HELIOS-A: A Phase 3 Global Study to Evaluate the Efficacy and Safety of ALN-TTRSC02 in Patients with Hereditary Transthyretin Amyloidosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alnylam Pharmaceuticals Inc., Alnylam Pharmaceuticals Inc., Alnylam Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

9 Apr 2019 → 5 Nov 2025

Decision date (initial)

2024-06-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Alnylam Pharmaceuticals

External identifiers

EU CT number

2023-508365-33-00

EudraCT number

2018-002098-23

ClinicalTrials.gov

NCT03759379

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Pharmacodynamic, Pharmacokinetic, Safety, Efficacy, Pharmacoeconomic

To determine the efficacy of ALN-TTRSC02 in patients with hATTR amyloidosis by evaluating the effect on neurologic impairment

Secondary objectives 2

1. To determine the efficacy of ALN-TTRSC02 on quality of life, gait speed, neurologic impairment, nutritional status, and disability
2. To demonstrate the non-inferiority of ALN-TTRSC02 compared to patisiran with respect to serum TTR levels

Conditions and MedDRA coding

Hereditary Transthyretin Amyloidosis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female age 18 (or age of legal consent, whichever is older) to 85 years of age
2. Have a diagnosis of hATTR amyloidosis with documented TTR mutation
3. Have a Neuropathy Impairment Score of 5 to 130 (inclusive; this criterion must be met at the Screening Visit 2)
4. Have a Polyneuropathy Disability score of ≤3b (this criterion must be met at the Screening Visit 2)
5. Have a Karnofsky Performance Status (KPS) of ≥60%
6. Patient is willing and able to comply with the study requirements and to provide written informed consent

Exclusion criteria 10

1. Has had a liver transplant or is likely, in the opinion of the Investigator, to undergo liver transplantation during the 18-month Treatment Period of the study
2. Has known other (non-hATTR) forms of amyloidosis or clinical evidence of leptomeningeal amyloidosis
3. Has a New York Heart Association heart failure classification >2
4. Has any of the following laboratory parameter assessments: a. ALT and/or AST >1.5× upper limit of normal reference range (ULN); b. Total bilirubin >ULN (>1.5 ULN in patients with Gilbert's Syndrome) c. INR >1.2 (patients on anticoagulant therapy with an INR of ≤3.5 will be allowed)
5. Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m2
6. Has known human immunodeficiency virus (HIV) infection; or evidence of acute or chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection
7. Has other known causes of sensorimotor or autonomic neuropathy (eg, autoimmune disease, monoclonal gammopathy) that the treating physician believes to be contributing to the neuropathy
8. Current or future participation in another investigational device or drug study
9. Is currently taking tafamidis, doxycycline, or tauroursodeoxycholic acid; acid; if previously on any of these agents, must have completed a 14-day wash-out prior to dosing (Day 1)
10. Is currently taking diflunisal; if previously on this agent, must have at least a 3-day washout prior to dosing (Day 1)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) of the ALN-TTRSC02 group compared to the placebo arm of the Phase 3 patisiran-LNP study (ALN-TTR02-004; APOLLO)

Secondary endpoints 2

1. Change from baseline in the following parameters of the ALN-TTRSC02 group compared to the placebo arm of the APOLLO (patisiran) study: - Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) total score - Timed 10-meter walk test (10-MWT) - mNIS+7 - Modified body mass index (mBMI) - Rasch-built Overall Disability Scale (R-ODS)
2. Percent reduction in serum TTR levels in the ALN-TTRSC02 arm compared to the within-study patisiran arm

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alnylam Pharmaceuticals Inc.

Sponsor organisation

Alnylam Pharmaceuticals Inc.

Address

300 3rd Street

City

Cambridge

Postcode

02142-1103

Country

United States

Scientific contact point

Organisation

Alnylam Pharmaceuticals Inc.

Contact name

Clinical Trial Information Line

Public contact point

Organisation

Alnylam Pharmaceuticals Inc.

Contact name

Clinical Trial Information Line

Third parties 6

Alnylam Pharmaceuticals Inc.

Sponsor organisation

Alnylam Pharmaceuticals Inc.

Address

300 3rd Street

City

Cambridge

Postcode

02142-1103

Country

United States

Alnylam Pharmaceuticals Inc.

Sponsor organisation

Alnylam Pharmaceuticals Inc.

Address

300 3rd Street

City

Cambridge

Postcode

02142-1103

Country

United States

Locations

7 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications