Safety And Efficacy Evaluation Of Fx-1006A In Subjects With Transthyretin Amyloidosis

• ClinicalTrials.gov Identifier: NCT00925002
• Recruitment Status: Active, not recruiting
• First Posted: June 19, 2009
• Last Update Posted: April 28, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

This is a Phase 3, open-label study designed to obtain additional long-term safety and efficacy data for oral tafamidis (20 mg soft gelatin capsule) administered once daily (QD). In addition, this study continued to provide tafamidis to Val30Met subjects who had completed Protocol Fx-006 (a 1-year, open-label extension study to Protocol Fx-005 which was a randomized, double-blind, placebo-controlled, 18-month study to evaluate the safety and efficacy of tafamidis) or non-Val30Met subjects who had completed Protocol Fx1A-201 (a Phase 2, open-label study to evaluate TTR stabilization, safety, and tolerability of tafamidis) for up to 10 years or until subjects had access to tafamidis for ATTR-PN via prescription. Upon regulatory approval for the treatment of ATTR-PN in their respective country and access to prescription tafamidis, subjects may have been withdrawn from the study. Such subjects were considered study completers.

Condition or disease	Intervention/treatment	Phase
ATTR-PN	Drug: Tafamidis	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 93 participants
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: OPEN-LABEL SAFETY AND EFFICACY EVALUATION OF FX-1006A IN SUBJECTS WITH TRANSTHYRETIN (TTR) AMYLOIDOSIS
• Actual Study Start Date: August 5, 2009
• Estimated Primary Completion Date: May 30, 2020
• Estimated Study Completion Date: May 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Open-Label	Drug: Tafamidis; 20 mg oral Fx-1006A daily

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with a change from baseline in Neuropathy Impairment Score (NIS) [ Time Frame: Baseline up to 10 years ]
2. Percentage of patients with a change from baseline in Total Quality of Life (TQOL) score [ Time Frame: Baseline up to 10 years ]
3. Number or Percentage of patients with a change from baseline in Karnofsky Performance Scale Index [ Time Frame: Baseline up to 10 years ]
4. Percentage of patients with a change in subject ambulation as measured by modified Polyneuropathy Disability (mPND) score [ Time Frame: Baseline up to 10 years ]

Secondary Outcome Measures :

1. Incidence of treatment emergent adverse events from baseline through 10 years [ Time Frame: Baseline up to 10 years ]
2. Number or percentage of patients with change from baseline in Clinical Laboratory parameters [ Time Frame: Baseline up to 10 years ]
3. Number of patients with change in ECG parameters [ Time Frame: Baseline up to 10 years ]
4. Number or percentage of patients with change from baseline in Vital sign measurements [ Time Frame: Baseline up to 10 years ]
5. Descriptive summary of physical examination findings for patients through 10 years [ Time Frame: Baseline up to 10 years ]
6. Descriptive summary of concomitant medication use for patients through 10 years [ Time Frame: Baseline up to 10 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion criteria:

• Subject had successfully completed either Protocol Fx-006 or Fx-1A-201.
• Male or female subjects with ATTR-PN who had not undergone liver or heart transplantation at time of enrollment.
• If female, subject was post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control

Key Exclusion criteria:

• Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs)
• Pregnant or breast feeding female subjects.
• Clinically significant medical condition that, in the opinion of the investigator, would place the subject at an increased risk to participate in the study.
• An alanine aminotransferase (ALT) and aspartate aminotransferase (AST) value >3 × upper limit of normal (ULN) that, in the medical judgment of the investigator, was due to reduced liver function or active liver disease.
• 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 study drug.

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

Argentina

FLENI

Ciudad Autonoma de Buenos aires, Argentina, C1428AQK

Brazil

Hospital Universitário Clementino Fraga Filho -HUCFF Universidade Federal do Rio de Janeiro

Rio de Janeiro, RJ, Brazil, CEP 21941-913

France

CHU Henri Mondor

Creteil cedex, France, 94010

Germany

Universitatsklinikum Muenster

Muenster, Germany, 48149

Italy

Centro per lo Studio e la Cura delle Amiloidosi Sistemiche IRCCS - Policlinico San Matteo

Pavia, Italy, 27100

Dipartimento di Neurofisiopatologia

Pavia, Italy, 27100

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy, 27100

IRCCS

Pavia, Italy, 27100

Portugal

Centro Hospitalar Lisboa Norte, EPE- Hospital de Santa Maria

Lisboa, Portugal, 1649-028

Unidade Clinica de Paramiloidose Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António

Porto, Portugal, 4099-001

Sweden

Norrlands University Hospital

Umea, Sweden, 90185

Umea University Hospital

Umea, Sweden, 90187

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Merlini G, Coelho T, Waddington Cruz M, Li H, Stewart M, Ebede B. Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years. Neurol Ther. 2020 Feb 27. doi: 10.1007/s40120-020-00180-w. [Epub ahead of print]

Huber P, Flynn A, Sultan MB, Li H, Rill D, Ebede B, Gundapaneni B, Schwartz JH. A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy. Amyloid. 2019 Dec;26(4):203-209. doi: 10.1080/13506129.2019.1643714. Epub 2019 Jul 27.

Amass L, Li H, Gundapaneni BK, Schwartz JH, Keohane DJ. Influence of baseline neurologic severity on disease progression and the associated disease-modifying effects of tafamidis in patients with transthyretin amyloid polyneuropathy. Orphanet J Rare Dis. 2018 Dec 17;13(1):225. doi: 10.1186/s13023-018-0947-7.

Barroso FA, Judge DP, Ebede B, Li H, Stewart M, Amass L, Sultan MB. Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years. Amyloid. 2017 Sep;24(3):194-204. doi: 10.1080/13506129.2017.1357545. Epub 2017 Jul 31.

Waddington Cruz M, Amass L, Keohane D, Schwartz J, Li H, Gundapaneni B. Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy. Amyloid. 2016 Sep;23(3):178-183. Epub 2016 Aug 5.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00925002
• Other Study ID Numbers: FX1A-303; B3461023 ( Other Identifier: Alias Study Number ); 2009-011535-12 ( EudraCT Number )
• First Posted: June 19, 2009
• Last Update Posted: April 28, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases