Clinical trial NCT04828993: The Effect Of Tafamidis Meglumine In Transthyretin Amyloid Polyneuropathy Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Transthyretin Amyloid Polyneuropathy (ATTR-PN)
Keywords: tafamidis meglumine
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-04-02
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. Male or female participants between the ages of 18 and 80 years.
2. Participants have amyloid documented by biopsy
3. Participants must have a TTR mutation that is associated with ATTR-PN.
4. Participants have peripheral and/or autonomic neuropathy
5. Stages of disease according to symptom severity-stage I.

Exclusion Criteria:

1. 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.
2. Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs.
3. 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:
4. 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).
5. Participant has primary (light chain) or secondary amyloidosis.
6. If female, participant is pregnant or breast feeding, or plans to be pregnant or breast feeding in the next 18 months.
7. Participant has received prior liver or any other organ except cornea transplantation.
8. Participant requires significant assistance with ambulation or is wheel chair bound.
9. Participants with cardiomyopathy specific TTR mutations.
10. Participant has other causes of sensorimotor neuropathy.

Primary outcomes:
measure: Change From Baseline in Neuropathy Impairment Score-lower Limb (NIS-LL) Total Score at Week 72
timeFrame: Baseline, Week 72
Secondary outcomes:
measure: Change From Baseline in Neuropathy Impairment Score-lower Limb (NIS-LL) Total Score at Weeks 24, and 48
timeFrame: Baseline, Week 24, Week 48
measure: 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
timeFrame: Baseline, Week 24, Week 48, Week 72
measure: Change From Baseline in 5 Domains of Norfolk QOL-DN at Weeks 24, 48, and 72
timeFrame: Baseline, Week 24, Week 48, Week 72
measure: Change From Baseline in Modified Body Mass Index (mBMI) at Weeks 4, 8, 12, 24, 36, 48, and 72
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, and 72
measure: 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
timeFrame: Baseline, Weeks 24, 48, and 72
measure: Change From Baseline in EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) Index Score at Weeks 24, 48, and 72
timeFrame: Baseline, Weeks 24, 48, and 72
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Week 77
measure: Number of Participants With Categorical Vital Signs Data
timeFrame: Baseline up to Week 72
measure: Number of Participants With Categorical Electrocardiogram (ECG) Data
timeFrame: Baseline up to Week 72
measure: Number of Participants With Clinically Significant Echocardiography (ECHO) Value Related to Primary Diagnosis (Transthyretin Amyloidosis [ATTR]) at Baseline, Weeks 24, 48, and 72
timeFrame: Baseline, Weeks 24, 48, and 72
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Baseline up to Week 72
measure: Transthyretin (TTR) Concentrations on Day 1 (Baseline), and at Weeks 8, 12, 24, 48, and 72
timeFrame: Baseline, Weeks 8, 12, 24, 48, and 72
measure: TTR Stabilization and Percentage and 95% CI of Responders in TTR Stabilization at Post Baseline Visit
timeFrame: Weeks 8, 12, 24, 48, and 72
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: NanFang Hospital of Southern Medical University
state: Guangdong
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
state: Shanghai
city: Beijing
country: China
facility: Peking union hospital of Chinese academy of medical sciences
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
city: Beijing
country: China
facility: Tiantan Hospital Capital Medical University
city: Beijing
country: China
facility: Peking union hospital of Chinese academy of medical sciences
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: