Trial Outcomes & Findings for The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Participants Who Have Already Been Treated With ALN-TTR02 (Patisiran) (NCT NCT02510261)

Last Updated: 2023-12-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

211 participants

Primary outcome timeframe

First dose up to 28 days after last dose of study drug (approximately 5.6 years)

Results posted on

2023-12-06

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Prior Placebo Group of Study 004 Participants who received placebo and completed parent study ALN-TTR02-004 (NCT01960348) were enrolled to receive 0.3 milligrams per kilogram (mg/kg) patisiran intravenously (IV) once every 3 weeks (Q3W) up to 65.5 months.	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.	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.
Overall Study STARTED	49	137	25
Overall Study Full Analysis Set	49	137	25
Overall Study Safety Analysis Set	49	137	25
Overall Study Pharmacodynamic (PD) Analysis Set	40	128	24
Overall Study COMPLETED	21	95	22
Overall Study NOT COMPLETED	28	42	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Prior Placebo Group of Study 004 Participants who received placebo and completed parent study ALN-TTR02-004 (NCT01960348) were enrolled to receive 0.3 milligrams per kilogram (mg/kg) patisiran intravenously (IV) once every 3 weeks (Q3W) up to 65.5 months.	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.	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.
Overall Study Adverse Event	5	8	0
Overall Study Physician Decision	1	5	0
Overall Study Death	19	19	0
Overall Study Withdrawal by Subject	3	10	3

Baseline Characteristics

'Number analyzed' indicates the number of participants with data available for analysis of the specified measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.	Total n=211 Participants Total of all reporting groups
Age, Continuous	63.5 years STANDARD_DEVIATION 11.02 • n=49 Participants	61.0 years STANDARD_DEVIATION 12.10 • n=137 Participants	58.5 years STANDARD_DEVIATION 15.09 • n=25 Participants	61.3 years STANDARD_DEVIATION 12.28 • n=211 Participants
Sex: Female, Male Female	12 Participants n=49 Participants	35 Participants n=137 Participants	8 Participants n=25 Participants	55 Participants n=211 Participants
Sex: Female, Male Male	37 Participants n=49 Participants	102 Participants n=137 Participants	17 Participants n=25 Participants	156 Participants n=211 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=49 Participants	16 Participants n=137 Participants	2 Participants n=25 Participants	27 Participants n=211 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=49 Participants	121 Participants n=137 Participants	23 Participants n=25 Participants	183 Participants n=211 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=49 Participants	0 Participants n=137 Participants	0 Participants n=25 Participants	1 Participants n=211 Participants
Race/Ethnicity, Customized Race · Asian	14 Participants n=49 Participants	23 Participants n=137 Participants	0 Participants n=25 Participants	37 Participants n=211 Participants
Race/Ethnicity, Customized Race · Black/African or African American	0 Participants n=49 Participants	4 Participants n=137 Participants	0 Participants n=25 Participants	4 Participants n=211 Participants
Race/Ethnicity, Customized Race · White/Caucasian	34 Participants n=49 Participants	107 Participants n=137 Participants	25 Participants n=25 Participants	166 Participants n=211 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=49 Participants	2 Participants n=137 Participants	0 Participants n=25 Participants	2 Participants n=211 Participants
Race/Ethnicity, Customized Race · More than One Race	0 Participants n=49 Participants	1 Participants n=137 Participants	0 Participants n=25 Participants	1 Participants n=211 Participants
Race/Ethnicity, Customized Race · Missing	1 Participants n=49 Participants	0 Participants n=137 Participants	0 Participants n=25 Participants	1 Participants n=211 Participants
Serum Transthyretin (TTR) Level	185.689 mg/L STANDARD_DEVIATION 56.2895 • n=40 Participants • 'Number analyzed' indicates the number of participants with data available for analysis of the specified measure.	53.010 mg/L STANDARD_DEVIATION 43.1782 • n=128 Participants • 'Number analyzed' indicates the number of participants with data available for analysis of the specified measure.	76.905 mg/L STANDARD_DEVIATION 47.9088 • n=24 Participants • 'Number analyzed' indicates the number of participants with data available for analysis of the specified measure.	83.639 mg/L STANDARD_DEVIATION 70.5576 • n=192 Participants • 'Number analyzed' indicates the number of participants with data available for analysis of the specified measure.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Percentage of Participants With Adverse Events (AEs) Leading to Study Discontinuation	49.0 percentage of participants	16.8 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Total Neuropathy Impairment Score (NIS) at Year 5 Baseline	81.47 score on a scale Standard Deviation 41.674	62.26 score on a scale Standard Deviation 37.875	35.48 score on a scale Standard Deviation 28.686
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	10.72 score on a scale Standard Deviation 13.654	11.18 score on a scale Standard Deviation 17.554

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
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	74.72 score on a scale Standard Error 42.584	45.66 score on a scale Standard Error 31.640
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	8.07 score on a scale Standard Error 1.874	5.46 score on a scale Standard Error 2.450

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the NIS+7 Total Score at Week 52 Baseline	98.42 score on a scale Standard Error 42.281	78.74 score on a scale Standard Error 39.417	49.66 score on a scale Standard Error 31.319
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	1.49 score on a scale Standard Error 0.894	3.23 score on a scale Standard Error 2.616

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
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 28.10	54.5 score on a scale Standard Deviation 30.87	34.0 score on a scale Standard Deviation NA Standard deviation (SD) cannot be estimated for one participant.
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	4.5 score on a scale Standard Deviation 17.19	-18.0 score on a scale Standard Deviation NA Standard deviation (SD) cannot be estimated for one participant.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
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	0.6444 score on a scale Standard Error 0.01856	0.7663 score on a scale Standard Error 0.03336
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	-0.0548 score on a scale Standard Error 0.01767	-0.0166 score on a scale Standard Error 0.02363

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
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	57.8 score on a scale Standard Error 1.82	69.1 score on a scale Standard Error 4.20
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	-1.5 score on a scale Standard Error 1.43	1.5 score on a scale Standard Error 2.99

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
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	25.37 score on a scale Standard Deviation 17.010	15.93 score on a scale Standard Deviation 15.116
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	0.37 score on a scale Standard Deviation 12.041	-1.24 score on a scale Standard Deviation 7.975

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Modified Body Mass Index (mBMI) at Year 5 Baseline	881.8 kg.g/m^2.L Standard Deviation 219.10	970.7 kg.g/m^2.L Standard Deviation 218.40	1002.3 kg.g/m^2.L Standard Deviation 173.80
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	31.6 kg.g/m^2.L Standard Deviation 119.28	77.8 kg.g/m^2.L Standard Deviation 91.36

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
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	29.7 score on a scale Standard Deviation 12.56	36.7 score on a scale Standard Deviation 10.29
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	-4.1 score on a scale Standard Deviation 6.78	-2.7 score on a scale Standard Deviation 3.60

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
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	33.26 score on a scale Standard Deviation 27.434	15.02 score on a scale Standard Deviation 17.988
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	7.37 score on a scale Standard Deviation 11.707	6.97 score on a scale Standard Deviation 13.235

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the 10-meter Walk Test (10-MWT) Speed at Year 5 Baseline	0.538 m/s Standard Error 0.0553	0.851 m/s Standard Error 0.0422	1.262 m/s Standard Error 0.0826
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	-0.050 m/s Standard Error 0.0542	-0.121 m/s Standard Error 0.0487

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Hand Grip Strength at Week 52 Baseline	10.23 kg Standard Error 1.293	18.03 kg Standard Error 1.081	27.86 kg Standard Error 2.626
Change From Baseline in the Hand Grip Strength at Week 52 Change From Baseline at Week 52	0.14 kg Standard Error 0.461	-0.34 kg Standard Error 0.615	-0.28 kg Standard Error 0.807

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=21 Participants 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.	Prior Patisiran Group of Study 004 n=94 Participants 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.	Prior Patisiran Group of Study 003 n=22 Participants 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.
Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage Improved	1 Participants	9 Participants	3 Participants
Number of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Stage Worsened	8 Participants	35 Participants	5 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=21 Participants 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.	Prior Patisiran Group of Study 004 n=93 Participants 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.	Prior Patisiran Group of Study 003 n=22 Participants 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.
Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage Improved	0 Participants	3 Participants	1 Participants
Number of Participants With Change From Baseline in the Familial Amyloidotic Polyneuropathy (FAP) Stage Worsened	5 Participants	13 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=20 Participants 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.	Prior Patisiran Group of Study 004 n=87 Participants 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.	Prior Patisiran Group of Study 003 n=21 Participants 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.
Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification Improved	2 Participants	13 Participants	1 Participants
Number of Participants With Change From Baseline in the New York Heart Association (NYHA) Classification Worsened	4 Participants	18 Participants	4 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=15 Participants 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.	Prior Patisiran Group of Study 004 n=61 Participants 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.	Prior Patisiran Group of Study 003 n=19 Participants 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.
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	5.41 fibers/mm Standard Deviation 5.291	8.99 fibers/mm Standard Deviation 10.027
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	-2.75 fibers/mm Standard Deviation 3.126	-5.53 fibers/mm Standard Deviation 7.998
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	1.70 fibers/mm Standard Deviation 3.183	3.66 fibers/mm Standard Deviation 8.286
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	-1.31 fibers/mm Standard Deviation 1.879	-3.50 fibers/mm Standard Deviation 8.428

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=15 Participants 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.	Prior Patisiran Group of Study 004 n=59 Participants 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.	Prior Patisiran Group of Study 003 n=19 Participants 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.
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	9.67 m/mm^3 Standard Deviation 4.942	9.14 m/mm^3 Standard Deviation 4.802
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	-2.49 m/mm^3 Standard Deviation 5.636	-3.29 m/mm^3 Standard Deviation 4.323
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	4.99 m/mm^3 Standard Deviation 4.274	5.93 m/mm^3 Standard Deviation 4.355
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	-2.47 m/mm^3 Standard Deviation 3.605	-1.31 m/mm^3 Standard Deviation 2.867

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=15 Participants 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.	Prior Patisiran Group of Study 004 n=61 Participants 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.	Prior Patisiran Group of Study 003 n=18 Participants 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.
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	8.205 percent congo red stain Standard Deviation 10.8725	5.908 percent congo red stain Standard Deviation 7.6646
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	-1.103 percent congo red stain Standard Deviation 7.5569	-3.100 percent congo red stain Standard Deviation 5.7269
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	10.386 percent congo red stain Standard Deviation 12.3967	7.441 percent congo red stain Standard Deviation 8.5566
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	-2.793 percent congo red stain Standard Deviation 6.2309	-3.935 percent congo red stain Standard Deviation 6.6372

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Cardiac Biomarker: Serum Troponin I at Year 5 Baseline	0.109 µg/L Standard Deviation 0.0360	0.112 µg/L Standard Deviation 0.0963	0.088 µg/L Standard Deviation 0.0263
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	-0.005 µg/L Standard Deviation 0.0244	0.014 µg/L Standard Deviation 0.0277

SECONDARY outcome

Timeframe: Baseline, Year 5

Manifestations of cardiac amyloid involvement were assessed through measurement of serum levels of the cardiac biomarker: NT-proBNP (nanograms per liter \[ng/L\]).

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
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	1017.217 ng/L Standard Deviation 1558.7632	281.899 ng/L Standard Deviation 421.9627
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	209.126 ng/L Standard Deviation 487.2140	78.146 ng/L Standard Deviation 266.1912

SECONDARY outcome

Timeframe: Baseline, Year 5

The echocardiogram parameters analyzed included measures of systolic function: Average peak longitudinal strain (percentage \[%\]).

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=136 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Echocardiogram Parameter: Average Peak Longitudinal Strain at Year 5 Baseline	-15.63 percentage Standard Deviation 3.348	-15.96 percentage Standard Deviation 3.283	-17.72 percentage Standard Deviation 4.079
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	2.30 percentage Standard Deviation 3.300	1.62 percentage Standard Deviation 3.082

SECONDARY outcome

Timeframe: Baseline, Year 5

The echocardiogram parameters analyzed included measures of cardiac structure: LV mass (grams \[g\]).

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Echocardiogram Parameter: Left Ventricular (LV) Mass at Year 5 Baseline	238.166 grams Standard Deviation 74.0536	236.604 grams Standard Deviation 85.8152	198.570 grams Standard Deviation 89.1780
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	-4.222 grams Standard Deviation 48.2397	-17.152 grams Standard Deviation 50.9296

SECONDARY outcome

Timeframe: Baseline, Year 5

The echocardiogram parameters analyzed included measures of diastolic function: LV end-diastolic volume (milliliters \[mL\]).

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=136 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Echocardiogram Parameter: LV End-diastolic Volume at Year 5 Baseline	80.591 mL Standard Deviation 26.5862	83.616 mL Standard Deviation 25.6990	107.818 mL Standard Deviation 34.8418
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	-1.279 mL Standard Deviation 20.0305	-11.710 mL Standard Deviation 32.1329

SECONDARY outcome

Timeframe: Baseline, Year 5

The echocardiogram parameters analyzed included measures of cardiac structure: LV relative wall thickness (ratio).

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Echocardiogram Parameter: LV Relative Wall Thickness at Year 5 Baseline	0.780 ratio Standard Deviation 0.1616	0.717 ratio Standard Deviation 0.1840	0.593 ratio Standard Deviation 0.1802
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	-0.061 ratio Standard Deviation 0.1320	-0.037 ratio Standard Deviation 0.0887

SECONDARY outcome

Timeframe: Baseline, Year 5

The echocardiogram parameters analyzed included measures of cardiac structure: Mean LV wall thickness (centimeters \[cm\]).

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=137 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Echocardiogram Parameter: Mean LV Wall Thickness at Year 5 Baseline	1.538 cm Standard Deviation 0.2776	1.463 cm Standard Deviation 0.3210	1.249 cm Standard Deviation 0.3321
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	-0.041 cm Standard Deviation 0.1874	-0.042 cm Standard Deviation 0.1794

SECONDARY outcome

Timeframe: Baseline, Year 5

The echocardiogram parameters analyzed included measures of systolic function: Cardiac output (liters per minute \[L/min\]).

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=49 Participants 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.	Prior Patisiran Group of Study 004 n=136 Participants 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.	Prior Patisiran Group of Study 003 n=25 Participants 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.
Change From Baseline in the Echocardiogram Parameter: Cardiac Output at Year 5 Baseline	3.547 L/min Standard Deviation 1.0373	3.840 L/min Standard Deviation 1.1748	4.873 L/min Standard Deviation 1.6902
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	-0.283 L/min Standard Deviation 1.1012	-0.594 L/min Standard Deviation 1.5476

SECONDARY outcome

Timeframe: 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.

Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA).

Outcome measures

Outcome measures
Measure	Prior Placebo Group of Study 004 n=19 Participants 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.	Prior Patisiran Group of Study 004 n=80 Participants 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.	Prior Patisiran Group of Study 003 n=21 Participants 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.
Percent Change From Baseline in Serum TTR Levels at Year 5	-90.010 percent change Standard Deviation 7.4802	-37.660 percent change Standard Deviation 35.2948	-39.965 percent change Standard Deviation 56.5274

Adverse Events

Prior Placebo Group of Study 004

Serious events: 39 serious events

Other events: 47 other events

Deaths: 19 deaths

Prior Patisiran Group of Study 004

Serious events: 82 serious events

Other events: 135 other events

Deaths: 21 deaths

Prior Patisiran Group of Study 003

Serious events: 12 serious events

Other events: 25 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals Inc

Phone: 866-330-0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place