portugal Clinical Trial Site Porto
Spain Clinical Trial Site Barcelona
Spain Clinical Trial Site Huelva
Spain Clinical Trial Site Madrid
Spain Clinical Trial Site Valencia
Sweden Clinical Trial Site Solna
Sweden Clinical Trial Site Umeå
Taiwan Clinical Trial Site Taipei
Taiwan Clinical Trial Site Taipei City
United Kingdom Clinical Trial Site London
United States Clinical Trial Site Aurora Colorado
United States Clinical Trial Site Baltimore Maryland
United States Clinical Trial Site Boston Massachusetts
United States Clinical Trial Site Chapel Hill North Carolina
United States Clinical Trial Site Chicago Illinois
United States Clinical Trial Site Columbus Ohio
United States Clinical Trial Site Fort Worth Texas
United States Clinical Trial Site New York New York
United States Clinical Trial Site Philadelphia Pennsylvania
United States Clinical Trial Site Portland Oregon
United States Clinical Trial Site Rochester Minnesota
United States Clinical Trial Site Saint Louis Missouri
United States Clinical Trial Site San Diego California

Sponsors (1)

Lead Sponsor Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Cyprus,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Portugal,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
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. Baseline, Month 9
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. Baseline, Month 9
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. Baseline, Month 9
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. Baseline, Month 18
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. Baseline, Month 18
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. Baseline, Month 18
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. Baseline, Month 18
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. Baseline, Month 18
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. Up to Month 18
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