CompletedNCT01737398Updated Jul 17, 2019Results posted

Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy

A Phase 2/3 interventional study of Inotersen and Placebo in FAP, Familial Amyloid Polyneuropathy and TTR, sponsored by Ionis Pharmaceuticals, Inc.. Completed at 24 sites in 10 countries. Open to participants aged 18 Years to 82 Years. Per ClinicalTrials.gov, last updated 2019-07-17.

Sponsored by Ionis Pharmaceuticals, Inc. · Phase 2/3, Interventional, and Treatment

Phase: Phase 2/3
Study type: Interventional
Enrollment: 173
Allocation: Randomized
Ages: 18 Years to 82 Years
Sex: All

Study summary

The purpose of this study is to evaluate the efficacy and safety of inotersen given for 65 weeks in participants with Familial Amyloid Polyneuropathy (FAP).

Read the detailed description

FAP is a rare, hereditary disease caused by mutations in the transthyretin (TTR) protein. TTR is made by the liver and secreted into the blood. TTR mutations cause it to misfold and deposit in multiple organs causing FAP.

Inotersen (also known as ISIS 420915) is an antisense drug that was designed to decrease the amount of mutant and normal TTR made by the liver. It is predicted that decreasing the amount of TTR protein would result in a decrease in the formation of TTR deposits, and thus slow or stop disease progression.

The purpose of this study is to determine if inotersen can slow or stop the nerve damage caused by TTR deposits. This study will enroll late Stage 1 and early Stage 2 FAP participants. Participants will receive either inotersen or placebo for 65 weeks.

Conditions studied

FAP
Familial Amyloid Polyneuropathy
TTR
Transthyretin
Amyloidosis

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Keywords

FAP
Familial Amyloid Polyneuropathy
TTR
Transthyretin
Amyloidosis

In context

Polyneuropathies

256 studies on the registry are indexed under Polyneuropathies; 50 are open to participants now.

This study's enrollment of 173 is above the median of 75 across 162 interventional studies indexed under Polyneuropathies.

Browse Polyneuropathies studies →

Lead sponsor

Ionis Pharmaceuticals, Inc. is the lead sponsor of 116 studies on the registry; 10 are open to participants now.

Of its 48 completed or terminated interventional studies of FDA-regulated products, 21 (44%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 82 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Stage 1 and Stage 2 FAP participants with the following:
1. NIS score within protocol criteria
2. Documented transthyretin variant by genotyping
3. Documented amyloid deposit by biopsy
Females of child-bearing potential must use appropriate contraception and be non-pregnant and non-lactating. Males engaging in relations of child-bearing potential are to use appropriate contraception

Exclusion criteria

Exclusion Criteria:

Low Retinol level at screen
Karnofsky performance status ≤50
Poor Renal function
Known type 1 or type 2 diabetes mellitus
Other causes of sensorimotor or autonomic neuropathy (for example, autoimmune disease)
If previously treated with Vyndaqel®, will need to have discontinued treatment for 2 weeks prior to Study Day 1. If previously treated with Diflunisal, will need to have discontinued treatment for 3 days prior to Study Day 1
Previous treatment with any oligonucleotide or siRNA within 12 months of screening
Prior liver transplant or anticipated liver transplant within 1 year of screening
New York Heart Association (NYHA) functional classification of ≥3
Acute Coronary Syndrome or major surgery within 3 months of screening
Known Primary or Leptomeningeal Amyloidosis
Anticipated survival less than 2 years
Any other conditions in the opinion of the investigator which interfere with the participant participating in or completing the study

Study design

Phase: Phase 2 / Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 173 participants (actual)

Study arms

Active comparator
Inotersen
300 mg inotersen administered subcutaneously (SC) 3 times on alternate days in the first week and then once-weekly for 64 weeks
Drug: Inotersen
Active comparator
Placebo
Placebo administered SC 3 times on alternate days in the first week and then once-weekly for 64 weeks
Drug: Placebo

Interventions

DrugInotersen
Also known as: TEGSEDI, IONIS-TTR Rx, ISIS 420915
DrugPlacebo

What researchers measure

Primary outcomes

Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66
The mNIS+7 composite score is a measure of neurologic impairment that evaluates muscle weakness, sensation, reflexes, nerve conduction, and autonomic function. The mNIS+7 Composite Score has a range of -22.32 to 346.32 and a higher mNIS+7 composite score indicates lower function.
Time frame: Baseline and Week 66
Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66
The Norfolk QoL-DN score is a measure of physical function/large fiber neuropathy, symptoms, activities of daily living, small fiber neuropathy, and autonomic neuropathy. The Norfolk QoL-DN total score has a range of -4 to 136, and a higher Norfolk QoL-DN score indicates poorer QoL.
Time frame: Baseline and Week 66

Secondary outcomes

Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66
The Norfolk QoL-DN symptoms score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN symptoms domain score has a range of 0-32, and a higher Norfolk QoL-DN score indicates poorer QoL.
Time frame: Baseline and Week 66
Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66
The Norfolk QoL-DN physical functioning/large fiber neuropathy domain score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN physical function/large fiber neuropathy domain score has a range of -4 to 56, and a higher Norfolk QoL-DN domain score indicates poorer QoL.
Time frame: Baseline and Week 66
Change From Baseline In Modified Body Mass Index (mBMI) at Week 65
The mBMI is the BMI multiplied by the serum albumin g/L
Time frame: Baseline and Week 65
Change From Baseline In Body Mass Index (BMI) at Week 65
Time frame: Baseline and Week 65
Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66
The NIS score is a measure of neurologic impairment. The NIS Score has a range of 0 to 244 and a higher NIS score indicates lower function.
Time frame: Baseline and Week 66
Change From Baseline in Modified +7 at Week 66
The Modified +7 score is a version of the NIS score that is a measure of neurologic impairment. The Modified +7 Score has a range of -22.32 to 102.32 and a higher NIS score indicates lower function.
Time frame: Baseline and Week 66
Change From Baseline in NIS+7 at Week 66
The NIS+7 score is a version of the NIS score that is a measure of neurologic impairment. The NIS+7 Score has a range of -26.04 to 270.04 and a higher NIS score indicates lower function.
Time frame: Baseline and Week 66
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set
GLS by ECHO is a measure of cardiac systolic function
Time frame: Baseline and Week 65
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup
GLS by ECHO is a measure of cardiac systolic function
Time frame: Baseline and Week 65
Change From Baseline in Transthyretin (TTR) Level at Week 65
Time frame: Baseline and Week 65
Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65
Time frame: Baseline and Week 65
Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65
Time frame: Week 65
Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65
Time frame: Week 65
Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65
Time frame: Week 65
Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65
Time frame: Week 65
Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65
Time frame: Week 65
Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65
Time frame: Week 65

Results

Posted Jan 23, 2019

Participant flow

Participant flow — Overall Study
Milestone	Inotersen	Placebo
Started	113	60
Received at least 1 dose of study drug	112	60
Safety set	112	60
Completed	87	52
Not completed	26	8
Withdrew: Adverse event or sae	16	1
Withdrew: Stopping rule met	2	1
Withdrew: Voluntary withdrawal	2	3
Withdrew: Ineligibility	1	0
Withdrew: Liver transplant	1	0
Withdrew: Disease progression	2	3
Withdrew: Sponsor's decision	2	0

Outcome measures

PrimaryChange From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66

The mNIS+7 composite score is a measure of neurologic impairment that evaluates muscle weakness, sensation, reflexes, nerve conduction, and autonomic function. The mNIS+7 Composite Score has a range of -22.32 to 346.32 and a higher mNIS+7 composite score indicates lower function.

Time frame:: Baseline and Week 66
Reported as:: Mean · Scores on a Scale

Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66
Scores on a Scale	Inotersen	Placebo
Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66	4.16 ± 15.672	23.89 ± 24.190

Statistical analysis

Inotersen vs Placebo · MMRM · p = 0.00000004 · Least square mean difference: -19.73 · 95% CI -26.43 to -13.03

PrimaryChange From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66

The Norfolk QoL-DN score is a measure of physical function/large fiber neuropathy, symptoms, activities of daily living, small fiber neuropathy, and autonomic neuropathy. The Norfolk QoL-DN total score has a range of -4 to 136, and a higher Norfolk QoL-DN score indicates poorer QoL.

Time frame:: Baseline and Week 66
Reported as:: Mean · Scores on a Scale

Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66
Scores on a Scale	Inotersen	Placebo
Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66	-0.08 ± 18.967	10.77 ± 21.134

Statistical analysis

Inotersen vs Placebo · MMRM · p = 0.0006 · Least square mean difference: -11.68 · 95% CI -18.29 to -5.06

SecondaryChange From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66

The Norfolk QoL-DN symptoms score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN symptoms domain score has a range of 0-32, and a higher Norfolk QoL-DN score indicates poorer QoL.

Time frame:: Baseline and Week 66
Reported as:: Mean · Scores on a Scale

Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66
Scores on a Scale	Inotersen	Placebo
Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66	-1.40 ± 4.763	1.18 ± 5.270

SecondaryChange From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66

The Norfolk QoL-DN physical functioning/large fiber neuropathy domain score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN physical function/large fiber neuropathy domain score has a range of -4 to 56, and a higher Norfolk QoL-DN domain score indicates poorer QoL.

Time frame:: Baseline and Week 66
Reported as:: Mean · Scores on a Scale

Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66
Scores on a Scale	Inotersen	Placebo
Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66	1.05 ± 11.924	8.74 ± 9.689

SecondaryChange From Baseline In Modified Body Mass Index (mBMI) at Week 65

The mBMI is the BMI multiplied by the serum albumin g/L

Time frame:: Baseline and Week 65
Reported as:: Mean · kg/m^2*g/L

Change From Baseline In Modified Body Mass Index (mBMI) at Week 65
kg/m^2*g/L	Inotersen	Placebo
Change From Baseline In Modified Body Mass Index (mBMI) at Week 65	-73.32 ± 96.311	-85.21 ± 91.259

SecondaryChange From Baseline In Body Mass Index (BMI) at Week 65

Time frame:: Baseline and Week 65
Reported as:: Mean · kg/m^2

Change From Baseline In Body Mass Index (BMI) at Week 65
kg/m^2	Inotersen	Placebo
Change From Baseline In Body Mass Index (BMI) at Week 65	-0.24 ± 1.521	-0.87 ± 1.202

SecondaryChange From Baseline in Neuropathy Impairment Score (NIS) at Week 66

The NIS score is a measure of neurologic impairment. The NIS Score has a range of 0 to 244 and a higher NIS score indicates lower function.

Time frame:: Baseline and Week 66
Reported as:: Mean · Scores on a Scale

Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66
Scores on a Scale	Inotersen	Placebo
Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66	4.47 ± 10.329	17.29 ± 16.986

SecondaryChange From Baseline in Modified +7 at Week 66

The Modified +7 score is a version of the NIS score that is a measure of neurologic impairment. The Modified +7 Score has a range of -22.32 to 102.32 and a higher NIS score indicates lower function.

Time frame:: Baseline and Week 66
Reported as:: Mean · Scores on a Scale

Change From Baseline in Modified +7 at Week 66
Scores on a Scale	Inotersen	Placebo
Change From Baseline in Modified +7 at Week 66	-0.31 ± 11.134	6.60 ± 12.770

SecondaryChange From Baseline in NIS+7 at Week 66

The NIS+7 score is a version of the NIS score that is a measure of neurologic impairment. The NIS+7 Score has a range of -26.04 to 270.04 and a higher NIS score indicates lower function.

Time frame:: Baseline and Week 66
Reported as:: Mean · Scores on a Scale

Change From Baseline in NIS+7 at Week 66
Scores on a Scale	Inotersen	Placebo
Change From Baseline in NIS+7 at Week 66	5.10 ± 10.709	19.00 ± 16.824

SecondaryChange From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set

GLS by ECHO is a measure of cardiac systolic function

Time frame:: Baseline and Week 65
Reported as:: Mean · Percent Change

Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set
Percent Change	Inotersen	Placebo
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set	0.69 ± 3.134	0.46 ± 2.702

SecondaryChange From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup

GLS by ECHO is a measure of cardiac systolic function

Time frame:: Baseline and Week 65
Reported as:: Mean · Percent Change

Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup
Percent Change	Inotersen	Placebo
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup	0.25 ± 3.163	1.05 ± 2.745

SecondaryChange From Baseline in Transthyretin (TTR) Level at Week 65

Time frame:: Baseline and Week 65
Reported as:: Mean · g/L

Change From Baseline in Transthyretin (TTR) Level at Week 65
g/L	Inotersen	Placebo
Change From Baseline in Transthyretin (TTR) Level at Week 65	-0.1570 ± 0.0619	-0.0146 ± 0.0402

SecondaryChange From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65

Time frame:: Baseline and Week 65
Reported as:: Mean · ug/L

Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65
ug/L	Inotersen	Placebo
Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65	-21725.9 ± 9884.04	-1768.7 ± 8027.78

SecondaryMaximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65

Time frame:: Week 65
Reported as:: Mean · ug/mL

Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65
ug/mL	Inotersen 300 mg IM Negative	Inotersen 300 mg IM Positive
Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65	6.76 ± 1.88	11.1 ± 4.80

SecondaryTime To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65

Time frame:: Week 65
Reported as:: Mean · hours

Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65
hours	Inotersen 300 mg IM Negative	Inotersen 300 mg IM Positive
Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65	4.14 ± 1.88	3.48 ± 0.68

SecondaryArea Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65

Time frame:: Week 65
Reported as:: Mean · ug*hr/mL

Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65
ug*hr/mL	Inotersen 300 mg IM Negative	Inotersen 300 mg IM Positive
Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65	93.1 ± 30.7	92.4 ± 77.3

SecondaryArea Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65

Time frame:: Week 65
Reported as:: Mean · ug*hr/mL

Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65
ug*hr/mL	Inotersen 300 mg IM Negative	Inotersen 300 mg IM Positive
Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65	98.9 ± 33.5	103.0 ± 88.2

SecondaryPlasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65

Time frame:: Week 65
Reported as:: Mean · L/hr

Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65
L/hr	Inotersen 300 mg IM Negative	Inotersen 300 mg IM Positive
Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65	3.57 ± 1.32	6.14 ± 5.92

SecondaryInotersen Plasma Clearance At Steady State (CLss/F) At Week 65

Time frame:: Week 65
Reported as:: Mean · L/hr

Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65
L/hr	Inotersen 300 mg IM Negative	Inotersen 300 mg IM Positive
Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65	3.33 ± 1.21	5.46 ± 5.13

Adverse events

Collected over Week 1 to Week 91. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Inotersen	5/112 (4.5%)	36/112 (32.1%)	110/112 (98.2%)
Placebo	0/60 (0%)	13/60 (21.7%)	60/60 (100%)

Most frequent serious events

Showing 10 of 60

Most frequent serious events
Event	Inotersen	Placebo
Cardiac failure congestiveCardiac disorders	4/112	2/60
PneumoniaInfections and infestations	2/112	2/60
Ankle fractureInjury, poisoning and procedural complications	0/112	2/60
DehydrationMetabolism and nutrition disorders	3/112	0/60
BronchitisInfections and infestations	2/112	0/60
Cardiac failureCardiac disorders	2/112	1/60
Cardiac failure acuteCardiac disorders	2/112	0/60
Sinus arrestCardiac disorders	2/112	0/60
CachexiaMetabolism and nutrition disorders	2/112	0/60
Confusional statePsychiatric disorders	2/112	0/60

Most frequent other events

Showing 10 of 70

Most frequent other events
Event	Inotersen	Placebo
NauseaGastrointestinal disorders	35/112	7/60
Injection site erythemaGeneral disorders	35/112	0/60
FatigueGeneral disorders	28/112	12/60
DiarrhoeaGastrointestinal disorders	27/112	12/60
HeadacheNervous system disorders	26/112	7/60
FallInjury, poisoning and procedural complications	19/112	13/60
Injection site painGeneral disorders	23/112	4/60
PyrexiaGeneral disorders	22/112	5/60
Oedema peripheralGeneral disorders	21/112	6/60
Urinary tract infectionInfections and infestations	21/112	11/60

Baseline characteristics

Safety Set: Participants who were randomized and received at least 1 dose of study drug (inotersen or placebo). The Safety Set is the population used for the analyses of all safety measures.

Age, Continuous
Age, Continuous(years)	Inotersen	Placebo	Total
Mean	59.0 ± 12.53	59.5 ± 14.05	59.2 ± 13.04

Sex: Female, Male
Sex: Female, Male(Participants)	Inotersen	Placebo	Total
Female	35	19	54
Male	77	41	118

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Inotersen	Placebo	Total
Hispanic or Latino	17	7	24
Not Hispanic or Latino	95	53	148
Unknown or Not Reported	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Inotersen	Placebo	Total
Asian	1	3	4
Black	3	1	4
White	105	53	158
White & Grayish-Brown	0	1	1
Other	3	2	5

Participants diagnosed with hATTR-CM
Participants diagnosed with hATTR-CM(Participants)	Inotersen	Placebo	Total
Yes	45	22	67
No	67	38	105

Study locations

24 sites

University of California, Irvine
Orange, California 92868, United States
Indiana University School of Medicine
Indianapolis, Indiana 46202, United States
Johns Hopkins University Bayview Medical Center
Baltimore, Maryland 21205, United States
Boston University School of Medicine - Amyloid Treatment & Research Program
Boston, Massachusetts 02118, United States
Mayo Clinic
Rochester, Minnesota 55905, United States
Mount Sinai Medical Center
New York, New York 10029, United States
Columbia University Medical Center - The Neurological Institute
New York, New York 10032, United States
Oregon Health & Science University
Portland, Oregon 97239, United States
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania 19104, United States
FLENI
Buenos Aires, Argentina
Federal University of Rio de Janeiro - University Hospital
Rio de Janeiro, CEP 21941913, Brazil
AACD
Sao Paulo, Brazil
UNIFESP
Sao Paulo, Brazil
CHU Henri Mondor - Department of Neurology
Creteil, 94000, France
CHU Bicetre Aphp French Referral Center for FAP/Cornamyl Network
Le Kremlin Bicetre, 94275, France
UKM; Universitätsklinikum Münster, Klinik für Transplantationsmedizin
Munster, 48149, Germany
Universita Degli Studi Di Messina - Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino"
Messina, Sicily 98124, Italy
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico San Matteo
Pavia, 27100, Italy
Auckland City Hospital
Auckland, New Zealand
CHLN - Hospital de Santa Maria
Lisbon, 1649-035, Portugal
CHP-HGSA, Unidade Clinica de Paramiloidose
Porto, 4099-001, Portugal
Hospital Universitari Vall D' Hebron
Barcelona, 08035, Spain
Hospital Clínic
Barcelona, 08036, Spain
University College London - National Amyloidosis Centre
London, NW3 2PF, United Kingdom

References and documents

Publications

Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Plante-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceicao I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793. PubMed 29972757 ↗
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Dyck PJB, Coelho T, Waddington Cruz M, Brannagan TH 3rd, Khella S, Karam C, Berk JL, Polydefkis MJ, Kincaid JC, Wiesman JF, Litchy WJ, Mauermann ML, Ackermann EJ, Baker BF, Jung SW, Guthrie S, Pollock M, Dyck PJ. Neuropathy symptom and change: Inotersen treatment of hereditary transthyretin amyloidosis. Muscle Nerve. 2020 Oct;62(4):509-515. doi: 10.1002/mus.27023. Epub 2020 Aug 7. PubMed 32654156 ↗
Coelho T, Yarlas A, Waddington-Cruz M, White MK, Sikora Kessler A, Lovley A, Pollock M, Guthrie S, Ackermann EJ, Hughes SG, Karam C, Khella S, Gertz M, Merlini G, Obici L, Schmidt HH, Polydefkis M, Dyck PJB, Brannagan Iii TH, Conceicao I, Benson MD, Berk JL. Inotersen preserves or improves quality of life in hereditary transthyretin amyloidosis. J Neurol. 2020 Apr;267(4):1070-1079. doi: 10.1007/s00415-019-09671-9. Epub 2019 Dec 18. PubMed 31853709 ↗
Pinto MV, Dyck PJB, Gove LE, McCauley BM, Ackermann EJ, Hughes SG, Waddington-Cruz M, Dyck PJ. Kind and distribution of cutaneous sensation loss in hereditary transthyretin amyloidosis with polyneuropathy. J Neurol Sci. 2018 Nov 15;394:78-83. doi: 10.1016/j.jns.2018.08.031. Epub 2018 Aug 30. PubMed 30219500 ↗
Waddington-Cruz M, Ackermann EJ, Polydefkis M, Heitner SB, Dyck PJ, Barroso FA, Wang AK, Berk JL, Dyck PJB, Monia BP, Hughes SG, Tai L, Jesse Kwoh T, Jung SW, Coelho T, Benson MD, Gertz MA. Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial. Amyloid. 2018 Sep;25(3):180-188. doi: 10.1080/13506129.2018.1503593. Epub 2018 Aug 31. PubMed 30169969 ↗

Study documents

Study protocol · May 13, 2016
Statistical analysis plan · Apr 21, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 17, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01737398
Lead sponsor: Ionis Pharmaceuticals, Inc.
Responsible party: Sponsor
First posted: Nov 29, 2012
Start date: Mar 15, 2013
Primary completion: Mar 3, 2017
Completion: Nov 7, 2017
Results posted: Jan 23, 2019
Last update: Jul 17, 2019

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2019. You cannot join it, but the record below documents what was studied.

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Discussion

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