Phase 3 N=164 Randomized Treatment

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

Amyloidosis, Hereditary · Transthyretin Amyloidosis

Bottom Line

View on ClinicalTrials.gov: NCT03759379 ↗

Enrolled (actual)

164

Serious AEs

23.2%

Results posted

Aug 2022

Primary outcome: 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)] — 14.76; -2.24 score on a scale — p=<0.0000001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Patisiran (Drug); Vutrisiran (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Alnylam Pharmaceuticals
Primary completion: Nov 2020

Outcome Measures

Outcome	Result	p-value
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)]	14.76; -2.24	<0.0000001 sig
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)]	12.9; -3.3	<0.0000001 sig
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)]	-0.133; -0.001	<0.0000001 sig
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)]	—	—
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)]	—	—
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)]	—	—
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)]	—	—
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)]	—	—
SECONDARY Percent Reduction in Serum Transthyretin (TTR) Levels Through Month 18 Between the Vutrisiran Group (HELIOS-A) and the Patisiran Group (HELIOS-A)	—	—

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03759379). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.