Phase 3
Completed N=173
Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy
FAP · Familial Amyloid Polyneuropathy · TTR · Transthyretin
Source: ClinicalTrials.gov NCT01737398 ↗
Enrolled (actual)
173
Serious AEs
28.5%
Results posted
Jan 2019
Primary outcomePrimary: Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66 — 4.16; 23.89 Scores on a Scale — p=0.00000004
◆ Published Evidence
Highly cited
1,423citations · ~178 / year
Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis.
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).
Linked Publications (5)
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Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis.
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Effect of Eplontersen on Cardiac Structure and Function in Patients With Hereditary Transthyretin Amyloidosis.
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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.
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Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients.
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Effect of Eplontersen in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy Across Genetic Variants: An Exploratory Analysis From the NEURO-TTRansform Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66 |
4.16; 23.89 | 0.00000004 sig |
| PRIMARY Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66 |
-0.08; 10.77 | 0.0006 sig |
| SECONDARY Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66 |
-1.40; 1.18 | — |
| SECONDARY Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66 |
1.05; 8.74 | — |
| SECONDARY Change From Baseline In Modified Body Mass Index (mBMI) at Week 65 |
-73.32; -85.21 | — |
| SECONDARY Change From Baseline In Body Mass Index (BMI) at Week 65 |
-0.24; -0.87 | — |
| SECONDARY Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66 |
4.47; 17.29 | — |
| SECONDARY Change From Baseline in Modified +7 at Week 66 |
-0.31; 6.60 | — |
| SECONDARY Change From Baseline in NIS+7 at Week 66 |
5.10; 19.00 | — |
| SECONDARY Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set |
0.69; 0.46 | — |
| SECONDARY Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup |
0.25; 1.05 | — |
| SECONDARY Change From Baseline in Transthyretin (TTR) Level at Week 65 |
-0.1570; -0.0146 | — |
| SECONDARY Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65 |
-21725.9; -1768.7 | — |
| SECONDARY Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65 |
6.76; 11.1 | — |
| SECONDARY Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65 |
4.14; 3.48 | — |
| SECONDARY Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65 |
93.1; 92.4 | — |
| SECONDARY Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65 |
98.9; 103.0 | — |
| SECONDARY Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65 |
3.57; 6.14 | — |
| SECONDARY Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65 |
3.33; 5.46 | — |
Eligibility Criteria
Inclusion Criteria
- 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
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
Data sourced from ClinicalTrials.gov (NCT01737398) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.