Phase 3
N=135
Extension Study Assessing Long Term Safety and Efficacy of IONIS-TTR Rx in Familial Amyloid Polyneuropathy (FAP)
FAP · Familial Amyloid Polyneuropathy · TTR · Transthyretin · Amyloidosis
Bottom Line
View on ClinicalTrials.gov: NCT02175004 ↗Enrolled (actual)
135
Serious AEs
47.4%
Results posted
Feb 2023
Primary outcome: Primary: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Related to Study Drug — 100; 96.5; 36.0; 54.1 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Inotersen (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Primary completion
- Sep 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Related to Study Drug |
100; 96.5; 36.0; 54.1; 82.0; 69.4 | — |
| PRIMARY Percentage of Participants With Change From Baseline in Vital Signs |
12.0; 18.8; 32.0; 41.2; 8.0; 20.0 | — |
| PRIMARY Percentage of Participants With Change From Baseline in Weight |
30.0; 47.1; 24.0; 11.8 | — |
| PRIMARY Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Test Values |
4.0; 4.7; 8.0; 10.6; 4.0; 4.7 | — |
| PRIMARY Percentage of Participants With Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) as Determined by Electrocardiogram (ECG) |
44.0; 43.5; 20.0; 23.5; 12.0; 16.5 | — |
| PRIMARY Percentage of Participants Using Concomitant Medication for Nervous and Cardiovascular System Disorders |
88.0; 81.2; 68.0; 75.3 | — |
| PRIMARY Percentage of Participants With Change From Baseline in Ophthalmic Examination as Assessed by Visual Acuity Changes |
0.0; 2.4 | — |
| PRIMARY Percentage of Participants With Change From Baseline in Light Detection Ability Measured by Electroretinography |
25.0; 12.7; 31.3; 9.1 | — |
| SECONDARY Change From Baseline in the Modified Neuropathy Impairment Score (mNIS)+7 Composite Score at Weeks 78 and 156 |
33.11; 10.11; 37.34; 17.21 | <0.001 sig |
| SECONDARY Change From Baseline in the mNIS +7 Component: Heart Rate to Deep Breathing Score at Weeks 78 and 156 |
0.23; 0.11; 0.44; 0.30 | 0.638 |
| SECONDARY Change From Baseline in the mNIS +7 Component: Nerve Conduction Score at Weeks 78 and 156 |
1.86; 0.57; 2.05; 0.77 | <0.001 sig |
| SECONDARY Change From Baseline in the mNIS +7 Component: Heat-Pain Sensory Score at Weeks 78 and 156 |
2.60; 2.45; 2.90; 3.40 | 0.821 |
| SECONDARY Change From Baseline in the mNIS +7 Component: Touch-Pressure Sensory Score at Weeks 78 and 156 |
1.00; -3.05; 1.95; -2.34 | 0.047 sig |
| SECONDARY Change From Baseline in the Neuropathy Impairment (NIS) Composite Score at Week 52 of Years 4 and 5 |
35.78; 18.32; 17.75 | <0.001 sig |
| SECONDARY Change From Baseline in the NIS Component: Cranial Nerves Score at Week 52 of Years 4 and 5 |
0.0; 0.0; 0.0 | 0.941 |
| SECONDARY Change From Baseline in the NIS Component: Muscle Weakness Score at Week 52 of Years 4 and 5 |
23.67; 14.71; 13.75 | 0.011 sig |
| SECONDARY Change From Baseline in the NIS Component: Reflexes Score at Week 52 of Years 4 and 5 |
4.17; 2.32; 4.00 | 0.356 |
| SECONDARY Change From Baseline in the NIS Component: Sensory Score at Week 52 of Years 4 and 5 |
7.94; 1.29; 0.00 | <0.001 sig |
| SECONDARY Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) Questionnaire Total Score at Weeks 78 and 156 |
15.22; 3.76; 14.94; 5.98; 6.22; 2.36 | 0.026 sig |
| SECONDARY Change From Baseline in the Norfolk QoL-DN Physical Functioning/Large Fiber Neuropathy Domain Score |
11.21; 3.61; 12.60; -0.55; 9.50; 3.50 | 0.097 |
| SECONDARY Change From Baseline in the Modified Body Mass Index (mBMI) at Weeks 78 and 156 |
-166.27; -161.52; -191.68; -172.52 | — |
| SECONDARY Change From Baseline in the Body Mass Index (BMI) at Weeks 78 and 156 |
-0.16; -0.44; -0.34; -0.66 | — |
| SECONDARY Percentage of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Score |
5.6; 11.3; 69.4; 62.0; 25.0; 26.8 | — |
| SECONDARY Percent Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) in the Cardiomyopathy-ECHO (CM-ECHO) Set |
0.38; -0.74; 1.46; 0.07 | — |
| SECONDARY Percent Change From Baseline in GLS by ECHO in the CS3 ECHO Subgroup |
-6.93; 8.99; -2.79; 11.46 | — |
| SECONDARY Change From Baseline in Transthyretin (TTR) Level |
-0.1581; -0.1555; -0.1498; -0.1692 | — |
| SECONDARY Change From Baseline in Retinol Binding Protein 4 (RBP4) Level |
-21073.1; -19365.9; -21489.4; -22372.3; -28307.1; -24893.7 | — |
| SECONDARY Ctrough: Trough Plasma Concentration of ISIS 420915 |
NA; 34.1; 22.9; 74.0; 28.6; 83.0 | — |
Summary
This study evaluates the safety and tolerability of extended dosing with IONIS-TTR Rx in patients with Familial Amyloid Polyneuropathy.
Eligibility Criteria
Inclusion Criteria
- Satisfactory completion of dosing & efficacy assessments in ISIS 420915-CS2
Exclusion Criteria
- Any new condition or worsening of existing condition that could make the patient unsuitable for participation, or interfere with the patient participating in and/or completing the study
Data sourced from ClinicalTrials.gov (NCT02175004). 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.