Clinical trial NCT06360289: 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
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hereditary Amyloidosis, Transthyretin-Related
Asymptomatic Carrier State
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-04-11
Enrollment: 500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: NfL Levels in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy at Baseline
timeFrame: Baseline
measure: Change in NfL Levels Over Time in Asymptomatic Carriers of a TTR Variant and Symptomatic hATTR Patients With Polyneuropathy
timeFrame: Up to 24 months
Secondary outcomes:
measure: 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
timeFrame: Baseline
measure: 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
timeFrame: Up to 24 months
measure: 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
timeFrame: Baseline, 24 months
measure: Time to Onset of Active Disease in Asymptomatic Carriers of TTR Variants
timeFrame: Up to 24 Months
measure: Disease Progression in Symptomatic hATTR Amyloidosis Patients with Polyneuropathy
timeFrame: Up to 24 Months
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre Hospitalier Universitaire (CHU) Le Kremlin-Bicêtre Assistance Publique-Hôpitaux de Paris (APHP)
state: Île-de-France
Study officials:
References: