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

Observational Study of Neurofilament Light Chain (NfL) Levels in Asymptomatic Carriers of the TTR Gene Variants and Patients With hATTR Amyloidosis With Polyneuropathy, Including Patients Who Undergo Treatment Change - NeuroFeeL Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hereditary Amyloidosis, Transthyretin-Related; Asymptomatic Carrier State
• Intervention / Treatment: Other: Standard of Care

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 Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Alnylam Clinical Trial Information Line; Phone Number: 1-877-ALNYLAM; Email: clinicaltrials@alnylam.com

Study Locations

• France
  • Île-de-France
    • Paris, Île-de-France, France, 94270
      • Centre Hospitalier Universitaire (CHU) Le Kremlin-Bicêtre Assistance Publique-Hôpitaux de Paris (APHP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• 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).

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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.
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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neuromuscular Diseases; Peripheral Nervous System Diseases; Proteostasis Deficiencies; Metabolism, Inborn Errors; Amyloidosis; Polyneuropathies; Amyloidosis, Familial
• Other Study ID Numbers: ALN-TTR-NT-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No