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The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy

Last updated on November 9, 2019

FOR MORE INFORMATION
Study Location
Emory University School of Medicine
Atlanta, Georgia, 30322 United States
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Cardiomyopathy
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
40 + years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. Patient is > 40 years-old.

2. Patient participated in FoldRx Study Fx-001 (TRACS) OR Patient has documented TTR
amyloid cardiomyopathy and NYHA Classification of I or II.

TTR amyloid cardiomyopathy is defined as:

1. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype and presence of
amyloid in cardiac biopsy tissue (as determined by congo red stain, alcin blue
stain, or immunohistochemical TTR analysis), or

2. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype, evidence of
cardiac involvement by echocardiography with left ventricle wall thickness > 12
mm and presence of amyloid in non-cardiac biopsy tissue (as determined by congo
red stain, alcin blue stain, or immunohistochemical TTR analysis), or

3. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype and
presence of TTR amyloid deposits in cardiac biopsy tissue (as determined by
congo red stain and immunohistochemical TTR analysis), or

4. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype,
evidence of cardiac involvement by echocardiography with left ventricle wall
thickness > 12 mm and presence of TTR amyloid deposits in non-cardiac biopsy
tissue (as determined by congo red stain and immunohistochemical TTR analysis).

3. Patient's symptoms of congestive heart failure (CHF) have been optimally managed
prior to baseline, as assessed by the Principal Investigator. Optimal CHF management
includes stable drug regimen for ≥ 4 weeks prior to enrollment and stable dose of
beta blocker for ≥ 3 months prior to enrollment.

4. If female, patient is post-menopausal. If male with a female partner of childbearing
potential, willing to use an acceptable method of birth control for the duration of
the study and for at least 3 months after the last dose of study medication.

5. Patient is, in the opinion of the Investigator, willing and able to comply with the
study medication regimen and all other study requirements

Exclusion criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

1. Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs),
defined as greater than 3-4 times/month. The following NSAID are allowed:
acetylsalicylic acid, etodolac, ibuprofen, indomethicin, ketoprofen, nabumetone,
naproxen, nimesulide, piroxicam, and sulindac.

2. Patient has a TTR mutation other than V122I.

3. Patient has primary or secondary amyloidosis.

4. Patient has received prior liver or heart transplantation.

5. Patient with positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis
C virus (anti-HCV), and/or human immunodeficiency virus (HIV).

6. Patient has renal failure requiring dialysis.

7. Patient has moderate or severe hepatic impairment (assessed by Child-Pugh).

8. Patient has liver function test abnormalities: alanine transaminases (ALT) and/or
aspartate transaminases (AST) > 2 times upper limit of normal (ULN) that, in the
medical judgment of the Investigator, are due to reduced liver function or active
liver disease.

9. Patient has prior non-amyloid cardiac disease, such as myocardial infarction due to
obstructive coronary artery disease, active non-amyloid cardiomyopathy (i.e.,
symptomatic left ventricular dysfunction from any cause other than amyloid), or
symptomatic valvular heart disease that significantly contribute to the patient's
underlying cardiac signs or symptoms.

10. Patient has a co-morbidity anticipated to limit survival to less than 12 months.

11. Patient received an investigational drug/device in another clinical investigational
study within 60 days before Baseline (Day 0).

12. Patient had active alcohol or substance abuse within 60 days before Baseline (Day 0).

13. Patient has a history of documented noncompliance.

NCT00694161
Pfizer
Completed
The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy

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Descriptive Information
Brief Title  ICMJE The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy
Official Title  ICMJE The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy
Brief Summary

Open-label, multicenter, international, single-treatment study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with V122I or wild-type TTR amyloid cardiomyopathy.

The study will be conducted in two parts. Part 1 will include a six-week dosing period during which all enrolled patients will self-administer oral Fx-1006A 20 mg soft gelatin capsules once daily for six weeks. At Week 6, blood samples will be collected from each patient to determine TTR stabilization. Patients who complete the Week 6 visit will continue taking daily oral Fx 1006A 20 mg for up to a total of 12 months during Part 2 of this study. If it is determined that a patient is not stabilized at Week 6 (based on TTR stabilization data), the patient will be discontinued from the study. Safety and clinical outcomes will be evaluated during Part 2 of this study.

Two whole blood samples for pharmacodynamic assessments (TTR stabilization) and pharmacokinetic assessments (Fx-1006A concentrations as well as calculated steady-state parameters) will be collected at Baseline and Week 6. At Months 6 and 12, two whole blood samples will be collected for pharmacodynamic assessments, and four whole blood samples (two samples per time point) will be collected for pharmacokinetic assessments to be utilized in population pharmacokinetic modeling.

Echocardiography, chest x-ray, cardiac MRI, and 24-hour Holter monitoring will be conducted at Baseline, and Months 6 and 12. Six-minute walk test and quality of life utilizing the Patient Global Assessment, KCCQ, and SF-36 will be assessed at Baseline, and Months 3, 6, and 12. NYHA Classification will be assessed at Baseline, Week 6, and Months 3, 6, and 12. Serum markers of troponin I and T, and NT-pro-BNP levels will be assessed at each study visit.

Safety and tolerability will be assessed throughout the study. Vital signs, 12-lead ECG, blood and urine samples for clinical laboratory tests (serum chemistry, hematology, coagulation panel, and urinalysis), AEs, and concomitant medications (including diuretic usage) will be assessed at each study visit. Abbreviated physical examinations will be conducted at Baseline, Weeks 2 and 6, and Months 3 and 6, and a complete physical examination will be conducted at Month 12.

Clinic visits will be conducted during Screening (Days -30 to -1) and Baseline (Day 0); procedures scheduled for the Baseline visit may be conducted over a period of one week to accommodate patient scheduling. All Baseline procedures must be completed prior to the first self-administered dose on Day 1. Day 1 will be defined as administration of the first dose of study medication, which patients will self-administer at home. During treatment, clinic visits will be conducted at Week 2 (± 2 days), Week 6 (± 1 week), Month 3 (± 1 week), Month 6 (± 2 weeks), and Month 12 (± 2 weeks). Procedures scheduled for the Month 6 and 12 visits may occur over one week during the visit window to accommodate patient scheduling. Monthly telephone contacts (± 1 week of the scheduled date) will be made during months in which no clinical site visits are scheduled (Months 4, 5, 7, 8, 9, 10, and 11) for assessment of AEs and concomitant medications. A final telephone contact to assess AEs and concomitant medication usage will be made 30 days after the last dose of study medication for each patient.

Patients who discontinue from the study at any time will have a final visit performed, including all safety assessments, at the time of discontinuation. Any patient discontinuing after the Month 6 visit will also have all exploratory assessments performed.

Detailed DescriptionNot Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cardiomyopathy
Intervention  ICMJE Drug: Fx-1006A
Fx-1006A 20mg soft gelatin capsules once daily (at the same time each day) for 12 months
Study Arms  ICMJE Experimental: Fx-1006A
Intervention: Drug: Fx-1006A
Publications *


*   Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 3, 2011)
35
Original Estimated Enrollment  ICMJE
 (submitted: June 9, 2008)
20
Actual Study Completion Date  ICMJE January 2010
Actual Primary Completion DateJanuary 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient is > 40 years-old.
  2. Patient participated in FoldRx Study Fx-001 (TRACS) OR Patient has documented TTR amyloid cardiomyopathy and NYHA Classification of I or II.

    TTR amyloid cardiomyopathy is defined as:

    1. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype and presence of amyloid in cardiac biopsy tissue (as determined by congo red stain, alcin blue stain, or immunohistochemical TTR analysis), or
    2. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype, evidence of cardiac involvement by echocardiography with left ventricle wall thickness > 12 mm and presence of amyloid in non-cardiac biopsy tissue (as determined by congo red stain, alcin blue stain, or immunohistochemical TTR analysis), or
    3. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype and presence of TTR amyloid deposits in cardiac biopsy tissue (as determined by congo red stain and immunohistochemical TTR analysis), or
    4. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype, evidence of cardiac involvement by echocardiography with left ventricle wall thickness > 12 mm and presence of TTR amyloid deposits in non-cardiac biopsy tissue (as determined by congo red stain and immunohistochemical TTR analysis).
  3. Patient's symptoms of congestive heart failure (CHF) have been optimally managed prior to baseline, as assessed by the Principal Investigator. Optimal CHF management includes stable drug regimen for ? 4 weeks prior to enrollment and stable dose of beta blocker for ? 3 months prior to enrollment.
  4. If female, patient is post-menopausal. If male with a female partner of childbearing potential, willing to use an acceptable method of birth control for the duration of the study and for at least 3 months after the last dose of study medication.
  5. Patient is, in the opinion of the Investigator, willing and able to comply with the study medication regimen and all other study requirements

Exclusion Criteria:

  1. Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month. The following NSAID are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethicin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac.
  2. Patient has a TTR mutation other than V122I.
  3. Patient has primary or secondary amyloidosis.
  4. Patient has received prior liver or heart transplantation.
  5. Patient with positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), and/or human immunodeficiency virus (HIV).
  6. Patient has renal failure requiring dialysis.
  7. Patient has moderate or severe hepatic impairment (assessed by Child-Pugh).
  8. Patient has liver function test abnormalities: alanine transaminases (ALT) and/or aspartate transaminases (AST) > 2 times upper limit of normal (ULN) that, in the medical judgment of the Investigator, are due to reduced liver function or active liver disease.
  9. Patient has prior non-amyloid cardiac disease, such as myocardial infarction due to obstructive coronary artery disease, active non-amyloid cardiomyopathy (i.e., symptomatic left ventricular dysfunction from any cause other than amyloid), or symptomatic valvular heart disease that significantly contribute to the patient's underlying cardiac signs or symptoms.
  10. Patient has a co-morbidity anticipated to limit survival to less than 12 months.
  11. Patient received an investigational drug/device in another clinical investigational study within 60 days before Baseline (Day 0).
  12. Patient had active alcohol or substance abuse within 60 days before Baseline (Day 0).
  13. Patient has a history of documented noncompliance.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00694161
Other Study ID Numbers  ICMJE FX1B-201
B3461025
Has Data Monitoring CommitteeNo
U.S. FDA-regulated ProductNot Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible PartyPfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Jeff Packman, MBAFoldRx Pharmaceuticals, Inc
PRS AccountPfizer
Verification DateJanuary 2013

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

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