Phase 3
N=173
Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy
FAP · Familial Amyloid Polyneuropathy · TTR · Transthyretin · Amyloidosis
Bottom Line
View on ClinicalTrials.gov: NCT01737398 ↗Enrolled (actual)
173
Serious AEs
28.5%
Results posted
Jan 2019
Primary outcome: Primary: 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
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Inotersen (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Primary completion
- Mar 2017
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 | — |
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).
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). 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.