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

NCT04963985 | Unknown Phase 4

• 1 other identifier: M2020466
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Transthyretin Amyloidosis

Outcome Measures

Primary Outcomes (1)

• TTR stabilization compared with Baseline

  TTR stabilization at Week 8 compared with Baseline, as measured by a validated immunoturbidimetric assay.

  at Week 8

Secondary Outcomes (9)

• TTR stabilization

  each follow up visit after Week 8（Week 8, Week 12 and Week 24）

• TTR concentration

  at Day 1(baseline), Week 8, Week 12 and Week 24

• Neuropathy Impairment Score：NIS-LL (lower limb)

  at Day 1(baseline) and Week 24

• TQOL score and 5 domains as measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN)

  at Day 1(baseline) and Week 24

• TQOL score and 5 domains asmeasured by the Norfolk

  at Day 1(baseline) and Week 24

Study Arms (1)

Tafamidis group

EXPERIMENTAL

During the treatment period, each participant will receive 20 mg tafamidis meglumine once daily for 24 weeks.

Drug: Tafamidis Pill

Interventions

Tafamidis Pill DRUG

Oral

Tafamidis group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Age and Sex:
• Male or female participants between the ages of 18 and 80 years.
• Type of Participant and Disease Characteristics:
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures.
• Participants have amyloid documented by biopsy in accordance with institutional site standard of care (Biopsy must have been performed within 5 years of enrollment).
• Participants must have a TTR mutation that is associated with ATTR-PN. (See Section 8.2.6.3 for further details).
• Participants have peripheral and/or autonomic neuropathy with a Karnofsky Performance Status ≥50 (refer to Appendix 5).
• Stages of disease according to symptom severity-stage I.
• Informed Consent:
• Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Medical Conditions:
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Prior/Concomitant Therapy:
• Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month. The following NSAID are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethacin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac.
• Use of diflunisal, tauroursodeoxycholate, doxycycline or a TTR stabilizing agent, or other experimental interventions for familial amyloidosis within 30 days prior to the study entry and/or during study participation. Participants who are taking or who have previously taken tafamidis.
• Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer).
• Diagnostic Assessments:
• Participant has primary (light chain) or secondary amyloidosis.
• If female, participant is pregnant or breast feeding, or plans to be pregnant or breast feeding in the next 18 months.
• Participant has received prior liver or any other organ except cornea transplantation.
• Participant has no recordable sensory threshold for vibration perception in both feet, as measured by CASE IV or participant requires significant assistance with ambulation or is wheel chair bound.
• Participants with positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
• Participant has liver function test abnormalities: alanine transaminases (ALT) and/or aspartate transaminases (AST) \>2 times upper limit of normal (ULN) that in the medical judgment of the investigator are due to reduced liver function or active liver disease.
• Participants with cardiomyopathy specific TTR mutations (Val122Ile, Leu111Met, Ile68Leu).

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijin, China

RECRUITING

MeSH Terms

Conditions

Amyloidosis, Hereditary, Transthyretin-Related

Interventions

tafamidis

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2021
• First Posted: July 15, 2021
• Study Start: June 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2023
• Last Updated: July 15, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)