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 Pharmaceuticals500 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

500

Conditions

Hereditary Amyloidosis, Transthyretin-Related Asymptomatic Carrier State

Interventions

Eligibility

Sex: ALLHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

NfL Levels in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy at Baseline

Time frame: Baseline

Change in NfL Levels Over Time in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy

Time frame: Up to 24 months

Secondary Outcomes

Correlation Between the NfL Levels and Various Biological and Clinical Activity Parameters in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy at Baseline

Time frame: Baseline

Correlation Between the Change in NfL Levels and Various Biological and Clinical Activity Parameters in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy

Time frame: Up to 24 months

Comparison of the Measured NfL Levels to the Normal Levels Expected to be Seen in the General Population by Using the Existing Reference Ranges and Databases

Time frame: Baseline, 24 months

Time to Onset of Active Disease in Asymptomatic Carriers of TTR Variants

Time frame: Up to 24 Months

Disease Progression in Symptomatic hATTR Amyloidosis Patients with Polyneuropathy