Familial Amyloid Polyneuropathy MedDRA version: 19.0 Level: LLT Classification code 10057949 Term: Familial amyloid polyneuropathy System Organ Class: 100000004850
Conditions
Interventions
Product Name: Human Transthyretin Antisense Oligonucleotide
Product Code: ISIS 420915
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ISIS 420915
Current Sponsor code: ISIS 420915
Con
Sponsors
Ionis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosed Stage 1 or Stage 2 FAP patient • Meets NIS requirements • Male or female aged 18 to 82 years old at the time of informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: • Has inadequate liver, renal or heart function • Has retinol levels at screen < LLN • Has human immunodeficiency virus (HIV), hepatitis B or hepatitis C • Has type 1 or type 2 diabetes mellitus or other cause of sensorimotor or autonomic neuropathy • Recently treated with another investigational drug, biological agent or device • Is currently taking Vyndaqel® or diflunisal • Prior liver transplant or anticipated liver transplant within 1 year of screening • Anticipated survival less than 2 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ISIS 420915 as compared to placebo, given for 65 weeks, as measured by the change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire total score, in patients with Familial Amyloid Polyneuropathy (FAP).;Secondary Objective: To evaluate the efficacy of ISIS 420915 as compared to placebo based on the change from baseline in the following measures: • Norfolk QOL-DN questionnaire symptoms domain score in Stage 1 patients and Norfolk QOL-DN questionnaire physical functioning/large fiber neuropathy domain score in Stage 2 patients • Modified body mass index (mBMI) and body mass index (BMI) • NIS and modified +7 • NIS+7 • Global longitudinal strain (GLS) by echocardiogram (ECHO) in the ECHO subgroup and in the Cardiomyopathy-ECHO (CM-ECHO) Set To evaluate the pharmacodynamic (PD) effect of ISIS 420915 as compared to placebo, based on the change from baseline in transthyretin (TTR) and retinol binding protein 4 (RBP4). To evaluate the safety and tolerability of ISIS 420915. To evaluate the plasma trough levels of ISIS 420915 in all patients and to evaluate the plasma pharmacokinetic parameters of ISIS 420915 in a subset of patients.;Primary end point(s): Change in mNIS+7 score from baseline to Week 66 and the change in the Norfolk QOL-DN questionnaire total score from baseline to Week 66;Timepoint(s) of evaluation of this end point: 66 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in the Norfolk QOL-DN questionnaire symptoms domain score (Stage 1 patients only) and Norfolk QOL-DN questionnaire physical functioning/large fiber neuropathy domain score (Stage 2 patients only) from baseline to Week 66 • Change in the mBMI and BMI from baseline to Week 65 • Change in NIS and modified +7 from baseline to Week 66 • Change in NIS+7 score from baseline to Week 66 • Changes in Global longitudinal strain (GLS) by echocardiogram (ECHO) in the ECHO subgroup and in the Cardiomyopathy-ECHO (CM-ECHO) Set ;Timepoint(s) of evaluation of this end point: 66 Weeks | — |
Countries
Argentina, Brazil, Bulgaria, France, Germany, Italy, New Zealand, Portugal, Spain, United Kingdom, United States
Contacts
Public ContactMatt R. Buck
Ionis Pharmaceuticals, Inc.
Outcome results
None listed