Clinical trial NCT00935012: Safety And Efficacy Evaluation Of Fx-1006a In Patients With V122i Or Wild-Type Transthyretin (TTR) Amyloid Cardiomyopathy
Official title: Open-Label Safety And Efficacy Evaluation Of Fx-1006a In Patients With V122i Or Wild-Type Transthyretin (TTR) Amyloid Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ATTR-CM
TTR-CM
Keywords: TTR, ATTR, cardiomyopathy, amyloidosis, tafamidis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-07-08
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of Participants With Categories of Patient Global Assessment (PGA) for Follow-up Visit: Month 12
timeFrame: Month 12
measure: Percentage of Participants With Categories of Patient Global Assessment (PGA) for Follow-up Visit: Month 60
timeFrame: Month 60
measure: Number of Participants Classified on the Basis of New York Heart Association (NYHA) Classification at Baseline
timeFrame: Baseline
measure: Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Month 12
timeFrame: Baseline, Month 12
measure: Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Month 60
timeFrame: Baseline, Month 60
measure: Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 60
timeFrame: Baseline, Month 60
measure: Number of Participants Categorized Based on Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 12
timeFrame: Month 12
measure: Number of Participants Categorized Based on Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 60
timeFrame: Month 60
measure: Change From Baseline in Dyspnea and Fatigue Scores During 6 Minute Walk Test (6MWT) at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Dyspnea and Fatigue Scores During 6 Minute Walk Test (6MWT) at Month 60
timeFrame: Baseline, Month 60
measure: Number of Participants Categorized on Basis of Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 12
timeFrame: Baseline, Month 12
measure: Number of Participants Categorized on Basis of Change From Baseline in Total Distance Walked During 6 Minute Walk Test (6MWT) at Month 60
timeFrame: Baseline, Month 60
measure: Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Summary Score at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Summary Score at Month 60
timeFrame: Baseline, Month 60
measure: Change From Baseline in Troponin I and Troponin T Serum Levels at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Troponin I and Troponin T Serum Levels at Month 60
timeFrame: Baseline, Month 60
measure: Change From Baseline in Amino-Terminal B-type Natriuretic Peptide (NT-proBNP) Serum Level at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Serum Levels of Amino-Terminal B-type Natriuretic Peptide (NT-proBNP) at Month 60
timeFrame: Baseline, Month 60
Secondary outcomes:
measure: 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
timeFrame: Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132
measure: 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
timeFrame: Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132
measure: 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
timeFrame: Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 132
measure: 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
timeFrame: Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132
measure: 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
timeFrame: Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 132
measure: Number of Participants Categorized on Basis of 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
timeFrame: Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 132
measure: Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Summary Score at Months 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126 and 132
timeFrame: Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132
measure: Number of Participants With Abnormalities in Echocardiography
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
measure: Change From Baseline in Troponin I and Troponin T Serum Levels at Months 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120 and 126
timeFrame: Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120 and 126
measure: Change From Baseline in Amino-Terminal B-type Natriuretic Peptide (NT-proBNP) Serum Level at Months 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120 and 126
timeFrame: Baseline, Month 6, 18, 24, 30, 36, 42, 48, 54, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126
measure: Number of Participants With All-cause Hospitalization and Cardiac-related Hospitalization Events
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
measure: Time to All-cause Mortality and Cardiac-Related Mortality
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
measure: Number of Participants With Treatment-Related Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
measure: Number of Participants With Clinically Significant Physical Examination Findings
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
measure: Number of Participants With Any Concomitant Medications
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Post-Month 12 up to Month 132 (approximately 10 years) of Study FX1B-303
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: New York
country: United States
facility: Clinical Cardiovascular Research Laboratory for the Elderly (CCRLE)
state: New York
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: