Clinical trial NCT03759379: HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Amyloidosis, Hereditary
Transthyretin Amyloidosis
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-11-30
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.


Eligibility 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.

Primary outcomes:
measure: 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)]
timeFrame: Baseline, Month 9
Secondary outcomes:
measure: 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)]
timeFrame: Baseline, Month 9
measure: 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)]
timeFrame: Baseline, Month 9
measure: 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)]
timeFrame: Baseline, Month 18
measure: 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)]
timeFrame: Baseline, Month 18
measure: Change From Baseline in the 10-MWT at Month 18 Between the Vutrisiran Group (HELIOS-A) and the External Placebo Comparator Group [APOLLO (NCT01960348)]
timeFrame: Baseline, Month 18
measure: 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)]
timeFrame: Baseline, Month 18
measure: 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)]
timeFrame: Baseline, Month 18
measure: Percent Reduction in Serum Transthyretin (TTR) Levels Through Month 18 Between the Vutrisiran Group (HELIOS-A) and the Patisiran Group (HELIOS-A)
timeFrame: Up to Month 18
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: Aurora
country: United States
facility: Clinical Trial Site
state: Colorado
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Chapel Hill
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Columbus
country: United States
facility: Clinical Trial Site
state: Ohio
city: Portland
country: United States
facility: Clinical Trial Site
state: Oregon
city: Philadelphia
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Fort Worth
country: United States
facility: Clinical Trial Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Clinical Trial Site
city: Box Hill
country: Australia
facility: Clinical Trial Site
city: Westmead
country: Australia
facility: Clinical Trial Site
city: Woolloongabba
country: Australia
facility: Clinical Trial Site
city: Bruxelles
country: Belgium
facility: Clinical Trial Site
city: Leuven
country: Belgium
facility: Clinical Trial Site
city: Rio De Janeiro
country: Brazil
facility: Clinical Trial Site
city: Sofia
country: Bulgaria
facility: Clinical Trial Site
city: Montréal
country: Canada
facility: Clinical Trial Site
city: Vancouver
country: Canada
facility: Clinical Trial Site
city: Nicosia
country: Cyprus
facility: Clinical Trial Site
city: Bordeaux
country: France
facility: Clinical Trial Site
city: Créteil
country: France
facility: Clinical Trial Site
city: Marseille
country: France
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Mainz
country: Germany
facility: Clinical Trial Site
city: Münster
country: Germany
facility: Clinical Trial Site
city: Athens
country: Greece
facility: Clinical Trial Site
city: Messina
country: Italy
facility: Clinical Trial Site
city: Milano
country: Italy
facility: Clinical Trial Site
city: Pavia
country: Italy
facility: Clinical Trial Site
city: Rome
country: Italy
facility: Clinical Trial Site
city: Aichi
country: Japan
facility: Clinical Trial Site
city: Kumamoto
country: Japan
facility: Clinical Trial Site
city: Nagano
country: Japan
facility: Clinical Trial Site
city: Nagoya
country: Japan
facility: Clinical Trial Site
city: Osaka
country: Japan
facility: Clinical Trial Site
city: Junggu
country: Korea, Republic of
facility: Clinical Trial Site
city: Kuala Lumpur
country: Malaysia
facility: Clinical Trial Site
city: Mexico City
country: Mexico
facility: Clinical Trial Site
city: Groningen
country: Netherlands
facility: Clinical Trial Site
city: Lisboa
country: Portugal
facility: Clinical Trial Site
city: Porto
country: Portugal
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Huelva
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Valencia
country: Spain
facility: Clinical Trial Site
city: Solna
country: Sweden
facility: Clinical Trial Site
city: Umeå
country: Sweden
facility: Clinical Trial Site
city: Taipei City
country: Taiwan
facility: Clinical Trial Site
city: Taipei
country: Taiwan
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.