Clinical trial NCT00925002: Safety And Efficacy Evaluation Of Fx-1006A In Subjects With Transthyretin Amyloidosis
Official title: OPEN-LABEL SAFETY AND EFFICACY EVALUATION OF FX-1006A IN SUBJECTS WITH TRANSTHYRETIN (TTR) AMYLOIDOSIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ATTR-PN
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-06-19
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Primary purpose: TREATMENT

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for the treatment of ATTR-PN in their respective country and access to prescription tafamidis, subjects may have been withdrawn from the study.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.


Eligibility 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.

Primary outcomes:
measure: Val30Met Group: Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Baseline
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005)
measure: Val30Met Group: Change From B3461020 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 30
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005), Month 30
measure: Val30Met Group: Change From B3461020 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 66
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005), Month 66
measure: NonVal30Met Group: Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Baseline
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201)
measure: NonVal30Met Group: Change From B3461022 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 12
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201), Month 12
measure: NonVal30Met Group: Change From B3461022 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 60
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201), Month 60
measure: Val30Met Group: Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Baseline
timeFrame: Baseline of B3461020 (Fx-005)
measure: Val30Met Group: Change From B3461020 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 30
timeFrame: Baseline of B3461020 (Fx-005), Month 30
measure: Val30Met Group: Change From B3461020 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 66
timeFrame: Baseline of B3461020 (Fx-005), Month 66
measure: NonVal30Met Group: Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Baseline
timeFrame: Baseline of B3461022 (Fx1A-201)
measure: NonVal30Met Group: Change From B3461022 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 12
timeFrame: Baseline of B3461022 (Fx1A-201), Month 12
measure: NonVal30Met Group: Change From B3461022 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 60
timeFrame: Baseline of B3461022 (Fx1A-201), Month 60
measure: Val30Met Group: Karnofsky Performance Scale (KPS) Score at Month 30
timeFrame: Month 30 (Baseline of B3461023)
measure: Val30Met Group: Karnofsky Performance Scale (KPS) Score at Month 66
timeFrame: Month 66 (Month 36 of B3461023)
measure: NonVal30Met Group: Karnofsky Performance Scale (KPS) Score at Baseline
timeFrame: Baseline of B3461022 (Fx1A-201)
measure: NonVal30Met Group: Change From B3461022 Baseline in Karnofsky Performance Scale (KPS) Score at Month 12
timeFrame: Baseline of B3461022 (Fx1A-201), Month 12
measure: NonVal30Met Group: Change From B3461022 Baseline in Karnofsky Performance Scale (KPS) Score at Month 60
timeFrame: Baseline of B3461022 (Fx1A-201), Month 60
measure: Val30Met Group: Number of Participants by Ambulation Stage at Baseline
timeFrame: Baseline of B3461020 (Fx-005)
measure: Val30Met Group: Number of Participants by Ambulation Stage at Month 30
timeFrame: Month 30
measure: Val30Met Group: Number of Participants by Ambulation Stage at Month 66
timeFrame: Month 66
measure: NonVal30Met Group: Number of Participants by Ambulation Stage at Baseline
timeFrame: Baseline of B3461022 (Fx1A-201)
measure: NonVal30Met Group: Number of Participants by Ambulation Stage at Month 12
timeFrame: Month 12
measure: NonVal30Met Group: Number of Participants by Ambulation Stage at Month 60
timeFrame: Month 60
Secondary outcomes:
measure: Val30Met Group: Change From B3461020 Baseline in NIS-LL Score at Month 6, 12, 18, 24, 42, 54, 78, 90, 102, 114 and 126
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005), Month 6, 12, 18, 24, 42, 54, 78, 90, 102, 114 and 126
measure: Val30Met Group: NIS-LL Subscales Scores: Muscle Weakness (MW), MW-Hip, MW-Knee, MW-Ankle, MW-Toe, NIS-LL Reflexes, NIS-LL Sensory at Baseline
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005)
measure: Val30Met Group: Change From B3461020 Baseline in NIS-LL Subscales Scores: Muscle Weakness (MW), MW-Hip, MW-Knee, MW-Ankle, MW-Toe, NIS-LL Reflexes, NIS-LL Sensory at Month 6, 12, 18, 24, 30, 42, 54, 66, 78, 90, 102, 114 and 126
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461020 (Fx-005), Month 6, 12, 18, 24, 30, 42, 54, 66, 78, 90, 102, 114 and 126
measure: NonVal30Met Group: Change From B3461022 Baseline in NIS-LL Score at Month 6, 24, 36, 48, 72, 84, 96, 108 and 120
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201), 6, 24, 36, 48, 72, 84, 96, 108 and 120
measure: NonVal30Met Group: NIS-LL Subscales Scores: Muscle Weakness (MW), MW-Hip, MW-Knee, MW-Ankle, MW-Toe, NIS-LL Reflexes, NIS-LL Sensory at Baseline
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201)
measure: NonVal30Met Group: Change From B3461022 Baseline in NIS-LL Subscales Scores: Muscle Weakness (MW), MW-Hip, MW-Knee, MW-Ankle, MW-Toe, NIS-LL Reflexes, NIS-LL Sensory at Month 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
timeFrame: Baseline (i.e. last measurement prior to first dose) of B3461022 (Fx1A-201), Month 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
measure: Val30Met Group: Change From B3461020 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 6, 12, 18, 24, 42, 54, 78, 90, 102, 114, 126, 138
timeFrame: Baseline of B3461020 (Fx-005), Month 6, 12, 18, 24, 42, 54, 78, 90, 102, 114, 126, 138
measure: Val30Met Group: TQOL Subscale Scores: Symptom, ADLs, Physical Functioning/Large Fiber Neuropathy, Small Fiber Neuropathy, Autonomic Neuropathy Assessed Using Norfolk QOL-DN at Baseline
timeFrame: Baseline of B3461020 (Fx-005)
measure: Val30Met:Change From Baseline in TQOL Subscale Scores:Symptom, ADLs, Physical Functioning/Large Fiber Neuropathy, Small Fiber Neuropathy, Autonomic Neuropathy Assessed Using Norfolk QOL-DN at Month 6, 12, 18, 24, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138
timeFrame: Baseline of B3461020 (Fx-005), Month 6, 12, 18, 24, 30, 42, 54, 66, 78, 90, 102, 114, 126 and 138
measure: NonVal30Met Group: Change From B3461022 Baseline in Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Month 6, 24, 36, 48, 72, 84, 96, 108, 120
timeFrame: Baseline of B3461022 (Fx1A-201), Month 6, 24, 36, 48, 72, 84, 96, 108, 120
measure: NonVal30Met Group: TQOL Subscale Scores: Symptom, ADLs, Physical Functioning/Large Fiber Neuropathy, Small Fiber Neuropathy, Autonomic Neuropathy Assessed Using Norfolk QOL-DN at Baseline
timeFrame: Baseline of B3461022 (Fx1A-201)
measure: NonVal30Met Group: Change From Baseline in TQOL Subscale Scores: Symptom, ADLs, Physical Functioning/Large Fiber Neuropathy, Small Fiber Neuropathy, Autonomic Neuropathy Assessed Using Norfolk QOL-DN at Month 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120
timeFrame: Baseline of B3461022 (Fx1A-201), Month 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
measure: Val30Met Group: Karnofsky Performance Scale (KPS) Score at Month 42, 54, 78, 90, 102, 114, 126 and 138
timeFrame: Baseline of B3461023, Month 42, 54, 78, 90, 102, 114, 126 and 138
measure: NonVal30Met Group: Change From B3461022 Baseline in Karnofsky Performance Scale (KPS) Score at Month 6, 24, 36, 48, 72, 84, 96, 108 and 120
timeFrame: Baseline of B3461022, Month 6, 24, 36, 48, 72, 84, 96, 108 and 120
measure: Val30Met Group: Number of Participants by Ambulation Stage at Week 12, Month 6, 9, 12, 18, 21, 24, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129
timeFrame: Week 12, Month 6, 9, 12, 18, 21, 24, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126 and 129
measure: NonVal30Met Group: Number of Participants by Ambulation Stage at Month 3, 6, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129
timeFrame: Month 3, 6, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126 and 129
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious AEs
timeFrame: From Baseline (i.e., Day 0 of B3461023) up to 10 years
measure: Number of Participants With Abnormality in Physical Examinations
timeFrame: From Baseline (i.e., Day 0 of B3461023) up to 10 years
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: From Baseline (i.e., Day 0 of B3461023) up to 10 years
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: From Baseline (i.e., Day 0 of B3461023) up to 10 years
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
timeFrame: From Baseline (i.e., Day 0 of B3461023) up to 10 years
measure: Number of Participants With Any Concomitant Medications Usage
timeFrame: From Baseline (i.e., Day 0 of B3461023) up to 10 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Ciudad Autonoma de Buenos aires
country: Argentina
facility: FLENI
city: Rio De Jameiro
country: Brazil
facility: Hospital Universitário Clementino Fraga Filho -HUCFF Universidade Federal do Rio de Janeiro
state: R.j.
city: Creteil
country: France
facility: Centre d'Investigation Clinique
city: Muenster
country: Germany
facility: Universitatsklinikum Muenster
city: Pavia
country: Italy
facility: Centro per lo Studio e la Cura delle Amiloidosi Sistemiche IRCCS - Policlinico San Matteo
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte, EPE- Hospital de Santa Maria
city: Porto
country: Portugal
facility: Unidade Clinica de Paramiloidose Centro Hospitalar do Porto, EPE - Hospital Geral de Santo António
city: Umea
country: Sweden
facility: FAP-Teamet Familjar Amyloidos
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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 Jun;9(1):105-115. doi: 10.1007/s40120-020-00180-w. Epub 2020 Feb 27.
citation: 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.
citation: 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.
citation: 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.
citation: 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. doi: 10.1080/13506129.2016.1207163. Epub 2016 Aug 5.