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

Recruiting

• Conditions: Asymptomatic Carrier State; Hereditary Amyloidosis, Transthyretin-Related
• Interventions: Other: Standard of Care

• Registration Number: NCT06360289
• Lead Sponsor: Alnylam Pharmaceuticals

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2024-04-08
• Study First Submitted QC: 2024-04-08
• Study First Posted: 2024-04-11
• Study Start: 2024-04-25
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-24
• Last Update Posted: 2025-06-25
• Primary Completion: 2027-12-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Asymptomatic Carriers	Standard of Care	Participants who are asymptomatic carriers of a pathogenic TTR variant, and not diagnosed with hATTR amyloidosis with polyneuropathy will be enrolled in this cohort.
Participants with hATTR Amyloidosis with Polyneuropathy	Standard of Care	Participants with a confirmed diagnosis of hATTR amyloidosis with polyneuropathy with a documented TTR variant will be enrolled in this cohort.

Primary Outcome Measures

Name	Time	Method
NfL Levels in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy at Baseline	Baseline
Change in NfL Levels Over Time in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy	Up to 24 months

Secondary Outcome Measures

Name	Time	Method
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	Up to 24 months
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	Baseline
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	Baseline, 24 months
Time to Onset of Active Disease in Asymptomatic Carriers of TTR Variants	Up to 24 Months
Disease Progression in Symptomatic hATTR Amyloidosis Patients with Polyneuropathy	Up to 24 Months

Trial Locations

Locations (1)

Centre Hospitalier Universitaire (CHU) Le Kremlin-Bicêtre Assistance Publique-Hôpitaux de Paris (APHP); 🇫🇷 Paris, Île-de-France, France