Observational Study of Neurofilament Light Chain (NfL) as a Biomarker in Asymptomatic Carriers of the Transthyretin (TTR) Variants and Patients With Hereditary Transthyretin-mediated (hATTR) Amyloidosis With Polyneuropathy

Alnylam Pharmaceuticals

Status: Enrolling

Conditions: Hereditary Amyloidosis, Transthyretin-Related; Asymptomatic Carrier State

Treatments: Other: Standard of Care

Study type: Observational

Funder types: Industry

Identifiers

NCT06360289

ALN-TTR-NT-003

Details and patient eligibility

About

This is a single-center observational study evaluating the potential value of NfL as a biomarker for diagnosis, detection of disease onset, monitoring of disease progression, and treatment response in asymptomatic carriers of TTR variants and symptomatic hATTR amyloidosis patients with polyneuropathy.

Full description

In this study, participants' data will be extracted from their medical records or collected based on clinical and laboratory assessments during routine visits, per the site's standard of care. Blood samples collected from the participants during routine visits will also be used for analysis. The study will be conducted in two parts: Cross-Sectional part during which a single measurement of NfL levels will be performed using blood samples collected from asymptomatic carriers, and symptomatic hATTR amyloidosis patients; Longitudinal part during which measurements of NfL levels will be performed over time using blood samples (already collected from the participants during routine visits) from asymptomatic carriers and patients with symptomatic hATTR amyloidosis.

Enrollment: 500 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

- Carrier of a documented pathogenic TTR variant confirmed with genotyping with predicted disease onset within 5 years and not diagnosed with hATTR amyloidosis with polyneuropathy

OR

Confirmed diagnosis of hATTR amyloidosis with polyneuropathy with a documented TTR variant confirmed with genotyping

- Participant is able to understand the study and does not oppose participating in the study after reviewing the content of the PIS provided.

Exclusion criteria

• A known condition (other than hATTR amyloidosis) that can cause nerve damage and affect NfL levels
• Estimated glomerular filtration rate (eGFR) <45 milliliters per minute per 1.73 meters squared (mL/min/1.73 m^2)
• Currently enrolled in a clinical study for any investigational agent.

Trial design

500 participants in 2 patient groups

Asymptomatic Carriers

Description:

Participants who are asymptomatic carriers of a pathogenic TTR variant, and not diagnosed with hATTR amyloidosis with polyneuropathy will be enrolled in this cohort.

Treatment:

Other: Standard of Care

Participants with hATTR Amyloidosis with Polyneuropathy

Description:

Participants with a confirmed diagnosis of hATTR amyloidosis with polyneuropathy with a documented TTR variant will be enrolled in this cohort.

Treatment:

Other: Standard of Care