Phase 3, open label study designed to obtain additional safety data for 20mg and 80mg tafamidis or tafamidis 61mg where available, continue providing to subjects who have completed 30 months of blinded treatment on Protocol B3461028 with tafamidis for up to 60 additional months, or until subject has access to tafamidis for ATTR-CM via prescription. Additional group of patients who have not previously participated in B3461028 included to received tafamidis until local availability by precription.
- Conditions
- Transthyretin amyloid cardiomyopathy (ATTR-CM)MedDRA version: 20.0 Level: LLT Classification code 10002020 Term: Amyloid cardiomyopathy System Organ Class: 100000004849Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2016-000868-42-GB
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 2000
1. Male and female subjects with TTR amyloid cardiomyopathy who have completed 30 months of study treatment on Protocol B3461028.
2. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
4. 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 hroughout 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 folliclestimulating hormone (FSH) level confirming the post-menopausal state.
All other female subjects (including females with tubal ligations) will be considered o be of childbearing potential.
Cohort B Inclusion Criteria
1.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.
2.Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
3.Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
4.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.
5.Documentation of the genetic testing for transthyretin amyloidosis (ie, original laboratory result, or copy)
6.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
1. 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.
2. Use of certain non-steroidal anti-inflammatory drugs (NSAIDs)
3. Liver and/or heart transplant, or implanted cardiac mechanical assist device.
4. Pregnant females (or planning to become pregnant during the study interval); breastfeeding females; male subjects with partners currently pregnant.
5. Require initiation of treatment with calcium channel blockers.
6. Urinary retention requiring chronic self-catheterization.
7. Breach of compliance with treatment/significant protocol violations during conduct of B3461028 for which the subject was accountable.
8. 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 he study.
9. Other severe acute or chronic medical or psychiatric condition or laboratory bnormality 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 an appropriate for entry into this study.
Cohort B Exclusion Criteria
Subjects in Cohort B with any of the following characteristics/conditions will not be included in the study:
1.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.
2.Use of certain non steroidal anti inflammatory drugs (NSAIDs)
3.Liver and/or heart transplant, or implanted cardiac mechanical assist device.
4.Require initiation of treatment with calcium channel blockers.
5.Urinary retention requiring chronic self catheterization.
6.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.
7.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.
8.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 in
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method