Safety And Efficacy Evaluation Of Fx-1006a In Patients With V122i Or Wild-Type Transthyretin (TTR) Amyloid Cardiomyopathy

NCT00935012 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: FX1B-303B3461026
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 7

Brief Summary

Open-label Safety and Efficacy Evaluation of Fx-1006a in Patients with V122i Or Wild-type Transthyretin (ttr) Amyloid Cardiomyopathy. Patients who successfully complete Fx1B-201 will report to the clinical unit on Day 0 to sign the informed consent form and determine eligibility for Protocol Fx1B-303. In addition, on Day 0, patients will have their entrance criteria reviewed, and medical histories and demographic characteristics obtained. The physical examination (including weight and vital signs) and the relevant end of study clinical laboratory tests (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, gamma glutamyl transferase, creatinine, total bilirubin, international normalized ratio, troponin I, troponin T, and amino-terminal B-type natriuretic peptide) from Protocol Fx1B-201 will be used for Protocol Fx1B-303. If more than 30 days has elapsed between the final study visit of Protocol Fx1B-201 and Day 0 of Protocol Fx1B-303, an abbreviated physical examination (including weight and vital signs) and clinical laboratory assessments must be performed on Day 0. Eligible patients will begin once-daily dosing with 20 mg Fx-1006A at home on Day 1 (i.e., first dose) and will return to the clinical unit for study visits every 6 months. Adverse events (AEs) and concomitant medication use will be collected at each 6-month visit to the clinical unit. Blood draws for clinical safety laboratory tests and abbreviated physical examinations (including weight and vital signs) will also be performed at each 6-month clinic visit. ECGs will be performed every 12 months on an annual basis. A telephone call will be made at 3-month intervals between clinic visits to assess safety and use of concomitant medications. For the evaluation of efficacy, the Patient Global Assessment, NYHA classification, KCCQ, 6-minute walk test, and efficacy-related clinical laboratory tests (serum levels of troponin T, troponin I, and NT-pro-BNP) will be determined every 6 months. In addition, echocardiograms will be performed every 12 months on an annual basis. An end of study visit including all safety and efficacy assessments will occur upon patient completion of the study, premature withdrawal (for any reason), or in the event of program discontinuation by the Sponsor.

Conditions

ATTR-CM; TTR-CM

Keywords

TTR, ATTR, cardiomyopathy, amyloidosis, tafamidis

Outcome Measures

Primary Outcomes (19)

• Percentage of Participants With Categories of Patient Global Assessment (PGA) for Follow-up Visit: Month 12

  Participants overall quality of life was measured by PGA. At follow-up visit, participants were asked, "How do you feel today as compared to when we talked with you at your last clinic visit for this study?" and participants responded to any of the following: markedly improved, moderately improved, mildly improved, unchanged, mildly worsened, moderately worsened or markedly worsened.

  Month 12

• Percentage of Participants With Categories of Patient Global Assessment (PGA) for Follow-up Visit: Month 60

  Participants overall quality of life was measured by PGA. At follow-up visit, participants were asked, "How do you feel today as compared to when we talked with you at your last clinic visit for this study?" and participants responded to any of the following: markedly improved, moderately improved, mildly improved, unchanged, mildly worsened, moderately worsened or markedly worsened.

  Month 60

• Number of Participants Classified on the Basis of New York Heart Association (NYHA) Classification at Baseline

  NYHA classified participants in 4 classes. Class I included participants with cardiac disease without limitations of physical activity. Ordinary physical activity did not cause undue fatigue, palpitation, dyspnea, or anginal pain. Class II included participants with cardiac disease with slight limitation of physical activity. They were comfortable at rest. Ordinary physical activity resulted in fatigue, palpitation, dyspnea, or anginal pain. Class III included participants with cardiac disease with marked limitation of physical activity. They were comfortable at rest. Less than ordinary physical activity caused fatigue, palpitation, dyspnea, or anginal pain. Class IV included participants with cardiac disease with the inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome might be present even at rest. If any physical activity was undertaken, discomfort was increased.

  Baseline

• Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Month 12

  NYHA classified participants in 4 classes: Class I: cardiac disease without limitations of physical activity. Ordinary physical activity caused no undue fatigue, palpitation, dyspnea or angina pain. Class II: cardiac disease with slight limitation of physical activity, comfortable at rest. Ordinary physical activity resulted in fatigue, palpitation, dyspnea or angina pain. Class III: cardiac disease with marked limitation of physical activity, comfortable at rest. Less than ordinary physical activity caused fatigue, palpitation, dyspnea or angina pain. Class IV: cardiac disease with inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or angina syndrome might be present even at rest. If any physical activity was undertaken, discomfort was increased. Participants with change from baseline were classified as improved (shifted from higher to lower class), unchanged (no change in class) or worsened (shifted from lower to higher class).

  Baseline, Month 12

• Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Month 60

  NYHA classified participants in 4 classes: Class I: cardiac disease without limitations of physical activity. Ordinary physical activity caused no undue fatigue, palpitation, dyspnea or angina pain. Class II: cardiac disease with slight limitation of physical activity, comfortable at rest. Ordinary physical activity resulted in fatigue, palpitation, dyspnea or angina pain. Class III: cardiac disease with marked limitation of physical activity, comfortable at rest. Less than ordinary physical activity caused fatigue, palpitation, dyspnea or angina pain. Class IV: cardiac disease with inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or angina syndrome might be present even at rest. If any physical activity was undertaken, discomfort was increased. Participants with change from baseline were classified as improved (shifted from higher to lower class), unchanged (no change in class) or worsened (shifted from lower to higher class).

  Baseline, Month 60

• Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 12

  6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance. Participants were asked to walk as far as possible for 6 minutes at a pace that was comfortable to them, and were permitted to slow down, to stop, and to rest as necessary. In this outcome measure, the total distance that a participant could walk in 6 minutes was evaluated.

  Baseline, Month 12

• Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 60

  6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance. Participants were asked to walk as far as possible for 6 minutes at a pace that was comfortable to them, and were permitted to slow down, to stop, and to rest as necessary. In this outcome measure, the total distance that a participant could walk in 6 minutes was evaluated.

  Baseline, Month 60

• Number of Participants Categorized Based on Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 12

  6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance. Participants were asked to walk as far as possible for 6 minutes at a pace that was comfortable to them, and were permitted to slow down, to stop, and to rest as necessary. In this outcome measure, participants were categorized based on the total distance walked as Level 1 = total distance walked less than (\<) 300 meter; Level 2 = total distance walked between 300 to 374.9 meter; Level 3 = total distance walked between 375 to 449.9 meter; Level 4 = total distance walked greater than or equal to (\>=) 450 meter.

  Month 12

• Number of Participants Categorized Based on Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 60

  6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance. Participants were asked to walk as far as possible for 6 minutes at a pace that was comfortable to them, and were permitted to slow down, to stop, and to rest as necessary. In this outcome measure, participants were categorized based on the total distance walked as Level 1 = total distance walked \< 300 meter; Level 2 = total distance walked between 300 to 374.9 meter; Level 3 = total distance walked between 375 to 449.9 meter; Level 4 = total distance walked \>=450 meter.

  Month 60

• Change From Baseline in Dyspnea and Fatigue Scores During 6 Minute Walk Test (6MWT) at Month 12

  6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance. Participants were asked to walk as far as possible for 6 minutes at a pace that was comfortable to them, and were permitted to slow down, to stop, and to rest as necessary. Dyspnea: participants were asked to rate the difficulty of their breathing, pre-walk and post-walk at each visit, on a scale of range 0 (no breathlessness at all) to 10 (maximum breathlessness). Higher scores indicated more severity. Fatigue: participants were asked to rate the how tired they felt, pre-walk and post-walk at each visit, on a scale of range 0 (not at all) to 10 (maximal) Higher scores indicated more fatigue. At each visit, scores for pre-walk test, post-walk test and within visit difference (difference from post-walk to pre-walk) were evaluated. Change from baseline was calculated for each pre-walk test, post-walk test and within visit difference at Month 12.

  Baseline, Month 12

• Change From Baseline in Dyspnea and Fatigue Scores During 6 Minute Walk Test (6MWT) at Month 60

  6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance. Participants were asked to walk as far as possible for 6 minutes at a pace that was comfortable to them, and were permitted to slow down, to stop, and to rest as necessary. Dyspnea: participants were asked to rate the difficulty of their breathing, pre-walk and post-walk at each visit, on a scale of range 0 (no breathlessness at all) to 10 (maximum breathlessness). Higher scores indicated more severity. Fatigue: participants were asked to rate the how tired they felt, pre-walk and post-walk at each visit, on a scale of range 0 (not at all) to 10 (maximal) Higher scores indicated more fatigue. At each visit, scores for pre-walk test, post-walk test and within visit difference (difference from post-walk to pre-walk) were evaluated. Change from baseline was calculated for each pre-walk test, post-walk test and within visit difference at Month 60.

  Baseline, Month 60

• Number of Participants Categorized on Basis of Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 12

  6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance. Participants were asked to walk as far as possible for 6 minutes at a pace that was comfortable to them, and were permitted to slow down, to stop, and to rest as necessary. In this outcome measure, participants on basis of change from baseline in total distance walked were categorized as worsened, unchanged or improved. If distance walked at a visit was greater than distance walked at baseline, then categorized as 'improved'. If distance walked at a visit was equal to distance walked at baseline, then categorized as 'unchanged'. If distance walked at a visit was less than distance walked at baseline, then categorized as 'worsened'.

  Baseline, Month 12

• Number of Participants Categorized on Basis of Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 60

  6MWT is a sub-maximal exercise test used to assess aerobic capacity and endurance. Participants were asked to walk as far as possible for 6 minutes at a pace that was comfortable to them, and were permitted to slow down, to stop, and to rest as necessary. In this outcome measure, participants on basis of change from baseline in total distance walked were categorized as worsened, unchanged or improved. If distance walked at a visit was greater than distance walked at baseline, then categorized as 'improved'. If distance walked at a visit was equal to distance walked at baseline, then categorized as 'unchanged'. If distance walked at a visit was less than distance walked at baseline, then categorized as 'worsened'.

  Baseline, Month 60

• Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Summary Score at Month 12

  KCCQ is a 23-item participant-completed questionnaire that assesses health status and health-related quality of life in participants with heart failure. Eight domain scores were calculated for the KCCQ: physical limitation, social limitation, quality of life, self-efficacy, symptom stability, symptom frequency, symptom burden, and total symptoms (calculated as the mean of symptom frequency and symptom burden scores). Two summary scores were calculated: clinical summary (calculated as mean of physical limitation and total symptom scores) and overall summary (calculated as mean of physical limitation, social limitation, total symptoms, and quality of life scores). Each domain and both summary scores were scaled to range from 0 (worse health status) to 100 (best health status); higher scores represented better health status.

  Baseline, Month 12

• Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Summary Score at Month 60

  KCCQ is a 23-item participant-completed questionnaire that assesses health status and health-related quality of life in participants with heart failure. Eight domain scores were calculated for the KCCQ: physical limitation, social limitation, quality of life, self-efficacy, symptom stability, symptom frequency, symptom burden, and total symptoms (calculated as the mean of symptom frequency and symptom burden scores). Two summary scores were calculated: clinical summary (calculated as mean of physical limitation and total symptom scores) and overall summary (calculated as mean of physical limitation, social limitation, total symptoms, and quality of life scores). Each domain and both summary scores were scaled to range from 0 (worse health status) to 100 (best health status); higher scores represented better health status.

  Baseline, Month 60

• Change From Baseline in Troponin I and Troponin T Serum Levels at Month 12

  Troponin I and troponin T are the cardiac markers. Troponin I and troponin T are part of the troponin complex, where troponin I is bound to actin in thin myofilaments and troponin T is bound to tropomyosin. Higher level of these markers is indicative of heart damage.

  Baseline, Month 12

• Change From Baseline in Troponin I and Troponin T Serum Levels at Month 60

  Troponin I and troponin T are the cardiac markers. Troponin I and troponin T are part of the troponin complex, where troponin I is bound to actin in thin myofilaments and troponin T is bound to tropomyosin. Higher level of these markers is indicative of heart damage.

  Baseline, Month 60

• Change From Baseline in Amino-Terminal B-type Natriuretic Peptide (NT-proBNP) Serum Level at Month 12

  NT-proBNP is biomarker of cardiac stress (myocardial necrosis and increased filling pressures/ left ventricular \[LV\] wall stress).

  Baseline, Month 12

• Change From Baseline in Serum Levels of Amino-Terminal B-type Natriuretic Peptide (NT-proBNP) at Month 60

  NT-proBNP is biomarker of cardiac stress (myocardial necrosis and increased filling pressures/ LV wall stress).

  Baseline, Month 60

Secondary Outcomes (18)

• Percentage of Participants With Categories of Patient Global Assessment (PGA) for Follow-up Visit: Months 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126 and 132

  Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132

• Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Months 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126 and 132

  Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132

• Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Months 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120 and 132

  Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 132

• Number of Participants Categorized Based on Total Distance Walked During 6 Minute Walk Test (6MWT) at Baseline, Months 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126 and 132

  Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132

• Change From Baseline in Dyspnea and Fatigue Scores During 6 Minute Walk Test (6MWT) at Months 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120 and 132

  Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 132

Study Arms (1)

Open-Label

EXPERIMENTAL

Drug: tafamidis

Interventions

tafamidis DRUG

Once daily 20 mg oral tafamidis (soft gelatin capsule)

Open-Label

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient successfully completed Protocol Fx1B-201.
• If female; patient is post menopausal. If male, female partner is post-menopausal. If female is of child bearing potential, willing to use acceptable method of birth control up to 3 months after last dose (included female partners of male participants).
• Patient is willing to comply with protocol.

You may not qualify if:

• Patient did not successfully complete Fx1B-201.
• Chronic use of NSAIDS.
• Patient has a clinically significant medication condition that increases risk of study participation.
• Patient has received heart or liver transplant.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (7)

Emory University School of Medicine

Atlanta, Georgia, 30322-4510, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Clinical Cardiovascular Research Laboratory for the Elderly (CCRLE)

New York, New York, 10034-1159, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Cardiomyopathies; Amyloidosis

Interventions

tafamidis

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2009
• First Posted: July 8, 2009
• Study Start: September 30, 2009
• Primary Completion: November 20, 2019
• Study Completion: November 20, 2019
• Last Updated: January 5, 2021
• Results First Posted: January 5, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share

Locations

US (7)