Overview

This trial is active, not recruiting.

Conditions fap, familial amyloid polyneuropathy, ttr, transthyretin, amyloidosis
Treatments ionis-ttr rx, placebo
Phase phase 3
Sponsor Ionis Pharmaceuticals, Inc.
Collaborator GlaxoSmithKline
Start date December 2012
End date March 2017
Trial size 172 participants
Trial identifier NCT01737398, ISIS 420915-CS2

Summary

The purpose of this study is to evaluate the efficacy and safety of IONIS-TTR Rx given for 65 weeks in patients with Familial Amyloid Polyneuropathy

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
ionis-ttr rx
300 mg IONIS-TTR Rx administered subcutaneously 3 times on alternate days in the first week and then once-weekly for 64 weeks.
(Active Comparator)
placebo
Placebo administered subcutaneously 3 times on alternate days in the first week and then once-weekly for 64 weeks.

Primary Outcomes

Measure
Efficacy of IONIS-TTR Rx as measured by change from baseline in the modified Neuropathy Impairment Score +7
time frame: 65 weeks
Efficacy of IONIS-TTR Rx as measured by change from baseline in the Norfolk Quality of Life Diabetic Neuropathy questionnaire
time frame: 65 weeks

Secondary Outcomes

Measure
Efficacy of IONIS-TTR Rx based on the change from baseline in the following measures:
time frame: 65 weeks
Pharmacodynamic effect of IONIS-TTR Rx based on the change from baseline in transthyretin and retinol binding protein 4
time frame: 65 weeks

Eligibility Criteria

Male or female participants from 18 years up to 82 years old.

Inclusion Criteria: - Stage 1 and Stage 2 FAP patients 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 must be non-pregnant and non-lactating. Males engaged in relations of child-bearing potential must 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 (e.g., autoimmune disease) - If previously treated with Vyndaqel®, must have discontinued treatment for 2 weeks prior to Study Day 1. If previously treated with Diflunisal, must 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 yr 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 - Have any other conditions in the opinion of the investigator which could interfere with the patient participating in or completing the study

Additional Information

Official title A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy
Description Familial Amyloid Polyneuropathy (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. IONIS-TTR Rx is an antisense drug that is designed to decrease the amount of mutant and normal TTR made by the liver. It is predicted that decreasing the amount of TTR protein will 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 IONIS-TTR Rx can slow or stop the nerve damage caused by TTR deposits. This study will enroll late Stage 1 and early Stage 2 FAP patients. Patients will receive either IONIS-TTR Rx or placebo for 65 weeks.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Ionis Pharmaceuticals, Inc..