Principal Investigator: Jose Nativi-Nicolau
Keywords: Heart Failure , Amyloidosis Department: Cardiovascular Medicine
IRB Number: 00095963 Co Investigator: Jose Nativi-Nicolau
Specialty: Cardiology, Cardiology, Cardiology
Sub Specialties: General Cardiology, Heart Failure
Recruitment Status: Recruiting

Contact Information

Ashlee Rooks
ashlee.rooks@hsc.utah.edu
801-585-7295

Brief Summary

Cohort A B3461045 Pfizer IRB #95963:  Is a follow-up study to the B3461028 Pfizer ATTR-ACT study IRB #78462 (which is now completed/ closed).  The Cohort A study is currently closed to enrollment and is actively seeing patients for their scheduled follow-up visits.  Patients are scheduled for a clinic visit every 6 months, followed by a 3 month phone visit. There are 3 active subjects in the Cohort A portion of the study.  The main objectives of Cohort A is to obtain additional, long-term, safety data for tafamidis in subjects with transthyretin amyloid cardiomyopathy (TTR-CM). And to provide investigational product, tafamidis, to TTR-CM subjects who complete 30 months of blinded treatment on protocol B3461028.

Cohort B: Amendment to ATTR-ACT Ext. Study IRB #95963.  This Amendment is to allow our site to screen/ enroll 10-20 patients with TTR Amyloidosis and give them treatment free of charge (expanded access) until the study drug is approved by the FDA.  Since there are currently no FDA approved medications for patients with this rare disease, and the recent data results obtained from the ATTR-ACT study (IRB #78462) showcased an impressive 33% decrease in patient mortality for those who took the drug, the PI Jose Nativi-Nicolau is eager to enroll as many subjects under the newly proposed Cohort B Amendment.

The main objectives of Cohort B is to obtain additional, long-term, safety data for tafamidis in subjects with transthyretin amyloid cardiomyopathy (ATTR-CM). And to provide investigational product, tafamidis, to enrolled subjects until local availability by prescription for the ATTR-CM indication.

 

Inclusion Criteria

Cohort A Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

Male and female subjects with TTR amyloid cardiomyopathy who have completed 30 months of study treatment on Protocol B3461028 (ATTR-ACT IRB #78462.)

Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use 2 highly effective methods of contraception throughout the study and for at least 28 days after the last dose of assigned treatment.

Female subjects who are not of childbearing potential (ie, meet at least 1 of the following criteria):

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or

Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle- stimulating hormone (FSH) level confirming the post-menopausal state.

All other female subjects (including females with tubal ligations) will be considered to be of childbearing potential.

 

Cohort B Inclusion Criteria

Subjects in Cohort B must meet all of the following Inclusion Criteria to be eligible for enrollment into the study:

Male or female subject of at least 18 years of age (or the minimum country specific age of consent if >18) and participates at a study site in an eligible country listed in Protocol Appendix 5.

Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:

  • Is not a Woman of Childbearing Potential (WOCBP) (see definition Section 4.3.1)

OR

  • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year) (see Section 4.3) during the intervention period and for at least 28 days after the last dose of study intervention, which corresponds to the time needed to eliminate any study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.  
    The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

Documentation of the genetic testing for transthyretin amyloidosis (ie, original laboratory result, or copy)

Documentation of diagnosis and criteria used (e.g. congestive heart failure and scintigraphy with tracer eg 99mTC DPD [99mTC 3,3 diphosphono 1,2 propano dicarboxylic acid], 99mTC PYP [Pyrophosphate] and also 99mTC HMDP [hydroxymethylene diphosphonate] or Congestive heart failure and presence of amyloid deposits in biopsy tissue, e.g. fat aspirate, salivary gland, median nerve connective tissue sheath, or cardiac [amyloid demonstrated per appropriate stain such as Congo red or alcian blue stain])

Documentation that primary (light chain) amyloidosis disease has been evaluated and ruled out (ie, original laboratory result, or copy)

Evidence of NYHA classification I, II, III, or IV

Exclusion Criteria

Cohort A Exclusion Criteria

Subjects with any of the following characteristics/conditions will not be included in the study:

Chronic use of diflunisal, TTR stabilizer, tauroursodeoxycholate, doxycycline, digitalis, patisiran, calcium channel blockers, investigational drug(s) or other experimental interventions, other than tafamidis, independently or as part of a study within 30 months prior to enrollment, or inotersen within 6 months prior to enrollment.

Use of certain non-steroidal anti-inflammatory drugs (NSAIDs)*

Liver and/or heart transplant, or implanted cardiac mechanical assist device.

Pregnant females (or planning to become pregnant during the study interval); breastfeeding females; male subjects with partners currently pregnant.

Require initiation of treatment with calcium channel blockers.

Urinary retention requiring chronic self-catheterization.

Breach of compliance with treatment/significant protocol violations during conduct of B3461028 for which the subject was accountable.

Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.

Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

*Use of NSAIDs other than those noted below was prohibited during participation in parent study B3461028 and is prohibited during Study B3461045.  Some NSAIDs, like diflunisal, can bind to the thyroxine binding sites on transthyretin (Almeida 2004).1   Permitted NSAIDs include: acetylsalicylic acid, etodolac, ibuprofen, indomethacin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac. Use of any other NSAIDs requires agreement with the Sponsor’s clinician or medical monitor.

Use of any investigational therapy during the study is not permitted.

Use of diflunisal or any other investigational therapy during the study is prohibited.

Additionally, the use of tauroursodeoxycholate and doxycycline is not permitted.

Digitalis and calcium channel blockers (eg, verapamil, diltiazem) are prohibited concomitant medications because they bind to amyloid fibrils and may lead to increased toxicity

COHORT B EXCLUSION CRITERIA

Subjects in Cohort B with any of the following characteristics/conditions will not be included in the study:

Chronic use of diflunisal, TTR stabilizer, tauroursodeoxycholate, doxycycline, digitalis, patisiran, calcium channel blockers, investigational drug(s) or other experimental interventions, other than tafamidis, independently or as part of a study within 30 days prior to enrollment, or inotersen within 6 months prior to enrollment.

Use of certain non-steroidal anti-inflammatory drugs (NSAIDs) [Section 5.8.1].

Liver and/or heart transplant, or implanted cardiac mechanical assist device.

Require initiation of treatment with calcium channel blockers.

Urinary retention requiring chronic self-catheterization.

Subjects with heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg prior myocardial infarction with documented history of cardiac enzymes and ECG changes), or uncorrected valvular disease and not primarily due to transthyretin amyloid cardiomyopathy.

Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.

Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.