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

NCT06360289 | Recruiting

• 1 other identifier: ALN-TTR-NT-003
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

Hereditary Amyloidosis, Transthyretin-Related; Asymptomatic Carrier State

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

• 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

• 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

Study Arms (2)

Asymptomatic Carriers

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

Other: Standard of Care

Participants with hATTR Amyloidosis with Polyneuropathy

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

Other: Standard of Care

Interventions

Standard of Care OTHER

This is an observational study. No study drug will be administered as a part of the study, participants will be treated according to the decision of the treating physician.

Asymptomatic Carriers; Participants with hATTR Amyloidosis with Polyneuropathy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study will include asymptomatic carriers of TTR variants or symptomatic patients with hATTR amyloidosis with polyneuropathy who review and confirm their understanding of the Patient Information Sheet (PIS) provided and do not oppose participating in the study at Centre Hospitalier Universitaire (CHU) Le Kremlin-Bicêtre Assistance Publique-Hôpitaux de Paris (APHP).

You may qualify if:

• \- 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (1)

Centre Hospitalier Universitaire (CHU) Le Kremlin-Bicêtre Assistance Publique-Hôpitaux de Paris (APHP)

Paris, Île-de-France Region, 94270, France

RECRUITING

MeSH Terms

Conditions

Amyloidosis, Hereditary, Transthyretin-Related

Interventions

Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Alnylam Clinical Trial Information Line

CONTACT

1-877-ALNYLAM; clinicaltrials@alnylam.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 11, 2024
• Study Start: April 25, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)