Phase 3
Completed N=93
Safety And Efficacy Evaluation Of Fx-1006A In Subjects With Transthyretin Amyloidosis
ATTR-PN
Source: ClinicalTrials.gov NCT00925002 ↗
Enrolled (actual)
93
Serious AEs
26.9%
Results posted
Jul 2021
Primary outcomePrimary: Val30Met Group: Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Baseline — 6.8; 11.6 units on a scale
◆ Published Evidence
Highly cited
110citations · ~12 / year
Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years.
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for the treatment of ATTR-PN in their respective country and access to prescription tafamidis, subjects may have been withdrawn from the study.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.
Linked Publications (5)
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Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years.
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Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy.
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Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years.
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A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy.
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Influence of baseline neurologic severity on disease progression and the associated disease-modifying effects of tafamidis in patients with transthyretin amyloid polyneuropathy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Val30Met Group: Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Baseline |
6.8; 11.6 | — |
| PRIMARY Val30Met Group: Change From B3461020 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 30 |
3.8; 6.4 | — |
| PRIMARY Val30Met Group: Change From B3461020 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 66 |
7.8; 11.3 | — |
| PRIMARY NonVal30Met Group: Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Baseline |
31.1 | — |
| PRIMARY NonVal30Met Group: Change From B3461022 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 12 |
2.5 | — |
| PRIMARY NonVal30Met Group: Change From B3461022 Baseline in Neuropathy Impairment Score Lower Limb (NIS-LL) Score at Month 60 |
12.0 | — |
| PRIMARY Val30Met Group: Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Baseline |
24.1; 29.9 | — |
| PRIMARY 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 |
0.1; 4.5 | — |
| PRIMARY 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 |
5.2; 5.3 | — |
| PRIMARY NonVal30Met Group: Total Quality of Life (TQOL) Score Assessed Using Norfolk Quality of Life for Diabetic Neuropathy (QOL-DN) Questionnaire at Baseline |
53.9 | — |
| PRIMARY 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 |
0.9 | — |
| PRIMARY 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 |
12.9 | — |
| PRIMARY Val30Met Group: Karnofsky Performance Scale (KPS) Score at Month 30 |
83.8; 80.3 | — |
| PRIMARY Val30Met Group: Karnofsky Performance Scale (KPS) Score at Month 66 |
85.9; 78.7 | — |
| PRIMARY NonVal30Met Group: Karnofsky Performance Scale (KPS) Score at Baseline |
72.2 | — |
| PRIMARY NonVal30Met Group: Change From B3461022 Baseline in Karnofsky Performance Scale (KPS) Score at Month 12 |
-3.1 | — |
| PRIMARY NonVal30Met Group: Change From B3461022 Baseline in Karnofsky Performance Scale (KPS) Score at Month 60 |
-12.4 | — |
| PRIMARY Val30Met Group: Number of Participants by Ambulation Stage at Baseline |
37; 36; 0; 0; 0; 0 | — |
| PRIMARY Val30Met Group: Number of Participants by Ambulation Stage at Month 30 |
37; 34; 0; 1; 1; 1 | — |
| PRIMARY Val30Met Group: Number of Participants by Ambulation Stage at Month 66 |
22; 15; 2; 3; 0; 0 | — |
| PRIMARY NonVal30Met Group: Number of Participants by Ambulation Stage at Baseline |
7; 5; 0 | — |
| PRIMARY NonVal30Met Group: Number of Participants by Ambulation Stage at Month 12 |
7; 5; 1 | — |
| PRIMARY NonVal30Met Group: Number of Participants by Ambulation Stage at Month 60 |
1; 6; 0 | — |
| SECONDARY Val30Met Group: Change From B3461020 Baseline in NIS-LL Score at Month 6, 12, 18, 24, 42, 54, 78, 90, 102, 114 and 126 |
1.4; 0.6; 1.4; 3.6; 2.6; 4.4 | — |
| SECONDARY 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 |
2.1; 4.2; 0.2; 0.3; 0.2; 0.4 | — |
| SECONDARY 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 |
0.6; 0.5; 0.8; 2.4; 1.3; 3.1 | — |
| SECONDARY NonVal30Met Group: Change From B3461022 Baseline in NIS-LL Score at Month 6, 24, 36, 48, 72, 84, 96, 108 and 120 |
-0.7; 6.6; 10.9; 12.3; 14.6; 10.4 | — |
| SECONDARY 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 |
16.6; 1.6; 2.5; 5.5; 6.9; 5.6 | — |
| SECONDARY 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 |
-0.4; 2.3; 5.1; 7.3; 9.7; 8.0 | — |
| SECONDARY 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 |
-2.2; -0.5; -2.8; 5.4; -2.3; 6.4 | — |
| SECONDARY Val30Met Group: TQOL Subscale Scores: Symptom, ADLs, Physical Functioning/Large Fiber Neuropathy, Small Fiber Neuropathy, Autonomic Neuropathy Assessed Using Norfolk QOL-DN at Baseline |
6.4; 6.8; 1.4; 1.9; 12.4; 15.9 | — |
| SECONDARY 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 |
-0.2; -0.1; -0.9; 1.5; -1.1; 0.6 | — |
| SECONDARY 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 |
-4.0; 4.0; 15.8; 15.5; 16.2; 9.5 | — |
| SECONDARY NonVal30Met Group: TQOL Subscale Scores: Symptom, ADLs, Physical Functioning/Large Fiber Neuropathy, Small Fiber Neuropathy, Autonomic Neuropathy Assessed Using Norfolk QOL-DN at Baseline |
10.3; 8.4; 28.7; 4.5; 2.0 | — |
| SECONDARY 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 |
-0.8; 0.0; -0.1; 2.9; 4.1; 2.6 | — |
| SECONDARY Val30Met Group: Karnofsky Performance Scale (KPS) Score at Month 42, 54, 78, 90, 102, 114, 126 and 138 |
83.8; 81.5; 86.1; 82.1; 78.9; 81.4 | — |
| SECONDARY NonVal30Met Group: Change From B3461022 Baseline in Karnofsky Performance Scale (KPS) Score at Month 6, 24, 36, 48, 72, 84, 96, 108 and 120 |
-0.9; -5.3; -4.8; -10.6; -10.1; -3.3 | — |
| SECONDARY 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 |
37; 36; 0; 0; 0; 0 | — |
| SECONDARY 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 |
7; 5; 0; 7; 5; 0 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious AEs |
35; 33; 18; 6; 9; 10 | — |
| SECONDARY Number of Participants With Abnormality in Physical Examinations |
29; 32; 14 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities |
21; 21; 12 | — |
| SECONDARY Number of Participants With Electrocardiogram (ECG) Abnormalities |
8; 7; 6; 3; 2; 4 | — |
| SECONDARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs |
38; 37; 18 | — |
| SECONDARY Number of Participants With Any Concomitant Medications Usage |
36; 37; 17 | — |
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.
Data sourced from ClinicalTrials.gov (NCT00925002) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.