The Effect Of Tafamidis Meglumine In Transthyretin Amyloid Polyneuropathy Patients

Study Overview
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Brief Summary
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This is a single-arm, open-label, multicenter study designed to determine the effect of tafamidis meglumine on TTR stabilization as well as tafamidis meglumine safety, tolerability and efficacy in ATTR-PN patients in China. Approximately 10-15 participants are planned to be enrolled. All enrolled participants will receive oral tafamidis meglumine 20 mg soft capsules once daily for 72 weeks (18 months).

Detailed Description
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This is a single-arm, open-label, multicenter study designed to evaluate the efficacy, safety, tolerability as well as pharmacodynamics of tafamidis meglumine in ATTR-PN participants in China. All enrolled participants will receive oral tafamidis meglumine 20 mg soft capsules once daily starting on Day 1. Clinical visitswill be scheduled at Baseline (Day 1) and at Week 4, Week 8, Week 12, Week 24, Week 48, Week 60 and Week 72. At Week 36 and Week 60 site visit, assessment of adverse events, safety related lab testings, concomitant medications and investigational product compliance will be scheduled. Every 6 weeks (do not exceed 7 weeks since last confirmation) telephone contacts will be made during visits in which no investigative site visits are scheduled for assessment of adverse events, concomitant medications and investigational product compliance (between Week 12 and 24, between Week 24 and 36, between Week 36 and 48, between Week 48 and 60, and between Week 60 and 72).

Official Title
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A SINGLE ARM, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF ORALLY ADMINISTERED TAFAMIDIS MEGLUMINE IN TRANSTHYRETIN AMYLOID POLYNEUROPATHY PARTICIPANTS IN CHINA

Conditions
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Transthyretin Amyloid Polyneuropathy (ATTR-PN)

Intervention / Treatment
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* Drug: tafamidis meglumine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants between the ages of 18 and 80 years. Participants have amyloid documented by biopsy Participants must have a TTR mutation that is associated with ATTR-PN. Participants have peripheral and/or autonomic neuropathy Stages of disease according to symptom severity-stage I. Exclusion Criteria: Other acute or chronic medical or psychiatric condition including recent or active suicidal ideation or behavior or laboratory abnormality, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs. Use of diflunisal, tauroursodeoxycholate, doxycycline, inotersen, patisiran or any other TTR stabilizing agent, or 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. Prior/Concurrent Clinical Study Experience: 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). 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 requires significant assistance with ambulation or is wheel chair bound. Participants with cardiomyopathy specific TTR mutations. Participant has other causes of sensorimotor neuropathy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tafamidis treatment arm<br>Chinese patients diagnosed with ATTR-PN treated with tafamidis 20mg once daily oral adminiistration for 72 weeks (18 months). | Drug: tafamidis meglumine<br>* Tafamidis meglumine 20 mg, once daily, oral administration, for 72 weeks (18 months).<br>* Other names: Vyndaqel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in Neuropathy Impairment Score-lower limb (NIS-LL) at week 72 | The scale score ranges from 0-80, the higher score indicates the worse outcome. | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of TEAE during the whole study |  | baseline through week 76 | 
| change from baseline in Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at week 24, week 48, and week 72 |  | baseline, week 24, week 48, week 72 | 
| change from baseline in Modified Body Mass Index (mBMI) at week 24, week 48 and week 72 | We use participant's weight, height , and albumin concentration to calculate mBMI. | baseline, week 24, week 48, week 72 | 
| Proportion of patients achieving transthyretin (TTR) stabilization at baseline, Week 8, Week 12 and Week 24, Week 48, week 72 |  | Baseline, Week 8, Week 12, Week 24, Week 48, week 72 | 
| TTR concentration at baseline, Week 8, Week 12, Week 24, Week 48 and week 72 |  | baseline, Week 8, Week 12, Week 24, Week 48, week 72 | 
| The incidence of laboratory abnormalities during the whole study |  | baseline through week 72 | 
| Incidence of ECG abnormalities during the whole study |  | baseline through week 72 | 
| change from baseline in 36-item survey form (SF-36) at Week 24, Week 48 and week 72 |  | baseline, week 24, week 48, week 72 | 
| change from baseline in EQ-5D-5L Index Score at week 24, week 48 and week 72 |  | baseline, week 24, week 48, week 72 | 
| Incidence of vital sign abnormalities during the whole study |  | baseline through week 72 | 
| Incidence of clinically significant changes on Echocardiography during the whole study |  | baseline through week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tafamidis meglumine