|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Transthyretin Amyloidosis (ATTR)
|Medical condition in easily understood language
|A condition characterised by the buildup of abnormal deposits of a protein called amyloid in the body's organs and tissues including nerve tissue resulting in a loss of sensation in the extremities
|Body processes [G] - Metabolic Phenomena [G03]
|E.1.2 Medical condition or disease under investigation
|Familial amyloid polyneuropathy
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|- To obtain additional, long-term, open-label safety and efficacy data for tafamidis in
subjects with transthyretin (TTR) familial amyloid polyneuropathy (TTR-FAP).
-To continue to provide the investigational product Tafamidis to subjects with TTR-FAP
who have completed Protocol Fx-006 or Protocol Fx1A-201.
|Secondary objectives of the trial
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|Any subject determined during this study to have developed severe chronic renal impairment (creatinine clearance <30 mL/minute) will be asked to consent to participate in a renal sub-study. The primary purpose of this sub-study is to obtain data on the pharmacokinetics (PK) of tafamidis in subjects with severe renal dysfunction.
|Principal inclusion criteria
|Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
-Subject has successfully completed either Protocol Fx-006 or Fx-1A-201.
-If female, subject is post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control (ie, hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) throughout the study and for 3 months from the end of the study. (A condom alone is not considered an acceptable method of birth control).
-Male or female subjects with TTR-FAP who have not undergone liver or heart transplantation at time of enrollment and who have successfully completed Protocol Fx-006 or Protocol Fx1A-201.
|Principal exclusion criteria
|1. Subject has not successfully completed either Protocol Fx-006 or Fx1A-201.
2. Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3 to 4 times/month. The following NSAIDs are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethacin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac.
3. If female, subject is pregnant or breast feeding.
4. Clinically significant medical condition that, in the opinion of the investigator, would place the subject at an increased risk to participate in the study.
5. An ALT and AST value >3X ULN that in the medical judgment of the investigator is due to reduced liver function or active liver disease.
6. The subject has received a liver or heart transplant.
7. Sexually active males with partners of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 3 months after last dose of investigational product.
|E.5 End points
|Primary end point(s)
|The efficacy endpoints for this study are:
-The Neuropathy Impairment Score (NIS);
-The Total Quality of Life (TQOL) score as measured using the Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) questionnaire;
-The Karnofsky Performance Scale Index;
-Assessment of subject ambulation.
The safety endpoints for this study are:
The incidence of treatment-emergent adverse events (TEAEs), physical examinations, clinical laboratory testing, use of concomitant medications, ECGs, echocardiography parameters, and vital signs.
|Timepoint(s) of evaluation of this end point
|Details are provided in the protocol section 6.2
|Secondary end point(s)
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|This is an open label trial which will continue for up to 10 years or until subject has access to tafamidis for TTR FAP via prescription. Upon regulatory approval for the treatment of TTR-FAP in their respective country, and access to prescription tafamidis, subjects may be withdrawn from the study. The decision to withdraw subjects in a country will be done in consultation between the investigator and the sponsor.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days