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

Alnylam Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Transthyretin Amyloidosis; Amyloidosis, Hereditary

Treatments: Drug: Patisiran; Drug: Vutrisiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT03759379

ALN-TTRSC02-002

2023-508365-33-00 (EU Trial (CTIS) Number)

2018-002098-23 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 164 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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164 participants in 2 patient groups

Vutrisiran + Vutrisiran (HELIOS-A)

Experimental group

Description:

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.

Treatment:

Drug: Vutrisiran

Patisiran + Vutrisiran (HELIOS-A)

Active Comparator group

Description:

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.

Treatment:

Drug: Vutrisiran

Drug: Patisiran