This is a national, multi-center, single-arm study, open-label to patients with symptomatic Transthyretin amyloid cardiomyopathy (ATTR-CM) who are tafamidis naïve. This study is to obtain safety, descriptive efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) data for tafamidis orally once daily. Subject eligibility for participation in the study will receive tafamidis once daily or 12 months following the assessment as the screening and baseline, month 1, 3, 6, 9 and 12 visits (or Early Study Discontinuation).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
61 mg, once daily, oral administration, for 12 months.
Peking University First Hospital
Beijing, Beijing Municipality, China
Peking University Third Hospital
Beijing, Beijing Municipality, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Wuhan, Hubei, China
The Second Xiangya Hospital of Central South University
Changsha, Hunan, China
The First Affiliated Hospital of Dalian Medical University
Dalian, Liaoning, China
West China Hospital of Sichuan University
Chengdu, Sichuan, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, China
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. All AEs that started after the first dosing but before the last dose plus the lag time (28 days) were TEAEs. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent disability/incapacity; congenital anomaly/birth defect. A severe TEAE was an event that prevented normal everyday activities. Severe TEAEs were assessed by the investigator.
Time frame: From first dose of study intervention on Day 1 (baseline) up to 28 days post the last dose of study intervention (up to a maximum of 393 days)
Number of Participants With Treatment-Related TEAEs
An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. All AEs that started after the first dosing but before the last dose plus the lag time (28 days) were TEAEs. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent disability/incapacity; congenital anomaly/birth defect. A severe TEAE was an event that prevented normal everyday activities. Severe TEAEs and treatment-related TEAEs were assessed by the investigator.
Time frame: From first dose of study intervention on Day 1 (baseline) up to 28 days post the last dose of study intervention (up to a maximum of 393 days)
Change From Baseline (CFB) for Distance Walked During 6 Minute Walk Test (6MWT) at Months 6 and 12
As a measure of functional capacity, the 6MWT measured the distance a participant could walk on a straight course in 6 minutes. 6MWT was conducted in accordance with guidelines established by the American Thoracic Society at Month 6 and Month 12 visits. Baseline was defined as the last measurement prior to first dose of study intervention.
Time frame: Baseline, months 6 and 12
Change From Baseline for N Terminal Prohormone B Type Natriuretic Peptide (NT-proBNP) at Months 6 and 12
Plasma NT-proBNP is a guideline-mandated biomarker in heart failure. Baseline was defined as the last measurement prior to the first dose of study treatment.
Time frame: Baseline, months 6 and 12
Percentage of Responders in Transthyretin (TTR) Stabilization Post Dose at Months 1, 6, and 12
Blood sample of approximate 10 mL was collected at baseline, Months 1, 6, and 12 visits for measurement of TTR and TTR tetramer concentrations. TTR concentration was obtained prior to urea denaturation and TTR tetramer concentration was obtained after urea denaturation. Month 1 visit occurred 1 month post Day 1 +/- 1 week, Month 6 visit occurred 6 months post Day 1 +/- 2 weeks, and Month 12 visit occurred 12 months post Day 1 +/- 2 weeks or within 2 weeks after end of treatment. Responder was the participant who achieved TTR stabilization (ie, who had been TTR stabilized). Declaring a participant to have been (TTR) 'stabilized' was defined as the participant whose percent stabilization was equal to or greater than 32%. Percent stabilization (%) was calculated as (\[fraction of initial {FOI} dosed - FOI baseline\] / FOI baseline)×100, and FOI was calculated as average TTR tetramer concentration (post-denaturation) / average TTR concentration (pre-denaturation).
Time frame: Predose on Day 1 (baseline), predose and 3 hours post dose at Month 1 visit, 7 hours post dose at Month 6 visit, and 1 hour post dose at Month 12 visit
TTR Concentration at Baseline, Months 1, 6, and 12
One K2EDTA blood sample of approximate 10 mL was collected on Day 1 (baseline), and at Months 1, 6, and 12 visits for measurement of TTR concentration. Month 1 visit occurred 1 month post Day 1 +/- 1 week, Month 6 visit occurred 6 months post Day 1 +/- 2 weeks, and Month 12 visit occurred 12 months post Day 1 +/- 2 weeks or within 2 weeks after end of treatment.
Time frame: Predose on Day 1 (baseline), predose and 3 hours post dose at Month 1 visit, 7 hours post dose at Month 6 visit, and 1 hour post dose at Month 12 visit
Change From Baseline for Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Scores at Months 6 and 12
The KCCQ is a self-administered, 23-item questionnaire. KCCQ-OS scores are transformed to a 0 to 100 range, with lower scores denoting poorer quality of life.
Time frame: Day 1 (baseline), Months 6, and 12
Change From Baseline for EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Index Values at Months 6 and 12
The EQ-5D-5L is a brief, self-administered generic health status instrument. The instrument consists of 2 parts. In the first part, respondents are asked to rate their current health state on 5 dimensions (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having 5 levels of function (no problems, slight problems, moderate problems, severe problems, and extreme problems). The second part is a participant's self-rating of current health state on a Visual Analog Scale (EQ-5D VAS) with endpoints labeled 'best imaginable health state' (score of 100) and 'worst imaginable health state' (score of 0). The index values were calculated using the scoring algorithm based on preferences solicited from the Chinese population with 0 representing death and 1 representing full health. Higher EQ-5D-5L index value indicated a better quality of life. Change from baseline for EQ-5D-5L index values are reported for this outcome measure.
Time frame: Day 1 (baseline), Months 6, and 12
Change From Baseline for EuroQol VAS at Months 6 and 12
The EQ-5D-5L (5 levels version) is a brief, self-administered generic health status instrument. The instrument consists of 2 parts. In the first part, respondents are asked to rate their current health state on 5 dimensions (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having 3 levels of function (no problems, slight problems, moderate problems, severe problems and extreme problems). The second part is a participant's self-rating of current health state on a EQ-5D VAS with endpoints labeled 'best imaginable health state' (score of 100) and 'worst imaginable health state' (score of 0). The scores from the 5 dimensions may be used to calculate a single index value, also known as a utility score. EQ-5D VAS scores are reported for this outcome measure.
Time frame: Day 1 (baseline), Months 6, and 12
Change From Baseline for Physical Component Summary (PCS) for Short-Form Survey 12 (SF-12) at Months 6 and 12
SF-12 is developed as a shorter alternative to the SF-36 for use in large-scale studies. It is an instrument with different weights for scoring physical and mental health, and measures health-related quality of life with 12 items categorized in eight areas: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. This questionnaire was completed by the participant after the KCCQ and EQ-5D-5L, and prior to other required visit assessments. PCS score ranges from 0 to 100, and higher PCS score indicates a better quality of life. Change from baseline for PCS for SF-12 is reported for this outcome measure.
Time frame: Day 1 (baseline), Months 6, and 12
Change From Baseline for Mental Component Summary (MCS) for SF-12 at Months 6 and 12
SF-12 is developed as a shorter alternative to the SF-36 for use in large-scale studies. It is an instrument with different weights for scoring physical and mental health, and measures health-related quality of life with 12 items categorized in eight areas: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. This questionnaire was completed by the participant after the KCCQ and EQ-5D-5L, and prior to other required visit assessments. MCS score ranges from 0 to 100, and higher MCS score indicates a better quality of life. Change from baseline for MCS for SF-12 is reported for this outcome measure.
Time frame: Day 1 (baseline), Months 6, and 12
Plasma Concentrations of Tafamidis at Months 1, 6, and 12
Blood samples of approximately 3 mL, to provide an approximately 1 mL plasma, were collected for measurement of plasma concentrations of tafamidis at Months 1, 6, and 12 visits. Month 1 visit occurred 1 month post Day 1 +/- 1 week, Month 6 visit occurred 6 months post Day 1 +/- 2 weeks, and Month 12 visit occurred 12 months post Day 1 +/- 2 weeks or within 2 weeks after end of treatment.
Time frame: Predose and 3 hours post dose at Month 1 visit, 7 hours post dose at Month 6 visit, and 1 hour post at Month 12 visit
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.