Amyloidosis
Conditions
Keywords
RNAi therapeutic, FAP, Familial Amyloid Polyneuropathy, TTR, Transthyretin, Amyloidosis
Brief summary
The purpose of this study is to evaluate the safety and efficacy of long-term dosing with ALN-TTR02 (patisiran) in participants with transthyretin (TTR) mediated amyloidosis (ATTR).
Interventions
DRUGPatisiran
Patisiran was administered IV.
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All the participants received only patisiran but divided into 3 arm groups based on administration in the parent study (placebo or patisiran in 003 \[NCT01961921\] or 004 \[NCT01960348\] studies).
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Have completed a patisiran study (i.e., completed the last efficacy visit in the parent study) and, in the opinion of the investigator, tolerated study drug * Be willing and able to comply with the protocol-required visit schedule and visit requirements and provide written informed consent
Exclusion criteria
* Any new or uncontrolled condition that could make the participant unsuitable for participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) Leading to Study Discontinuation | First dose up to 28 days after last dose of study drug (approximately 5.6 years) | AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3 | Baseline, Year 3 | The mNIS+7 is a composite measure of neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs, and cranial nerves to assess motor strength/weakness (192 points), reflexes (20 points), electrophysiologic measurement of small and large nerve fiber function (10 points), sensory testing (80 points), and postural blood pressure (2 points). The total mNIS+7 composite score is obtained by combining all the component scores, ranging from 0 (no impairment) to 304 (maximum impairment). A negative change from baseline indicates an improvement in neuropathy. |
| Change From Baseline in the NIS+7 Total Score at Week 52 | Baseline, Week 52 | The NIS+7 provides additional, objective measures of nerve fibre function and autonomic nerve function in participants with diabetic neuropathy. The NIS+7 includes the full NIS, sum of 5 nerve conduction studies (NCS) (Sural sensory nerve action potential \[SNAP\], tibial motor nerve distal latency, peroneal compound motor action potential \[CMAP\], motor nerve conduction velocity, motor nerve distal latency), vibration detection threshold, and pulse rate response to deep breathing. The total NIS+7 score is obtained by combining all the component scores, ranging from 0 (no impairment) to 270 points (maximum impairment). A positive change from baseline indicates worsening. |
| Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5 | Baseline, Year 5 | The Norfolk QoL-DN questionnaire is a standardized 47-item patient-reported outcomes measure, sensitive to the perception of the effects of diabetic neuropathy by the participant. The scores range from -4 (best possible QOL) to 136 (worst possible QOL). A negative change from baseline represents improved QOL. |
| Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5 | Baseline, Year 5 | The EQ-5D-5L is a patient-reported measure of QoL based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The overall score is rated on a scale from 0 (worst) to 1 (no impairment). Higher scores indicate a higher QoL. A negative change from baseline indicates worsening of QoL. |
| Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5 | Baseline, Year 5 | EQ-VAS measures the participant's self-rated health on a vertical scale evaluated on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Higher scores indicate a higher QOL. A negative change from baseline indicates worsening of QoL. |
| Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52 | Baseline, Week 52 | COMPASS 31 questionnaire measures autonomic symptoms in participants with neuropathy. The questionnaire consists of 31 clinically selected questions evaluating 6 autonomic domains (orthostatic intolerance, secretomotor, gastrointestinal, bladder, and pupillomotor). COMPASS 31 is measured on a scale from 0 to 100, with 100 representing maximum impairment. |
| Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5 | Baseline, Year 5 | Nutritional status of participants was evaluated using the mBMI, calculated as BMI (kilograms per square meter \[kg/m\^2\]) multiplied by the concentration of serum albumin (grams per liter \[g/L\]). A positive change from baseline indicates improvement in nutritional status. |
| Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5 | Baseline, Year 5 | The R-ODS is a 24-item patient-reported questionnaire that specifically captures activity and social participation limitations. It measures the level of disability on a scale of 0 (worst) to 48 (best, no limitations), higher score indicates a better outcome. A negative change from baseline indicates worsening of disability. |
| Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5 | Baseline, Year 5 | The NIS+7 provides additional, objective measures of nerve fiber function and autonomic nerve function in participants with diabetic neuropathy. The NIS+7 includes the full NIS (NIS-W, NIS-R, NIS-S), sum of 5 nerve conduction studies (NCS) (Sural SNAP, tibial motor nerve distal latency, peroneal CMAP, motor nerve conduction velocity, motor nerve distal latency), vibration detection threshold, and pulse rate response to deep breathing. NIS-W is a measure of motor strength, comprised of cranial nerve and both upper and lower limb motor assessments. The score ranges from 0 to 192. A higher score indicates greater severity of disease. |
| Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5 | Baseline, Year 5 | 10-MWT is a measure of ambulatory ability and walk speed. It measures the speed (in meters per second \[m/s\]) of a participant to walk 10 meters. A negative change from baseline represents decreased ambulatory ability. |
| Change From Baseline in the Hand Grip Strength at Week 52 | Baseline, Week 52 | Hand grip strength was measured by dynamometer. Grip strength in the dominant arm is a measure of motor function, with a higher grip strength indicating better motor function. The mean change from baseline in the hand grip strength was reported. |
| Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage | Baseline, Year 5 | PND measures changes in the ambulatory ability including the need of walking aids on the following stages: 0 (no symptoms), I (sensory disturbances but preserved walking capability), II (impaired walking capability but ability to walk without a stick or crutches), IIIA (walking with help of 1 stick/crutch), IIIB (with help of 2 sticks/crutches), and IV (confined to wheelchair or bedridden). Lower scores indicate greater ambulatory function. The number of participants with change in the stage from baseline was reported as: Improved or worsened. |
| Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage | Baseline, Year 5 | FAP measures changes in the ambulatory ability including the need of walking aids on the following stages: 0 (no symptoms), I (unimpaired ambulation; mostly mild sensory, motor, and autonomic neuropathy in the lower limbs), II (assistance with ambulation required; moderate impairment of the lower limbs, upper limbs, and trunk), and III (wheelchair-bound or bedridden; severe sensory, motor, and autonomic involvement of all limbs). Lower scores indicate greater ambulatory function. The number of participants with change in the stage from baseline was reported as: Improved or worsened. |
| Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5 | Baseline, Year 5 | The NIS assessment is a 244-point composite measure of neurologic impairment which includes a physical exam of lower limbs, upper limbs, and cranial nerves to assess the components: motor strength/weakness (NIS-W), reflexes (NIS-R), and sensation (NIS-S). NIS total score is obtained by combining all the component scores, ranging from 0 to 244. Higher scores represent a greater severity of disease. A positive change from baseline indicates the worsening of neuropathy. |
| Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Baseline, Year 5 | IENFD (fibers/millimeter \[mm\]) is a measure for the pathologic evaluation of sensory and autonomic innervation. It is obtained by tandem 3 mm skin punch biopsies: one set of biopsies taken from the distal thigh and one set from the distal lower leg. An increase in nerve fiber density suggests improvement, while a decrease in nerve fiber density suggests worsening. |
| Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Baseline, Year 5 | SGNFD (meter/cubic millimeter \[m/mm\^3\]) is a measure for the pathologic evaluation of sensory and autonomic innervation. It is obtained by tandem 3 mm skin punch biopsies: one set of biopsies taken from the distal thigh and one set from the distal lower leg. An increase in nerve fiber density suggests improvement, while a decrease in nerve fiber density suggests worsening. |
| Change From Baseline in the Dermal Amyloid Burden at Year 5 | Baseline, Year 5 | Dermal Amyloid Burden is a measure for the pathologic evaluation of sensory and autonomic innervation and reported as % congo red stain. It is obtained by tandem 3 mm skin punch biopsies: one set of biopsies taken from the distal thigh and one set from the distal lower leg. |
| Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5 | Baseline, Year 5 | Manifestations of cardiac amyloid involvement were assessed through measurement of serum levels of the cardiac biomarker: troponin (micrograms per liter \[µg/L\]). The troponin I values \<0.1 μg/L were imputed to 0.1 thus the actual changes cannot be calculated for values \<0.1 μg/L. |
| Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5 | Baseline, Year 5 | Manifestations of cardiac amyloid involvement were assessed through measurement of serum levels of the cardiac biomarker: NT-proBNP (nanograms per liter \[ng/L\]). |
| Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5 | Baseline, Year 5 | The echocardiogram parameters analyzed included measures of systolic function: Average peak longitudinal strain (percentage \[%\]). |
| Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5 | Baseline, Year 5 | The echocardiogram parameters analyzed included measures of cardiac structure: LV relative wall thickness (ratio). |
| Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5 | Baseline, Year 5 | The echocardiogram parameters analyzed included measures of cardiac structure: LV mass (grams \[g\]). |
| Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5 | Baseline, Year 5 | The echocardiogram parameters analyzed included measures of diastolic function: LV end-diastolic volume (milliliters \[mL\]). |
| Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5 | Baseline, Year 5 | The echocardiogram parameters analyzed included measures of cardiac structure: Mean LV wall thickness (centimeters \[cm\]). |
| Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5 | Baseline, Year 5 | The echocardiogram parameters analyzed included measures of systolic function: Cardiac output (liters per minute \[L/min\]). |
| Percent Change From Baseline in Serum TTR Levels at Year 5 | Baseline, Year 5 | Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA). |
| Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification | Baseline, Year 5 | NYHA classification grades the severity of heart failure symptoms into the following stages: I (no symptoms; ordinary physical activity such as walking and climbing stairs does not cause fatigue or dyspnea), II (symptoms with ordinary physical activity; walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, in cold weather, in wind or when under emotional stress causes undue fatigue or dyspnea), III (symptoms with less than ordinary physical activity; walking 1 to 2 blocks on the level and climbing more than 1 flight of stairs in normal conditions causes undue fatigue or dyspnea), IV (symptoms at rest; inability to carry on any physical activity without fatigue or dyspnea). The number of participants with change in the stage from baseline was reported as: Improved or worsened. |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Cyprus, France, Germany, Italy, Japan, Malaysia, Mexico, Netherlands, Portugal, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at investigational sites in Asia, Europe, Canada, the United Kingdom, and the United States from 16 July 2015 to 23 November 2022.
Pre-assignment details
A total of 211 participants who completed either ALN-TTR02-003 (NCT01961921) or ALN-TTR02-004 (NCT01960348) studies were enrolled into the study to receive at least 1 dose of patisiran.
Participants by arm
| Arm | Count |
|---|---|
| Prior Placebo Group of Study 004 Participants who received placebo and completed parent study ALN-TTR02-004 (NCT01960348) were enrolled to receive 0.3 mg/kg patisiran IV Q3W up to 65.5 months. | 49 |
| Prior Patisiran Group of Study 004 Participants who received patisiran and completed parent study ALN-TTR02-004 (NCT01960348) were enrolled to receive 0.3 mg/kg patisiran IV Q3W up to 66.9 months. | 137 |
| Prior Patisiran Group of Study 003 Participants who received patisiran and completed parent study ALN-TTR02-003 (NCT01961921) were enrolled to receive 0.3 mg/kg patisiran IV Q3W up to 61.4 months. | 25 |
| Total | 211 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 8 | 0 |
| Overall Study | Death | 19 | 19 | 0 |
| Overall Study | Physician Decision | 1 | 5 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 10 | 3 |
Baseline characteristics
| Characteristic | Prior Placebo Group of Study 004 | Prior Patisiran Group of Study 004 | Prior Patisiran Group of Study 003 | Total |
|---|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 11.02 | 61.0 years STANDARD_DEVIATION 12.1 | 58.5 years STANDARD_DEVIATION 15.09 | 61.3 years STANDARD_DEVIATION 12.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 16 Participants | 2 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 121 Participants | 23 Participants | 183 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 14 Participants | 23 Participants | 0 Participants | 37 Participants |
| Race/Ethnicity, Customized Race Black/African or African American | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Missing | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race More than One Race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White/Caucasian | 34 Participants | 107 Participants | 25 Participants | 166 Participants |
| Serum Transthyretin (TTR) Level | 185.689 mg/L STANDARD_DEVIATION 56.2895 | 53.010 mg/L STANDARD_DEVIATION 43.1782 | 76.905 mg/L STANDARD_DEVIATION 47.9088 | 83.639 mg/L STANDARD_DEVIATION 70.5576 |
| Sex: Female, Male Female | 12 Participants | 35 Participants | 8 Participants | 55 Participants |
| Sex: Female, Male Male | 37 Participants | 102 Participants | 17 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 19 / 49 | 21 / 137 | 1 / 25 |
| other Total, other adverse events | 47 / 49 | 135 / 137 | 25 / 25 |
| serious Total, serious adverse events | 39 / 49 | 82 / 137 | 12 / 25 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs) Leading to Study Discontinuation
AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Time frame: First dose up to 28 days after last dose of study drug (approximately 5.6 years)
Population: Safety analysis set included all the enrolled participants who received at least 1 dose of patisiran in this study. Percentages are rounded off to the nearest decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prior Placebo Group of Study 004 | Percentage of Participants With Adverse Events (AEs) Leading to Study Discontinuation | 49.0 percentage of participants |
| Prior Patisiran Group of Study 004 | Percentage of Participants With Adverse Events (AEs) Leading to Study Discontinuation | 16.8 percentage of participants |
| Prior Patisiran Group of Study 003 | Percentage of Participants With Adverse Events (AEs) Leading to Study Discontinuation | 0.0 percentage of participants |
Secondary
Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5
10-MWT is a measure of ambulatory ability and walk speed. It measures the speed (in meters per second \[m/s\]) of a participant to walk 10 meters. A negative change from baseline represents decreased ambulatory ability.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5 | Baseline | 0.538 m/s | Standard Error 0.0553 |
| Prior Placebo Group of Study 004 | Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5 | Change From Baseline at Year 5 | 0.011 m/s | Standard Error 0.0339 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5 | Baseline | 0.851 m/s | Standard Error 0.0422 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5 | Change From Baseline at Year 5 | -0.050 m/s | Standard Error 0.0542 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5 | Baseline | 1.262 m/s | Standard Error 0.0826 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5 | Change From Baseline at Year 5 | -0.121 m/s | Standard Error 0.0487 |
Secondary
Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5
Manifestations of cardiac amyloid involvement were assessed through measurement of serum levels of the cardiac biomarker: NT-proBNP (nanograms per liter \[ng/L\]).
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5 | Baseline | 1957.649 ng/L | Standard Deviation 2731.3296 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5 | Change From Baseline at Year 5 | -18.490 ng/L | Standard Deviation 910.2156 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5 | Baseline | 1017.217 ng/L | Standard Deviation 1558.7632 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5 | Change From Baseline at Year 5 | 209.126 ng/L | Standard Deviation 487.214 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5 | Baseline | 281.899 ng/L | Standard Deviation 421.9627 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Cardiac Biomarker: N-terminal Prohormone of B-type Natriuretic Peptide (NT-proBNP) at Year 5 | Change From Baseline at Year 5 | 78.146 ng/L | Standard Deviation 266.1912 |
Secondary
Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5
Manifestations of cardiac amyloid involvement were assessed through measurement of serum levels of the cardiac biomarker: troponin (micrograms per liter \[µg/L\]). The troponin I values \<0.1 μg/L were imputed to 0.1 thus the actual changes cannot be calculated for values \<0.1 μg/L.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5 | Baseline | 0.109 µg/L | Standard Deviation 0.036 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5 | Change From Baseline at Year 5 | 0.546 µg/L | Standard Deviation 2.3345 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5 | Baseline | 0.112 µg/L | Standard Deviation 0.0963 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5 | Change From Baseline at Year 5 | -0.005 µg/L | Standard Deviation 0.0244 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5 | Baseline | 0.088 µg/L | Standard Deviation 0.0263 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5 | Change From Baseline at Year 5 | 0.014 µg/L | Standard Deviation 0.0277 |
Secondary
Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52
COMPASS 31 questionnaire measures autonomic symptoms in participants with neuropathy. The questionnaire consists of 31 clinically selected questions evaluating 6 autonomic domains (orthostatic intolerance, secretomotor, gastrointestinal, bladder, and pupillomotor). COMPASS 31 is measured on a scale from 0 to 100, with 100 representing maximum impairment.
Time frame: Baseline, Week 52
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52 | Baseline | 33.92 score on a scale | Standard Deviation 18.185 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52 | Change From Baseline at Week 52 | -3.70 score on a scale | Standard Deviation 12.957 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52 | Baseline | 25.37 score on a scale | Standard Deviation 17.01 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52 | Change From Baseline at Week 52 | 0.37 score on a scale | Standard Deviation 12.041 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52 | Baseline | 15.93 score on a scale | Standard Deviation 15.116 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Composite Autonomic Symptom Score (COMPASS 31) Total Score at Week 52 | Change From Baseline at Week 52 | -1.24 score on a scale | Standard Deviation 7.975 |
Secondary
Change From Baseline in the Dermal Amyloid Burden at Year 5
Dermal Amyloid Burden is a measure for the pathologic evaluation of sensory and autonomic innervation and reported as % congo red stain. It is obtained by tandem 3 mm skin punch biopsies: one set of biopsies taken from the distal thigh and one set from the distal lower leg.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis of the specified parameter at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Thigh: Baseline | 8.163 percent congo red stain | Standard Deviation 10.6544 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Thigh: Change From Baseline at Year 5 | -3.775 percent congo red stain | Standard Deviation 5.3387 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Leg: Baseline | 11.062 percent congo red stain | Standard Deviation 10.4857 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Leg: Change From Baseline at Year 5 | -7.475 percent congo red stain | Standard Deviation 5.6922 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Leg: Change From Baseline at Year 5 | -2.793 percent congo red stain | Standard Deviation 6.2309 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Thigh: Baseline | 8.205 percent congo red stain | Standard Deviation 10.8725 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Leg: Baseline | 10.386 percent congo red stain | Standard Deviation 12.3967 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Thigh: Change From Baseline at Year 5 | -1.103 percent congo red stain | Standard Deviation 7.5569 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Leg: Change From Baseline at Year 5 | -3.935 percent congo red stain | Standard Deviation 6.6372 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Thigh: Change From Baseline at Year 5 | -3.100 percent congo red stain | Standard Deviation 5.7269 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Leg: Baseline | 7.441 percent congo red stain | Standard Deviation 8.5566 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Dermal Amyloid Burden at Year 5 | Amyloid Stain, Thigh: Baseline | 5.908 percent congo red stain | Standard Deviation 7.6646 |
Secondary
Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5
The echocardiogram parameters analyzed included measures of systolic function: Average peak longitudinal strain (percentage \[%\]).
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5 | Baseline | -15.63 percentage | Standard Deviation 3.348 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5 | Change From Baseline at Year 5 | 3.43 percentage | Standard Deviation 3.634 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5 | Baseline | -15.96 percentage | Standard Deviation 3.283 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5 | Change From Baseline at Year 5 | 2.30 percentage | Standard Deviation 3.3 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5 | Baseline | -17.72 percentage | Standard Deviation 4.079 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5 | Change From Baseline at Year 5 | 1.62 percentage | Standard Deviation 3.082 |
Secondary
Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5
The echocardiogram parameters analyzed included measures of systolic function: Cardiac output (liters per minute \[L/min\]).
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5 | Baseline | 3.547 L/min | Standard Deviation 1.0373 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5 | Change From Baseline at Year 5 | -0.010 L/min | Standard Deviation 1.1551 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5 | Baseline | 3.840 L/min | Standard Deviation 1.1748 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5 | Change From Baseline at Year 5 | -0.283 L/min | Standard Deviation 1.1012 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5 | Baseline | 4.873 L/min | Standard Deviation 1.6902 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5 | Change From Baseline at Year 5 | -0.594 L/min | Standard Deviation 1.5476 |
Secondary
Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5
The echocardiogram parameters analyzed included measures of cardiac structure: LV mass (grams \[g\]).
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5 | Baseline | 238.166 grams | Standard Deviation 74.0536 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5 | Change From Baseline at Year 5 | 2.723 grams | Standard Deviation 52.1737 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5 | Baseline | 236.604 grams | Standard Deviation 85.8152 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5 | Change From Baseline at Year 5 | -4.222 grams | Standard Deviation 48.2397 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5 | Baseline | 198.570 grams | Standard Deviation 89.178 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5 | Change From Baseline at Year 5 | -17.152 grams | Standard Deviation 50.9296 |
Secondary
Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5
The echocardiogram parameters analyzed included measures of diastolic function: LV end-diastolic volume (milliliters \[mL\]).
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5 | Baseline | 80.591 mL | Standard Deviation 26.5862 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5 | Change From Baseline at Year 5 | 7.173 mL | Standard Deviation 15.9316 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5 | Baseline | 83.616 mL | Standard Deviation 25.699 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5 | Change From Baseline at Year 5 | -1.279 mL | Standard Deviation 20.0305 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5 | Baseline | 107.818 mL | Standard Deviation 34.8418 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5 | Change From Baseline at Year 5 | -11.710 mL | Standard Deviation 32.1329 |
Secondary
Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5
The echocardiogram parameters analyzed included measures of cardiac structure: LV relative wall thickness (ratio).
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5 | Baseline | 0.780 ratio | Standard Deviation 0.1616 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5 | Change From Baseline at Year 5 | -0.066 ratio | Standard Deviation 0.1344 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5 | Baseline | 0.717 ratio | Standard Deviation 0.184 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5 | Change From Baseline at Year 5 | -0.061 ratio | Standard Deviation 0.132 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5 | Baseline | 0.593 ratio | Standard Deviation 0.1802 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5 | Change From Baseline at Year 5 | -0.037 ratio | Standard Deviation 0.0887 |
Secondary
Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5
The echocardiogram parameters analyzed included measures of cardiac structure: Mean LV wall thickness (centimeters \[cm\]).
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5 | Baseline | 1.538 cm | Standard Deviation 0.2776 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5 | Change From Baseline at Year 5 | -0.035 cm | Standard Deviation 0.1782 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5 | Baseline | 1.463 cm | Standard Deviation 0.321 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5 | Change From Baseline at Year 5 | -0.041 cm | Standard Deviation 0.1874 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5 | Baseline | 1.249 cm | Standard Deviation 0.3321 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5 | Change From Baseline at Year 5 | -0.042 cm | Standard Deviation 0.1794 |
Secondary
Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5
The EQ-5D-5L is a patient-reported measure of QoL based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The overall score is rated on a scale from 0 (worst) to 1 (no impairment). Higher scores indicate a higher QoL. A negative change from baseline indicates worsening of QoL.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5 | Baseline | 0.4614 score on a scale | Standard Error 0.03347 |
| Prior Placebo Group of Study 004 | Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5 | Change From Baseline at Year 5 | 0.0361 score on a scale | Standard Error 0.04017 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5 | Baseline | 0.6444 score on a scale | Standard Error 0.01856 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5 | Change From Baseline at Year 5 | -0.0548 score on a scale | Standard Error 0.01767 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5 | Baseline | 0.7663 score on a scale | Standard Error 0.03336 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the EuroQOL-5 Dimensions-5 Levels (EQ-5D-5L) Index Score at Year 5 | Change From Baseline at Year 5 | -0.0166 score on a scale | Standard Error 0.02363 |
Secondary
Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5
EQ-VAS measures the participant's self-rated health on a vertical scale evaluated on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Higher scores indicate a higher QOL. A negative change from baseline indicates worsening of QoL.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5 | Baseline | 46.0 score on a scale | Standard Error 2.86 |
| Prior Placebo Group of Study 004 | Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5 | Change From Baseline at Year 5 | 9.3 score on a scale | Standard Error 5.03 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5 | Baseline | 57.8 score on a scale | Standard Error 1.82 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5 | Change From Baseline at Year 5 | -1.5 score on a scale | Standard Error 1.43 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5 | Baseline | 69.1 score on a scale | Standard Error 4.2 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the EuroQoL Visual Analogue Scale (EQ-VAS) Score at Year 5 | Change From Baseline at Year 5 | 1.5 score on a scale | Standard Error 2.99 |
Secondary
Change From Baseline in the Hand Grip Strength at Week 52
Hand grip strength was measured by dynamometer. Grip strength in the dominant arm is a measure of motor function, with a higher grip strength indicating better motor function. The mean change from baseline in the hand grip strength was reported.
Time frame: Baseline, Week 52
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Hand Grip Strength at Week 52 | Baseline | 10.23 kg | Standard Error 1.293 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Hand Grip Strength at Week 52 | Change From Baseline at Week 52 | 0.14 kg | Standard Error 0.461 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Hand Grip Strength at Week 52 | Change From Baseline at Week 52 | -0.34 kg | Standard Error 0.615 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Hand Grip Strength at Week 52 | Baseline | 18.03 kg | Standard Error 1.081 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Hand Grip Strength at Week 52 | Baseline | 27.86 kg | Standard Error 2.626 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Hand Grip Strength at Week 52 | Change From Baseline at Week 52 | -0.28 kg | Standard Error 0.807 |
Secondary
Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5
IENFD (fibers/millimeter \[mm\]) is a measure for the pathologic evaluation of sensory and autonomic innervation. It is obtained by tandem 3 mm skin punch biopsies: one set of biopsies taken from the distal thigh and one set from the distal lower leg. An increase in nerve fiber density suggests improvement, while a decrease in nerve fiber density suggests worsening.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis of the specified parameter at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Thigh: Baseline | 4.71 fibers/mm | Standard Deviation 5.249 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve, Fibers, Thigh: Change From Baseline at Year 5 | 0.28 fibers/mm | Standard Deviation 2.298 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Leg: Baseline | 0.47 fibers/mm | Standard Deviation 0.843 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Leg: Change From Baseline at Year 5 | -0.25 fibers/mm | Standard Deviation 0.495 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Leg: Change From Baseline at Year 5 | -1.31 fibers/mm | Standard Deviation 1.879 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Thigh: Baseline | 5.41 fibers/mm | Standard Deviation 5.291 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Leg: Baseline | 1.70 fibers/mm | Standard Deviation 3.183 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve, Fibers, Thigh: Change From Baseline at Year 5 | -2.75 fibers/mm | Standard Deviation 3.126 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Leg: Change From Baseline at Year 5 | -3.50 fibers/mm | Standard Deviation 8.428 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve, Fibers, Thigh: Change From Baseline at Year 5 | -5.53 fibers/mm | Standard Deviation 7.998 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Leg: Baseline | 3.66 fibers/mm | Standard Deviation 8.286 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Intraepidermal Nerve Fiber Density (IENFD) at Year 5 | Epidermal Nerve Fibers, Thigh: Baseline | 8.99 fibers/mm | Standard Deviation 10.027 |
Secondary
Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5
Nutritional status of participants was evaluated using the mBMI, calculated as BMI (kilograms per square meter \[kg/m\^2\]) multiplied by the concentration of serum albumin (grams per liter \[g/L\]). A positive change from baseline indicates improvement in nutritional status.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5 | Baseline | 881.8 kg.g/m^2.L | Standard Deviation 219.1 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5 | Change From Baseline at Year 5 | 74.0 kg.g/m^2.L | Standard Deviation 146.85 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5 | Baseline | 970.7 kg.g/m^2.L | Standard Deviation 218.4 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5 | Change From Baseline at Year 5 | 31.6 kg.g/m^2.L | Standard Deviation 119.28 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5 | Baseline | 1002.3 kg.g/m^2.L | Standard Deviation 173.8 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5 | Change From Baseline at Year 5 | 77.8 kg.g/m^2.L | Standard Deviation 91.36 |
Secondary
Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5
The NIS+7 provides additional, objective measures of nerve fiber function and autonomic nerve function in participants with diabetic neuropathy. The NIS+7 includes the full NIS (NIS-W, NIS-R, NIS-S), sum of 5 nerve conduction studies (NCS) (Sural SNAP, tibial motor nerve distal latency, peroneal CMAP, motor nerve conduction velocity, motor nerve distal latency), vibration detection threshold, and pulse rate response to deep breathing. NIS-W is a measure of motor strength, comprised of cranial nerve and both upper and lower limb motor assessments. The score ranges from 0 to 192. A higher score indicates greater severity of disease.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5 | Baseline | 47.01 score on a scale | Standard Deviation 31.323 |
| Prior Placebo Group of Study 004 | Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5 | Change From Baseline at Year 5 | 9.10 score on a scale | Standard Deviation 13.297 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5 | Baseline | 33.26 score on a scale | Standard Deviation 27.434 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5 | Change From Baseline at Year 5 | 7.37 score on a scale | Standard Deviation 11.707 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5 | Baseline | 15.02 score on a scale | Standard Deviation 17.988 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the NIS+7 Component: NIS-Weakness (NIS-W) Score at Year 5 | Change From Baseline at Year 5 | 6.97 score on a scale | Standard Deviation 13.235 |
Secondary
Change From Baseline in the NIS+7 Total Score at Week 52
The NIS+7 provides additional, objective measures of nerve fibre function and autonomic nerve function in participants with diabetic neuropathy. The NIS+7 includes the full NIS, sum of 5 nerve conduction studies (NCS) (Sural sensory nerve action potential \[SNAP\], tibial motor nerve distal latency, peroneal compound motor action potential \[CMAP\], motor nerve conduction velocity, motor nerve distal latency), vibration detection threshold, and pulse rate response to deep breathing. The total NIS+7 score is obtained by combining all the component scores, ranging from 0 (no impairment) to 270 points (maximum impairment). A positive change from baseline indicates worsening.
Time frame: Baseline, Week 52
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the NIS+7 Total Score at Week 52 | Baseline | 98.42 score on a scale | Standard Error 42.281 |
| Prior Placebo Group of Study 004 | Change From Baseline in the NIS+7 Total Score at Week 52 | Change From Baseline at Week 52 | 1.44 score on a scale | Standard Error 2.061 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the NIS+7 Total Score at Week 52 | Baseline | 78.74 score on a scale | Standard Error 39.417 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the NIS+7 Total Score at Week 52 | Change From Baseline at Week 52 | 1.49 score on a scale | Standard Error 0.894 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the NIS+7 Total Score at Week 52 | Baseline | 49.66 score on a scale | Standard Error 31.319 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the NIS+7 Total Score at Week 52 | Change From Baseline at Week 52 | 3.23 score on a scale | Standard Error 2.616 |
Secondary
Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5
The Norfolk QoL-DN questionnaire is a standardized 47-item patient-reported outcomes measure, sensitive to the perception of the effects of diabetic neuropathy by the participant. The scores range from -4 (best possible QOL) to 136 (worst possible QOL). A negative change from baseline represents improved QOL.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5 | Baseline | 72.7 score on a scale | Standard Deviation 28.1 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5 | Change From Baseline at Year 5 | 3.3 score on a scale | Standard Deviation 13.91 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5 | Baseline | 54.5 score on a scale | Standard Deviation 30.87 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5 | Change From Baseline at Year 5 | 4.5 score on a scale | Standard Deviation 17.19 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5 | Baseline | 34.0 score on a scale | — |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Total Score at Year 5 | Change From Baseline at Year 5 | -18.0 score on a scale | — |
Secondary
Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5
The R-ODS is a 24-item patient-reported questionnaire that specifically captures activity and social participation limitations. It measures the level of disability on a scale of 0 (worst) to 48 (best, no limitations), higher score indicates a better outcome. A negative change from baseline indicates worsening of disability.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5 | Baseline | 20.3 score on a scale | Standard Deviation 12.74 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5 | Change From Baseline at Year 5 | -2.9 score on a scale | Standard Deviation 5.25 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5 | Baseline | 29.7 score on a scale | Standard Deviation 12.56 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5 | Change From Baseline at Year 5 | -4.1 score on a scale | Standard Deviation 6.78 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5 | Baseline | 36.7 score on a scale | Standard Deviation 10.29 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Rasch-built Overall Disability Scale (R-ODS) at Year 5 | Change From Baseline at Year 5 | -2.7 score on a scale | Standard Deviation 3.6 |
Secondary
Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5
SGNFD (meter/cubic millimeter \[m/mm\^3\]) is a measure for the pathologic evaluation of sensory and autonomic innervation. It is obtained by tandem 3 mm skin punch biopsies: one set of biopsies taken from the distal thigh and one set from the distal lower leg. An increase in nerve fiber density suggests improvement, while a decrease in nerve fiber density suggests worsening.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number of participants analyzed' indicates the number of participants with data available for analysis of the specified parameter at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Thigh: Baseline | 10.82 m/mm^3 | Standard Deviation 6.638 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Thigh: Change From Baseline at Year 5 | -0.56 m/mm^3 | Standard Deviation 2.648 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Leg: Baseline | 2.82 m/mm^3 | Standard Deviation 3.363 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Leg: Change From Baseline at Year 5 | 1.43 m/mm^3 | Standard Deviation 2.351 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Leg: Change From Baseline at Year 5 | -2.47 m/mm^3 | Standard Deviation 3.605 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Thigh: Baseline | 9.67 m/mm^3 | Standard Deviation 4.942 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Leg: Baseline | 4.99 m/mm^3 | Standard Deviation 4.274 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Thigh: Change From Baseline at Year 5 | -2.49 m/mm^3 | Standard Deviation 5.636 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Leg: Change From Baseline at Year 5 | -1.31 m/mm^3 | Standard Deviation 2.867 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Thigh: Change From Baseline at Year 5 | -3.29 m/mm^3 | Standard Deviation 4.323 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Leg: Baseline | 5.93 m/mm^3 | Standard Deviation 4.355 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Sweat Gland Nerve Fiber Density (SGNFD) at Year 5 | Sweat Gland Nerve Fibers, Thigh: Baseline | 9.14 m/mm^3 | Standard Deviation 4.802 |
Secondary
Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3
The mNIS+7 is a composite measure of neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs, and cranial nerves to assess motor strength/weakness (192 points), reflexes (20 points), electrophysiologic measurement of small and large nerve fiber function (10 points), sensory testing (80 points), and postural blood pressure (2 points). The total mNIS+7 composite score is obtained by combining all the component scores, ranging from 0 (no impairment) to 304 (maximum impairment). A negative change from baseline indicates an improvement in neuropathy.
Time frame: Baseline, Year 3
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3 | Baseline | 101.07 score on a scale | Standard Error 43.774 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3 | Change From Baseline at Year 3 | -6.69 score on a scale | Standard Error 3.389 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3 | Baseline | 74.72 score on a scale | Standard Error 42.584 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3 | Change From Baseline at Year 3 | 8.07 score on a scale | Standard Error 1.874 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3 | Baseline | 45.66 score on a scale | Standard Error 31.64 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Total Modified NIS (mNIS +7) Composite Score At Year 3 | Change From Baseline at Year 3 | 5.46 score on a scale | Standard Error 2.45 |
Secondary
Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5
The NIS assessment is a 244-point composite measure of neurologic impairment which includes a physical exam of lower limbs, upper limbs, and cranial nerves to assess the components: motor strength/weakness (NIS-W), reflexes (NIS-R), and sensation (NIS-S). NIS total score is obtained by combining all the component scores, ranging from 0 to 244. Higher scores represent a greater severity of disease. A positive change from baseline indicates the worsening of neuropathy.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Placebo Group of Study 004 | Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5 | Change From Baseline at Year 5 | 11.45 score on a scale | Standard Deviation 16.566 |
| Prior Placebo Group of Study 004 | Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5 | Baseline | 81.47 score on a scale | Standard Deviation 41.674 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5 | Baseline | 62.26 score on a scale | Standard Deviation 37.875 |
| Prior Patisiran Group of Study 004 | Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5 | Change From Baseline at Year 5 | 10.72 score on a scale | Standard Deviation 13.654 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5 | Baseline | 35.48 score on a scale | Standard Deviation 28.686 |
| Prior Patisiran Group of Study 003 | Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5 | Change From Baseline at Year 5 | 11.18 score on a scale | Standard Deviation 17.554 |
Secondary
Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage
FAP measures changes in the ambulatory ability including the need of walking aids on the following stages: 0 (no symptoms), I (unimpaired ambulation; mostly mild sensory, motor, and autonomic neuropathy in the lower limbs), II (assistance with ambulation required; moderate impairment of the lower limbs, upper limbs, and trunk), and III (wheelchair-bound or bedridden; severe sensory, motor, and autonomic involvement of all limbs). Lower scores indicate greater ambulatory function. The number of participants with change in the stage from baseline was reported as: Improved or worsened.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Placebo Group of Study 004 | Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage | Improved | 0 Participants |
| Prior Placebo Group of Study 004 | Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage | Worsened | 5 Participants |
| Prior Patisiran Group of Study 004 | Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage | Improved | 3 Participants |
| Prior Patisiran Group of Study 004 | Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage | Worsened | 13 Participants |
| Prior Patisiran Group of Study 003 | Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage | Improved | 1 Participants |
| Prior Patisiran Group of Study 003 | Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage | Worsened | 2 Participants |
Secondary
Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification
NYHA classification grades the severity of heart failure symptoms into the following stages: I (no symptoms; ordinary physical activity such as walking and climbing stairs does not cause fatigue or dyspnea), II (symptoms with ordinary physical activity; walking or climbing stairs rapidly, walking uphill, walking or stair climbing after meals, in cold weather, in wind or when under emotional stress causes undue fatigue or dyspnea), III (symptoms with less than ordinary physical activity; walking 1 to 2 blocks on the level and climbing more than 1 flight of stairs in normal conditions causes undue fatigue or dyspnea), IV (symptoms at rest; inability to carry on any physical activity without fatigue or dyspnea). The number of participants with change in the stage from baseline was reported as: Improved or worsened.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Placebo Group of Study 004 | Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification | Improved | 2 Participants |
| Prior Placebo Group of Study 004 | Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification | Worsened | 4 Participants |
| Prior Patisiran Group of Study 004 | Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification | Improved | 13 Participants |
| Prior Patisiran Group of Study 004 | Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification | Worsened | 18 Participants |
| Prior Patisiran Group of Study 003 | Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification | Improved | 1 Participants |
| Prior Patisiran Group of Study 003 | Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification | Worsened | 4 Participants |
Secondary
Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage
PND measures changes in the ambulatory ability including the need of walking aids on the following stages: 0 (no symptoms), I (sensory disturbances but preserved walking capability), II (impaired walking capability but ability to walk without a stick or crutches), IIIA (walking with help of 1 stick/crutch), IIIB (with help of 2 sticks/crutches), and IV (confined to wheelchair or bedridden). Lower scores indicate greater ambulatory function. The number of participants with change in the stage from baseline was reported as: Improved or worsened.
Time frame: Baseline, Year 5
Population: Full analysis set included all participants who were enrolled in this study. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Placebo Group of Study 004 | Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage | Improved | 1 Participants |
| Prior Placebo Group of Study 004 | Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage | Worsened | 8 Participants |
| Prior Patisiran Group of Study 004 | Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage | Improved | 9 Participants |
| Prior Patisiran Group of Study 004 | Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage | Worsened | 35 Participants |
| Prior Patisiran Group of Study 003 | Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage | Improved | 3 Participants |
| Prior Patisiran Group of Study 003 | Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage | Worsened | 5 Participants |
Secondary
Percent Change From Baseline in Serum TTR Levels at Year 5
Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA).
Time frame: Baseline, Year 5
Population: PD analysis set included all participants who received at least 1 dose of patisiran in this study and have had both baseline and at least 1 post-baseline PD assessment (either TTR or vitamin A). 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prior Placebo Group of Study 004 | Percent Change From Baseline in Serum TTR Levels at Year 5 | -90.010 percent change | Standard Deviation 7.4802 |
| Prior Patisiran Group of Study 004 | Percent Change From Baseline in Serum TTR Levels at Year 5 | -37.660 percent change | Standard Deviation 35.2948 |
| Prior Patisiran Group of Study 003 | Percent Change From Baseline in Serum TTR Levels at Year 5 | -39.965 percent change | Standard Deviation 56.5274 |