HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)

Transthyretin Amyloidosis Clinical Trial

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)

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
• 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
• 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.

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis
• Amyloidosis, Familial
• Amyloidosis, Hereditary
• Transthyretin Amyloidosis

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