Retrospective Study Collecting Neurological Follow-up of Hereditary Transthyretin Amyloidosis (ATTRv) Patients Included in B3461028 and B3461045.
- Conditions
- Hereditary Transthyretin Amyloidosis (ATTRv)Polyneuropathy
- Interventions
- Registration Number
- NCT05560555
- Lead Sponsor
- Pfizer
- Brief Summary
A study of patients with hereditary transthyretin amyloidosis (ATTRv) and wild-type transthyretin amyloidosis (ATTRwt) that have been enrolled in B3461028 and B3461045 studies in Spain - exposed to tafamidis 61mg for ≥12 months with polyneuropathy (PN) have kept going to their multisystemic follow-ups (neuro/ophthalmo/gastrointestinal) ≥12 months.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5
- Treatment with tafamidis 61 mg ≥ 12 months
- Neurological follow up ≥ 12 months
- Diagnosis of transthyretin amyloidosis with polyneuropathy (ATTR-PN) based on one of the following:
- Amplitude reduction in, at least, 2 nerves under normal value, excluding median nerve OR 50% amplitude reduction in, at least, 2 nerves on the basal value of the patient, excluding median nerve OR 2 abnormal tests detecting thin fibers alterations (through Sudo scan, RR Interval analysis, etc..)
- Treatment with tafamidis 61 mg < 12 months
- Neurological follow up < 12 months
- Other diagnosis for polyneuropathy
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Retrospective cohort ATTRv and ATTRwt patients enrolled in B3461028 and B3461045 studies in Spain Tafamidis -
- Primary Outcome Measures
Name Time Method Change in Neuropathy Impairment Score (NIS) at Month 12 for ATTRv Baseline and Month 12 (data collected and analyzed over 22 days) NIS (Neuropathy Impairment Score) is a clinically important, sensitive measure of individual neurological function, assessing sensory function, reflexes, and muscle weakness. NIS score ranged from 0 to 244, with higher score indicating greater disability or impairment. The rate of change was calculated from last follow-up.
- Secondary Outcome Measures
Name Time Method Change in Familial Amyloid Polyneuropathy Specific Rasch-Built Overall Disability Scale (FAP-RODs) for ATTRv Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) FAP-RODS is a questionnaire that assessed the effect of neuropathy on daily activities. FAP-RODS total score ranged from 0 to 68; where, 0=Lower ability to perform daily activities and 68=Greater ability to perform daily activities.
Number of Participants According to Familiar Amyloidotic Polyneuropathy Stage (FAP) for ATTRv Month 18, 24 and 30 months after the start of treatment (data collected and analyzed over 22 days) FAP is a stage system based on symptom severity and disease progression. FAP stages included: Asymptomatic; Free ambulation (walking without support): stage 1; Supportive ambulation (walking with support): stage 2; Wheelchair-bound or bedridden: stage 3.
Change in NIS for ATTRv Baseline, Month 6, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) NIS (Neuropathy Impairment Score) is a clinically important, sensitive measure of individual neurological function, assessing sensory function, reflexes, and muscle weakness. NIS score ranged from 0 to 244, with higher score indicating greater disability or impairment. The rate of change was calculated from last follow-up.
Change in COMPASS-31 for ATTRv Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) COMPASS-31 (Composite Autonomic Symptom Score 31) is a questionnaire designed to assess the severity and functional ability in participants with autonomic dysfunction. COMPASS-31 total score ranged from 0 to 100; where 0=Lesser severity of dysautonomia and 100=Greater severity of dysautonomia.
Change in Neuropathy Impairment Score - Lower Limbs (NIS-LL) for ATTRv Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) NIS-LL (Neuropathy Impairment Score Lower Limbs) is a clinically important, sensitive measure of neurological function in individuals, assessing sensory function, reflexes, and muscle weakness of the lower limbo. NÍS-LL assessed muscle weakness, reflexes, sensation. Each item is scored separately for left and right limbs. Components of muscle weakness:0(normal) to4(paralysis), higher score=more weakness; reflexes, sensation:0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=more impairment. The rate of change was calculated from last follow-up.
Change in Norfolk Quality of Life- Diabetic Neuropathy (Norfolk QOL-DN) for ATTRv Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) Norfolk Quality of Life Questionnaire for Diabetic Neuropathy is a standardized and validated instrument that assesses the effect of polyneuropathy on the functionality and quality of life of the individual. Norfolk QOL-DN: 35-item participant-rated questionnaire is 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= -4 to 138, where higher score=worse quality of life.
Percentage of Participants Who do Not Have Stage Progression in the PND Score for ATTRv From Baseline to Month 30 (data collected and analyzed over 22 days) PND is a staging system that assess the degree of neuropathic dysfunction and its impact on ambulation. PND stages included: Asymptomatic; Stage I: Sensory disturbances, normal gait; Stage II: Sensory disturbances, altered gait not requiring support; IIIA: Gait requiring one support; IIIB: Gait requiring two supports; IV: Wheelchair or bedside. Participants who did not change to higher stages compared to the start of treatment was reported as Unchanged and those who progressed to higher stages were reported under Staging up.
Number of Participants With Symptoms of Autonomic Neuropathy Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Number of participants with symptoms of autonomic neuropathy including impaired sweating, sexual dysfunction, orthostatic hypotension were reported in this outcome measure.
Number of Participants With Symptoms of Peripheral Neuropathy At baseline (data collected and analyzed over 22 days) Number of participants with symptoms of peripheral neuropathy (allodynia and paresthesia) were reported in this outcome measure.
Percentage of Responders to Treatment for ATTRv Month 12 (data collected and analyzed over 22 days) Percentage of responders to treatment at Month 12 was defined as participants who achieved the change from baseline of less than 4 points in the NIS and participants who achieved the change from baseline of less than 2 points in the NIS-LL were reported in this outcome measure.
Ulnar/Sural Sensory Nerve Action Potential Amplitude (SNAP) for ATTRv Month 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb.
Change in NIS for ATTRwt Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) NIS (Neuropathy Impairment Score) was a clinically important, sensitive measure of individual neurological function, assessing sensory function, reflexes, and muscle weakness. NIS score ranged from 0 to 244, with higher score indicating greater disability or impairment. The rate of change was calculated from last follow-up.
Change in NIS-LL for ATTRwt Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) NIS-LL (Neuropathy Impairment Score Lower Limbs) was clinically important, sensitive measure of neurological function in individuals, assessing sensory function, reflexes, and muscle weakness of the lower limbo. NÍS-LL assessed muscle weakness, reflexes, sensation. Each item scored separately for left and right limbs. Components of muscle weakness:0(normal) to4(paralysis), higher score=more weakness; reflexes, sensation:0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=more impairment. The rate of change was calculated from last follow-up.
Number of Participants With R-R Interval Variability for ATTRv Month 18, 24 and 30 (data collected and analyzed over 22 days) Number of participants with R-R interval variability (altered/unaltered) was reported in this outcome measure.
Number of Participants With R-R Interval Variability for ATTRwt Month 18, 24 and 30 (data collected and analyzed over 22 days) Number of participants with R-R interval variability (altered/unaltered) was reported in this outcome measure.
mBMI for ATTRwt Month 18, 24 and 30 after start of treatment (data collected and analysed over 22 days) BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2).
Ulnar/Sural SNAP Score for ATTRwt Month 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb.
Ulnar/Peroneal CMAP Score for ATTRwt Month 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Peroneal motor nerve compound muscle action potential amplitude (in millivolts) was measured using electromyography of the left lower limb.
Number of Participants With Carpal Tunnel Syndrome At baseline (data collected and analyzed over 22 days) Number of participants with carpal tunnel syndrome were reported in this outcome measure.
Number of Participants With Lumbar Stenosis At baseline (data collected and analyzed over 22 days) Number of participants with lumbar stenosis were reported in this outcome measure.
Modified Body Mass Index (mBMI) for ATTRv Month 18, 24 and 30 after start of treatment (data collected and analysed over 22 days) BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). mBMI was calculated by multiplying BMI by serum albumin levels \[gram/liter (g/L)\].
Ulnar/Peroneal Compound Muscle Action Potential Amplitude (CMAP) for ATTRv Month 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Peroneal motor nerve compound muscle action potential amplitude was measured using electromyography of the left lower limb.
Percentage of Participants Who do Not Have Stage Progression in the PND Score for ATTRwt From Baseline to Month 30 (data collected and analysed over 22 days) PND was a simple staging system according to the degree of neuropathic dysfunction and its impact on ambulation. PND stages included: Asymptomatic: I Sensory disturbances, normal gait: II Sensory disturbances, altered gait not requiring support: IIIA Gait requiring one support: IIIB Gait requiring two supports: IV Wheelchair or bedside). Participants who did not change to higher stages compared to the start of treatment was reported as Unchanged and those who progressed to higher stages were reported under Staging up.
Percentage of Responders to Treatment for ATTRwt Month 12 (data collected and analyzed over 22 days) Percentage of responders to treatment was defined as participants who achieved the change from baseline of less than 4 points in the NIS and participants who achieved the change from baseline of less than 2 points in the NIS-LL were reported in this outcome measure.
Change in Norfolk QOL-DN for ATTRwt Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) Norfolk Quality of Life Questionnaire for Diabetic Neuropathy was a standardized and validated instrument that assesses the effect of polyneuropathy on the functionality and quality of life of the individual. 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= -4 to 138, where higher score=worse quality of life.
Change in COMPASS-31 for ATTRwt Baseline, Month 6, 12, 18, 24 and 36 after treatment initiation COMPASS-31 (Composite Autonomic Symptom Score 31) was a questionnaire designed to assess the severity and functional ability in participants with autonomic dysfunction. COMPASS-31 total score ranged from 0 to 100; where 0=Lesser severity of dysautonomia and 100=Greater severity of dysautonomia.
Change in FAP-RODs for ATTRwt Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days) FAP-RODS is a questionnaire that assessed the effect of neuropathy on daily activities. FAP-RODS total score ranged from 0 to 68; where, 0=Lower ability to perform daily activities and 68=Greater ability to perform daily activities.
Number of Participants According to FAP Stage for ATTRwt Month 18, 24 and 30 months after the start of treatment (data collected and analyzed over 22 days) FAP stage is a staging system based on symptom severity and disease progression. FAP stages included: Asymptomatic; Free ambulation (Walking without support): stage 1; Supportive ambulation (Walking with support): stage 2; Wheelchair-bound or bedridden: stage 3.
Number of Participants With Gastrointestinal Disturbances Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Number of participants with gastrointestinal disturbances were reported in this outcome measure.
Number of Participants With Unintentional Weight Loss Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Number of participants with unintentional weight loss were reported in this outcome measure.
Number of Participants With Urological Disturbances Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Number of participants with urological disturbances were reported in this outcome measure.
Number of Participants With Ophthalmological Disturbances Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Number of participants with ophthalmological disturbances were reported in this outcome measure.
Number of Participants With Central Nervous System (CNS) Disturbances Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days) Number of participants with CNS disturbances were reported in this outcome measure.
Trial Locations
- Locations (3)
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Spain