Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy

Ionis Pharmaceuticals, Inc.173 enrolled

Overview

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).

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

173

Conditions

FAP Familial Amyloid Polyneuropathy TTR Transthyretin Amyloidosis

Interventions

InotersenDRUG

PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 82 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Stage 1 and Stage 2 FAP participants with the following: 1. NIS score within protocol criteria 2. Documented transthyretin variant by genotyping 3. 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

Locations (24)

University of California, Irvine

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Baseline and Week 66

Secondary Outcomes

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.

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

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.

Time frame: 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

Data from ClinicalTrials.gov

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