NCT04963985

The Effect of Tafamidis on Transthyretin Stabilization, Safety, Tolerability and Efficacy in Transthyretin Amyloid Polyneuropathy Patients

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Peking University Third Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal illness resulting from autosomal dominantly inherited single-point mutations on the transthyretin gene. Tafamidis is a specific stabilizer of both variant and wild-type TTR. Tafamidis binds to TTR at the thyroxine binding sites and inhibits TTR tetramer dissociation, the rate limiting step in the amyloidogenic process. The result disrupts the amyloid cascade and fibril formation and interrupts disease progression. This study provides the basis for the study of the effect of tafamidis on the stability of transthyretin and its safety, tolerance and efficacy in patients with transthyretin amyloid polyneuropathy.

Detailed description

Transthyretin amyloidosis is a protein misfolding disease with a broad spectrum of manifestations. When the peripheral nerves are affected predominately, the disease is termed transthyretin amyloid polyneuropathy (ATTR-PN). When the heart is primarily affected, the disease is called transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-PN is a fatal illness resulting from autosomal dominantly inherited single-point mutations on the transthyretin gene. Tafamidis is a specific stabilizer of both variant and wild-type TTR. Tafamidis binds to TTR at the thyroxine binding sites and inhibits TTR tetramer dissociation, the rate limiting step in the amyloidogenic process. The result disrupts the amyloid cascade and fibril formation and interrupts disease progression. In China, ATTR-PN is rare, estimated at approximately 1997 persons . In recent years, about 30-40 case reports have been published and several ATTR-PN families were reported with different TTR gene mutations from those observed in Europe. Delay in the time to diagnosis is a major obstacle to the optimal management of ATTR-PN in China, and patients will typically wait several years between the emergence of first clinical signs and receiving an accurate diagnosis. There is a critical need to raise disease awareness, to facilitate earlier diagnosis and an urgency to enable access to treatment given the significant unmet medical need in this rare and fatal disease.

Conditions

• Transthyretin Amyloidosis

Interventions

Type	Name	Description
DRUG	Tafamidis Pill	Oral

Timeline

• Start date: 2021-06-01
• Primary completion: 2022-06-01
• Completion: 2023-06-01
• First posted: 2021-07-15
• Last updated: 2021-07-15

Locations

1 site across 1 country: China