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| ID | Type | Description | Link |
|---|---|---|---|
| B3461020 |
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This study will examine whether Fx-1006A is effective in halting the progression of Familial Amyloid Polyneuropathy (FAP).
Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP.
The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience.
This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.
Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP.
The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience.
This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1. | Experimental | Fx-1006A |
|
| 2. | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fx-1006A | Drug | Fx-1006A 20mg or matched placebo once daily (at the same time each day) for a period of 18 Months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18 | Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than[<] 2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment. | Month 18 |
| Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18 | Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life. | Baseline, Month 18 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18 | NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeff Packman | FoldRx Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MGH Neuropathy Laboratory | Boston | Massachusetts | 02114 | United States | ||
| FLENI-Hepatology and Organ Transplant Dept. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32107748 | Derived | 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. | |
| 31353964 | Derived |
| Label | URL |
|---|---|
| Amyloidosis, Transthyretin-Related | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Tafamidis | Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months. |
| FG001 | Placebo | Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tafamidis | Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months. |
| BG001 | Placebo | Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Out of a total of 128 participants, baseline characteristic (Age) was available for only 125 participants who were included in intent-to-treat (ITT) population. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18 | Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than[<] 2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment. | ITTset:randomized participants received atleast(>=)1 dose of study drug, had >=1 post-baseline efficacy assessment for NIS-LL,Norfolk Quality of Life-Diabetic Neuropathy(QOL-DN) or discontinued study due to death/liver transplant(LT).Last-observation-carried-forward(LOCF) used;participant who discontinued due to death/LT was set non-responder. | Posted | Number | 95% Confidence Interval | percentage of participants | Month 18 |
|
Not provided
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tafamidis | Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 10.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 10.0 | Non-systematic Assessment |
Instead of the intended endpoint 'heat pain and cooling threshold', results of 'summated 3 score for small nerve fiber function' were reported.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Not provided
| ID | Term |
|---|---|
| D028227 | Amyloid Neuropathies, Familial |
| D000544 | Alzheimer Disease |
| D011115 | Polyneuropathies |
| D000686 | Amyloidosis |
| ID | Term |
|---|---|
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D009422 | Nervous System Diseases |
| D017772 | Amyloid Neuropathies |
Not provided
Not provided
| ID | Term |
|---|---|
| C547076 | tafamidis |
Not provided
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| Placebo | Drug | Fx-1006A 20mg or matched placebo once daily (at the same time each day) for a period of 18 Months |
|
| Baseline, Month 6, 12, 18 |
| Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12 | Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to <2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0 (normal) to 4 (paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment. | Month 6, 12 |
| Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12 | Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life. | Baseline, Month 6, 12 |
| Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 | Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7:scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale: 0=no problem, 4=severe problem (except item 32: -2=much better, 0=about same, 2=much worse). Norfolk QOL-DN summarized in 5 domains(score range):physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptoms(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12); higher score=greater impairment, for each. Total score=-2 to138(higher score=worse QOL). | Baseline, Month 6, 12, 18 |
| Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18 | Summated 7 score: composite score included five Nerve Conduction Studies (NCS) attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with Vibration Detection Threshold (VDT) obtained in great toes, and Heart Rate Response to Deep Breathing (HRDB) value. Score was determined through reference to normal values for age, sex and height. Total score range= -26 to 26, where higher score=worse nerve function. | Baseline, Month 6, 12, 18 |
| Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18 | Summated 3 Nerve Tests Small Fiber Normal Deviates Score (NTSFnds) included cooling threshold for the lower limbs, heat pain threshold for the lower limbs and HRDB. Total score range= -11.2 to 11.2, where higher score=worse nerve function. | Baseline, Month 6, 12, 18 |
| Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18 | BMI was calculated by weight divided by height squared. mBMI was calculated by multiplying BMI by serum albumin levels to compensate for edema formation associated with malnutrition. A progressive decline in mBMI indicated worsening of disease severity. | Baseline, Month 6, 12, 18 |
| Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer | TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI. | Week 8, Month 6, 12, 18 |
| Ciudad de Buenos Aires |
| Buenos Aires |
| C1428AQK |
| Argentina |
| Hospital Universitário Prof. Clementino Fraga Filho-UFRJ | Rio de Janeiro | Southeast | Cep 21945-560 | Brazil |
| CHU de Bicetre | Le Kremlin-Bicêtre | Île-de-France Region | 94275 | France |
| Universitatsklinikum Munster, Transplant Hepatology | Münster | North Rhine-Westphalia | 48149 | Germany |
| Serviço de Neurologia-Hospital de Santa Maria | Lisbon | Lisbon District | 1649-035 | Portugal |
| Unidade Clinica de Paramiloidose-Hospital Santo Antonio | Porto | Norte | 4099-001 | Portugal |
| Hospital Clinic de Barcelona | Barcelona | Catalonia | 08036 | Spain |
| Umea University Hospital | Umeå | Västerbotten County | SE-901 85 | Sweden |
| Kings College Hospital | London | London | SE5 9RS | United Kingdom |
| 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. |
| 30558645 | Derived | 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. |
| 29115008 | Derived | Gundapaneni BK, Sultan MB, Keohane DJ, Schwartz JH. Tafamidis delays neurological progression comparably across Val30Met and non-Val30Met genotypes in transthyretin familial amyloid polyneuropathy. Eur J Neurol. 2018 Mar;25(3):464-468. doi: 10.1111/ene.13510. Epub 2017 Dec 26. |
| 28393570 | Derived | Keohane D, Schwartz J, Gundapaneni B, Stewart M, Amass L. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Mar;24(1):30-36. doi: 10.1080/13506129.2017.1301419. Epub 2017 Apr 10. |
| 27494299 | Derived | 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. |
| Negative genotype |
|
| Liver transplantation |
|
| BG002 | Total | Total of all reporting groups |
| Number |
| participants |
|
| Sex: Female, Male | Out of a total of 128 participants, baseline characteristic (Gender) was available for only 125 participants who were included in ITT population. | Count of Participants | Participants |
|
| OG000 | Tafamidis | Tafamidis (Fx-1006A) 20 milligram (mg) capsule orally once daily for 18 months. |
| OG001 | Placebo | Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months. |
|
|
| Primary | Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18 | Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life. | ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death or LT. LOCF method was used. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Month 18 |
|
|
|
| Secondary | Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18 | NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment. | ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death/LT. 'n' = those participants who were evaluable for this measure at given time point for each group respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Month 6, 12, 18 |
|
|
|
| Secondary | Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12 | Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to <2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0 (normal) to 4 (paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment. | ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death/LT. LOCF method was used; participant who discontinued due to death/LT was set non-responder. | Posted | Number | 95% Confidence Interval | percentage of participants | Month 6, 12 |
|
|
|
| Secondary | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12 | Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life. | ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death/LT. 'n' = those participants who were evaluable for this measure at given time point for each group respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Month 6, 12 |
|
|
|
| Secondary | Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18 | Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7:scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale: 0=no problem, 4=severe problem (except item 32: -2=much better, 0=about same, 2=much worse). Norfolk QOL-DN summarized in 5 domains(score range):physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptoms(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12); higher score=greater impairment, for each. Total score=-2 to138(higher score=worse QOL). | ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death or LT. 'n' = those participants who were evaluable for this measure at given time points for each group respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Month 6, 12, 18 |
|
|
|
| Secondary | Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18 | Summated 7 score: composite score included five Nerve Conduction Studies (NCS) attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with Vibration Detection Threshold (VDT) obtained in great toes, and Heart Rate Response to Deep Breathing (HRDB) value. Score was determined through reference to normal values for age, sex and height. Total score range= -26 to 26, where higher score=worse nerve function. | ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death/LT. 'n' = those participants who were evaluable for this measure at given time points for each group respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Month 6, 12, 18 |
|
|
|
| Secondary | Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18 | Summated 3 Nerve Tests Small Fiber Normal Deviates Score (NTSFnds) included cooling threshold for the lower limbs, heat pain threshold for the lower limbs and HRDB. Total score range= -11.2 to 11.2, where higher score=worse nerve function. | ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death/LT. 'n' = those participants who were evaluable for this measure at given time points for each group respectively. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Month 6, 12, 18 |
|
|
|
| Secondary | Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18 | BMI was calculated by weight divided by height squared. mBMI was calculated by multiplying BMI by serum albumin levels to compensate for edema formation associated with malnutrition. A progressive decline in mBMI indicated worsening of disease severity. | ITT population included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline efficacy assessment for NIS-LL and Norfolk QOL-DN or discontinued study due to death/LT. 'n' = those participants who were evaluable for this measure at given time points for each group respectively. | Posted | Mean | Standard Deviation | (kilogram/square meter)*(gram/liter) | Baseline, Month 6, 12, 18 |
|
|
|
| Secondary | Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer | TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI. | ITT population. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure. 'n' = those participants who were evaluable for this measure at given time points for each group respectively. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 8, Month 6, 12, 18 |
|
|
|
| 6 |
| 65 |
| 57 |
| 65 |
| EG001 | Placebo | Placebo, matched to tafamidis (Fx-1006A) 20 mg capsule, orally once daily for 18 months. | 5 | 63 | 56 | 63 |
| Conduction disorder | Cardiac disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Cardiac amyloidosis | Cardiac disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Catheter site phlebitis | General disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Localised infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Lymphangitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Burns third degree | Injury, poisoning and procedural complications | MedDRA 10.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Hypertensive emergency | Vascular disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Atrioventricular block first degree | Cardiac disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Lacrimation decreased | Eye disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Punctate keratitis | Eye disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Vaginal infection | Infections and infestations | MedDRA 10.0 | Non-systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 10.0 | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 10.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028226 | Amyloidosis, Familial |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D057165 | Proteostasis Deficiencies |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D024801 | Tauopathies |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| Change at Month 12 (n=49, 50) |
|
| Change at Month 18 (n=48, 47) |
|
| Change at Month 12 (n=49, 50) |
|
| Baseline: symptoms(n=64,61) |
|
| Baseline: small fiber neuropathy(n=64,61) |
|
| Baseline: autonomic neuropathy(n=64,61) |
|
| Change at Month 6: physical functioning(n=60,57) |
|
| Change at Month 6: ADLs(n=60,57) |
|
| Change at Month 6: symptoms(n=60,56) |
|
| Change at Month 6: small fiber neuropathy(n=60,57) |
|
| Change at Month 6: autonomic neuropathy(n=60,57) |
|
| Change at Month 12: physical functioning(n=49,50) |
|
| Change at Month 12: ADLs(n=49,50) |
|
| Change at Month 12: symptoms(n=49,49) |
|
| Change at Month 12:small fiber neuropathy(n=49,50) |
|
| Change at Month 12: autonomic neuropathy(n=49,50) |
|
| Change at Month 18: physical functioning(n=48,47) |
|
| Change at Month 18: ADLs(n=48,47) |
|
| Change at Month 18: symptoms(n=48,47) |
|
| Change at Month 18:small fiber neuropathy(n=48,47) |
|
| Change at Month 18: autonomic neuropathy(n=48,47) |
|
| Change at Month 12 (n=48, 50) |
|
| Change at Month 18 (n=48, 46) |
|
| Change at Month 12 (n=48, 50) |
|
| Change at Month 18 (n=48, 46) |
|
| Change at Month 12 (n=49, 50) |
|
| Change at Month 18 (n=49, 46) |
|
| Month 12 (n=48, 50) |
|
| Month 18 (n=48, 44) |
|