FAPPhase 2/3NCT01737398
Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy
A Phase 2/3 study testing Inotersen in people with FAP and Familial Amyloid Polyneuropathy, run by Ionis Pharmaceuticals, Inc. at 24 sites in 10 countries.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 82 years
- Conditions the study is for
- FAP, Familial Amyloid Polyneuropathy, TTR
- What is being tested?
- Inotersen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 173 participants
- Where
- 24 sitesin 10 countries
- Study dates
- 15 Mar 2013to 7 Nov 2017
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 82 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stage 1 and Stage 2 FAP participants with the following:
- NIS score within protocol criteria
- Documented transthyretin variant by genotyping
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
24 sites in 10 countries.
24 sites in 10 countries
United States9 sites
Johns Hopkins University Bayview Medical Center
Baltimore, Maryland, 21205
Boston University School of Medicine - Amyloid Treatment & Research Program
Boston, Massachusetts, 02118
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Mount Sinai Medical Center
New York, New York, 10029
Columbia University Medical Center - The Neurological Institute
New York, New York, 10032
University of California, Irvine
Orange, California, 92868
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
Brazil3 sites
Federal University of Rio de Janeiro - University Hospital
Rio de Janeiro, CEP 21941913
AACD
São Paulo
UNIFESP
São Paulo
France2 sites
CHU Henri Mondor - Department of Neurology
Créteil, 94000
CHU Bicetre Aphp French Referral Center for FAP/Cornamyl Network
Le Kremlin-Bicêtre, 94275
Italy2 sites
Universita Degli Studi Di Messina - Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino"
Messina, Sicily, 98124
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Portugal2 sites
CHLN - Hospital de Santa Maria
Lisbon, 1649-035
CHP-HGSA, Unidade Clinica de Paramiloidose
Porto, 4099-001
Spain2 sites
Hospital Universitari Vall D' Hebron
Barcelona, 08035
Hospital Clínic
Barcelona, 08036
Germany1 site
UKM; Universitätsklinikum Münster, Klinik für Transplantationsmedizin
Münster, 48149
United Kingdom1 site
University College London - National Amyloidosis Centre
London, NW3 2PF
About this study
Official title: A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (NEURO-TTR Study)
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
- FAP, Familial Amyloid Polyneuropathy, TTR, Transthyretin, Amyloidosis
- Being tested
- Inotersen, Placebo
- Keywords
- FAP, Familial Amyloid Polyneuropathy, TTR, Transthyretin, Amyloidosis
- Medical subject headings
- Amyloid Neuropathies, Familial, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InotersenDrug
Also called TEGSEDI, IONIS-TTR Rx, ISIS 420915
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Inotersen | Active comparator | 300 mg inotersen administered subcutaneously (SC) 3 times on alternate days in the first week and then once-weekly for 64 weeks Receives: Drug: Inotersen |
| Placebo | Active comparator | Placebo administered SC 3 times on alternate days in the first week and then once-weekly for 64 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline and Week 66
Secondary outcomes (17)
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.
Measured: 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.
Measured: 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
Measured: Baseline and Week 65
Change From Baseline In Body Mass Index (BMI) at Week 65
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: Baseline and Week 65
Change From Baseline in Transthyretin (TTR) Level at Week 65
Measured: Baseline and Week 65
Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65
Measured: Baseline and Week 65
Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65
Measured: Week 65
Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65
Measured: Week 65
Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65
Measured: Week 65
Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65
Measured: Week 65
Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65
Measured: Week 65
Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65
Measured: Week 65
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2012 (estimated)
- Study start15 Mar 2013
- Primary completion3 Mar 2017
- Study completion7 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for FAPStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 173 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01737398
- Sponsor's protocol ID
- ISIS 420915-CS2
- Status last verified
- Jul 2019
- First submitted
- 27 Nov 2012
- Last updated
- 17 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
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 29972757Waddington Cruz M, Berk JL, Parman Y, Gertz M, Khella S, Weiler M, Kwoh TJ, Pola M, Reicher B, Natman J, Dasgupta NR, Wixner J. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients. Muscle Nerve. 2026 Jun;73(6):1118-1127. doi: 10.1002/mus.70230. Epub 2026 Apr 6.
PubMed 41937511Gillmore JD, Adams D, Weiler M, Masri A, Obici L, Natman J, Kwoh TJ, Reicher B, Revkin J, Cruz MW, Gertz M, Chao CC. Effect of Eplontersen in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy Across Genetic Variants: An Exploratory Analysis From the NEURO-TTRansform Trial. Eur J Neurol. 2026 Apr;33(4):e70580. doi: 10.1111/ene.70580.
PubMed 41913562Masri A, Maurer MS, Claggett BL, Kulac I, Waddington Cruz M, Conceicao I, Weiler M, Berk JL, Gertz M, Gillmore JD, Rush S, Chen J, Zhou W, Kwoh J, Duran JM, Tsimikas S, Solomon SD. Effect of Eplontersen on Cardiac Structure and Function in Patients With Hereditary Transthyretin Amyloidosis. J Card Fail. 2024 Aug;30(8):973-980. doi: 10.1016/j.cardfail.2023.11.016. Epub 2023 Dec 7.
PubMed 38065307Karam C, Brown D, Yang M, Done N, Zhu JJ, Greatsinger A, Bozas A, Vera-Llonch M, Signorovitch J. Long-term treatment effects of inotersen on health-related quality of life in patients with hATTR amyloidosis with polyneuropathy: Analysis of the open-label extension of the NEURO-TTR trial. Muscle Nerve. 2022 Oct;66(4):438-446. doi: 10.1002/mus.27675. Epub 2022 Aug 4.
PubMed 35799473Karam C, Brown D, Yang M, Done N, Dieye I, Bozas A, Vera Llonch M, Signorovitch J. Factors associated with increased health-related quality-of-life benefits in hereditary transthyretin amyloidosis polyneuropathy patients treated with inotersen. Muscle Nerve. 2022 Sep;66(3):319-328. doi: 10.1002/mus.27668. Epub 2022 Jul 15.
PubMed 35766224Yarlas A, Lovley A, McCausland K, Brown D, Vera-Llonch M, Conceicao I, Karam C, Khella S, Obici L, Waddington-Cruz M. Early Data on Long-term Impact of Inotersen on Quality-of-Life in Patients with Hereditary Transthyretin Amyloidosis Polyneuropathy: Open-Label Extension of NEURO-TTR. Neurol Ther. 2021 Dec;10(2):865-886. doi: 10.1007/s40120-021-00268-x. Epub 2021 Aug 5.
PubMed 34355354Yarlas A, Lovley A, Brown D, Kosinski M, Vera-Llonch M. Responder analysis for neuropathic impairment and quality-of-life assessment in patients with hereditary transthyretin amyloidosis with polyneuropathy in the NEURO-TTR study. J Neurol. 2022 Jan;269(1):323-335. doi: 10.1007/s00415-021-10635-1. Epub 2021 Jun 14.
PubMed 34125267Yu RZ, Wang Y, Norris DA, Kim TW, Narayanan P, Geary RS, Monia BP, Henry SP. Immunogenicity Assessment of Inotersen, a 2'-O-(2-Methoxyethyl) Antisense Oligonucleotide in Animals and Humans: Effect on Pharmacokinetics, Pharmacodynamics, and Safety. Nucleic Acid Ther. 2020 Oct;30(5):265-275. doi: 10.1089/nat.2020.0867. Epub 2020 Aug 19.
PubMed 32833564Dyck PJB, Kincaid JC, Wiesman JF, Polydefkis M, Litchy WJ, Mauermann ML, Ackermann EJ, Guthrie S, Pollock M, Jung SW, Baker BF, Dyck PJ. mNIS+7 and lower limb function in inotersen treatment of hereditary transthyretin-mediated amyloidosis. Muscle Nerve. 2020 Oct;62(4):502-508. doi: 10.1002/mus.27022. Epub 2020 Aug 13.
PubMed 32654212Dyck 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 32654156Coelho 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 31853709Pinto 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 30219500Waddington-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 at a glance
From the registry record, last updated by the sponsor on 17 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (NEURO-TTR Study)
- ClinicalTrials.gov ID
- NCT01737398
- Acronym / sponsor ID
- ISIS 420915-CS2
- Conditions
- FAP, Familial Amyloid Polyneuropathy, TTR, Transthyretin, Amyloidosis
- Keywords
- FAP, Familial Amyloid Polyneuropathy, TTR, Transthyretin, Amyloidosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 173 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Mar 2013 (actual)
- Primary completion
- 3 Mar 2017 (actual)
- Study completion
- 7 Nov 2017 (actual)
- First posted
- 29 Nov 2012 (estimated)
- Results
- Posted 23 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inotersen | Active comparator | Drug: Inotersen300 mg inotersen administered subcutaneously (SC) 3 times on alternate days in the first week and then once-weekly for 64 weeks |
| Placebo | Active comparator | Drug: PlaceboPlacebo administered SC 3 times on alternate days in the first week and then once-weekly for 64 weeks |
Who may qualify
- Ages
- 18 to 82 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Stage 1 and Stage 2 FAP participants with the following:
- 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
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InotersenAlso: TEGSEDI, IONIS-TTR Rx, ISIS 420915 | Drug | Inotersen |
| Placebo | Drug | Placebo |
Primary outcome
Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66
Time frame: Baseline and 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.
Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66
Time frame: Baseline and 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.
17 secondary outcomes
Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66
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
Time frame: Baseline and Week 66
Change From Baseline In Modified Body Mass Index (mBMI) at Week 65
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
Time frame: Baseline and Week 66
Change From Baseline in Modified +7 at Week 66
Time frame: Baseline and Week 66
Change From Baseline in NIS+7 at Week 66
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
Time frame: Baseline and Week 65
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup
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 and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29972757Benson 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.
- Derived from this study: PubMed 41937511Waddington Cruz M, Berk JL, Parman Y, Gertz M, Khella S, Weiler M, Kwoh TJ, Pola M, Reicher B, Natman J, Dasgupta NR, Wixner J. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients. Muscle Nerve. 2026 Jun;73(6):1118-1127. doi: 10.1002/mus.70230. Epub 2026 Apr 6.
- Derived from this study: PubMed 41913562Gillmore JD, Adams D, Weiler M, Masri A, Obici L, Natman J, Kwoh TJ, Reicher B, Revkin J, Cruz MW, Gertz M, Chao CC. Effect of Eplontersen in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy Across Genetic Variants: An Exploratory Analysis From the NEURO-TTRansform Trial. Eur J Neurol. 2026 Apr;33(4):e70580. doi: 10.1111/ene.70580.
- Derived from this study: PubMed 38065307Masri A, Maurer MS, Claggett BL, Kulac I, Waddington Cruz M, Conceicao I, Weiler M, Berk JL, Gertz M, Gillmore JD, Rush S, Chen J, Zhou W, Kwoh J, Duran JM, Tsimikas S, Solomon SD. Effect of Eplontersen on Cardiac Structure and Function in Patients With Hereditary Transthyretin Amyloidosis. J Card Fail. 2024 Aug;30(8):973-980. doi: 10.1016/j.cardfail.2023.11.016. Epub 2023 Dec 7.
- Derived from this study: PubMed 35799473Karam C, Brown D, Yang M, Done N, Zhu JJ, Greatsinger A, Bozas A, Vera-Llonch M, Signorovitch J. Long-term treatment effects of inotersen on health-related quality of life in patients with hATTR amyloidosis with polyneuropathy: Analysis of the open-label extension of the NEURO-TTR trial. Muscle Nerve. 2022 Oct;66(4):438-446. doi: 10.1002/mus.27675. Epub 2022 Aug 4.
- Derived from this study: PubMed 35766224Karam C, Brown D, Yang M, Done N, Dieye I, Bozas A, Vera Llonch M, Signorovitch J. Factors associated with increased health-related quality-of-life benefits in hereditary transthyretin amyloidosis polyneuropathy patients treated with inotersen. Muscle Nerve. 2022 Sep;66(3):319-328. doi: 10.1002/mus.27668. Epub 2022 Jul 15.
- Derived from this study: PubMed 34355354Yarlas A, Lovley A, McCausland K, Brown D, Vera-Llonch M, Conceicao I, Karam C, Khella S, Obici L, Waddington-Cruz M. Early Data on Long-term Impact of Inotersen on Quality-of-Life in Patients with Hereditary Transthyretin Amyloidosis Polyneuropathy: Open-Label Extension of NEURO-TTR. Neurol Ther. 2021 Dec;10(2):865-886. doi: 10.1007/s40120-021-00268-x. Epub 2021 Aug 5.
- Derived from this study: PubMed 34125267Yarlas A, Lovley A, Brown D, Kosinski M, Vera-Llonch M. Responder analysis for neuropathic impairment and quality-of-life assessment in patients with hereditary transthyretin amyloidosis with polyneuropathy in the NEURO-TTR study. J Neurol. 2022 Jan;269(1):323-335. doi: 10.1007/s00415-021-10635-1. Epub 2021 Jun 14.
- Derived from this study: PubMed 32833564Yu RZ, Wang Y, Norris DA, Kim TW, Narayanan P, Geary RS, Monia BP, Henry SP. Immunogenicity Assessment of Inotersen, a 2'-O-(2-Methoxyethyl) Antisense Oligonucleotide in Animals and Humans: Effect on Pharmacokinetics, Pharmacodynamics, and Safety. Nucleic Acid Ther. 2020 Oct;30(5):265-275. doi: 10.1089/nat.2020.0867. Epub 2020 Aug 19.
- Derived from this study: PubMed 32654212Dyck PJB, Kincaid JC, Wiesman JF, Polydefkis M, Litchy WJ, Mauermann ML, Ackermann EJ, Guthrie S, Pollock M, Jung SW, Baker BF, Dyck PJ. mNIS+7 and lower limb function in inotersen treatment of hereditary transthyretin-mediated amyloidosis. Muscle Nerve. 2020 Oct;62(4):502-508. doi: 10.1002/mus.27022. Epub 2020 Aug 13.
- Derived from this study: PubMed 32654156Dyck 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.
- Derived from this study: PubMed 31853709Coelho 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Inotersen in people with FAP and Familial Amyloid Polyneuropathy, run by Ionis Pharmaceuticals, Inc. at 24 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Brazil, France, Italy, Portugal and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66 (time frame: Baseline and Week 66). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01737398, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2019.