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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 15
- 试验地点
- 8
- 主要终点
- Change From Baseline in Neuropathy Impairment Score-lower Limb (NIS-LL) Total Score at Week 72
研究概览
简要总结
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.
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).
详细描述
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 visits will be scheduled at Baseline (Day 1) and at Week 4, Week 8, Week 12, Week 24, Week 36, 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Tafamidis treatment arm
Chinese patients diagnosed with ATTR-PN treated with tafamidis 20mg once daily oral administration for 72 weeks (18 months).
干预措施: tafamidis meglumine (Drug)
结局指标
主要结局
Change From Baseline in Neuropathy Impairment Score-lower Limb (NIS-LL) Total Score at Week 72
时间窗: Baseline, Week 72
NIS-LL: assess muscle weakness, reflexes, sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae); sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1 = decreased, or 2 = absent. Total possible NIS-LL score range 0-88, high score = more impairment. Components of muscle weakness are scored to eight levels: 0 = Normal, 1 = 25% Weak, 2 = 50% Weak, 3 = 75% Weak, 3.25 = Move against gravity, 3.5 = Movement, gravity eliminated, 3.75 = Muscle flicker, no movement, 4 = Paralysis.
次要结局
- Change From Baseline in Total Quality of Life (TQOL) of Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) at Weeks 24, 48, and 72(Baseline, Week 24, Week 48, Week 72)
- Change From Baseline in Neuropathy Impairment Score-lower Limb (NIS-LL) Total Score at Weeks 24, and 48(Baseline, Week 24, Week 48)
- Change From Baseline in Physical Component Summary and Mental Component Summary of 36-Item Short Form Survey (SF-36) at Weeks 24, 48, and 72(Baseline, Weeks 24, 48, and 72)
- Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Week 77)
- TTR Stabilization and Percentage and 95% CI of Responders in TTR Stabilization at Post Baseline Visit(Weeks 8, 12, 24, 48, and 72)
- Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72(Baseline, Weeks 4, 8, 12, 24, 36, 48, and 72)
- Number of Participants With Categorical Electrocardiogram (ECG) Data(Baseline up to Week 72)
- Number of Participants With Clinical Laboratory Abnormalities(Baseline up to Week 72)
- Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72(Baseline, Week 24, Week 48, Week 72)
- Change From Baseline in EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) Index Score at Weeks 24, 48, and 72(Baseline, Weeks 24, 48, and 72)
- Number of Participants With Categorical Vital Signs Data(Baseline up to Week 72)
- Number of Participants With Clinically Significant Echocardiography (ECHO) Value Related to Primary Diagnosis (Transthyretin Amyloidosis [ATTR]) at Baseline, Weeks 24, 48, and 72(Baseline, Weeks 24, 48, and 72)
- Transthyretin (TTR) Concentrations on Day 1 (Baseline), and at Weeks 8, 12, 24, 48, and 72(Baseline, Weeks 8, 12, 24, 48, and 72)