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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01737398




Registration number
NCT01737398
Ethics application status
Date submitted
27/11/2012
Date registered
29/11/2012

Titles & IDs
Public title
Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy
Scientific 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 (NEURO-TTR Study)
Secondary ID [1] 0 0
ISIS 420915-CS2
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
FAP 0 0
Familial Amyloid Polyneuropathy 0 0
TTR 0 0
Transthyretin 0 0
Amyloidosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Neurodegenerative diseases
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Active comparator: Inotersen - 300 mg inotersen administered subcutaneously (SC) 3 times on alternate days in the first week and then once-weekly for 64 weeks

Active comparator: Placebo - Placebo administered SC 3 times on alternate days in the first week and then once-weekly for 64 weeks
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66
Timepoint [1] 0 0
Baseline and Week 66
Primary outcome [2] 0 0
Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66
Timepoint [2] 0 0
Baseline and Week 66
Secondary outcome [1] 0 0
Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66
Timepoint [1] 0 0
Baseline and Week 66
Secondary outcome [2] 0 0
Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66
Timepoint [2] 0 0
Baseline and Week 66
Secondary outcome [3] 0 0
Change From Baseline In Modified Body Mass Index (mBMI) at Week 65
Timepoint [3] 0 0
Baseline and Week 65
Secondary outcome [4] 0 0
Change From Baseline In Body Mass Index (BMI) at Week 65
Timepoint [4] 0 0
Baseline and Week 65
Secondary outcome [5] 0 0
Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66
Timepoint [5] 0 0
Baseline and Week 66
Secondary outcome [6] 0 0
Change From Baseline in Modified +7 at Week 66
Timepoint [6] 0 0
Baseline and Week 66
Secondary outcome [7] 0 0
Change From Baseline in NIS+7 at Week 66
Timepoint [7] 0 0
Baseline and Week 66
Secondary outcome [8] 0 0
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set
Timepoint [8] 0 0
Baseline and Week 65
Secondary outcome [9] 0 0
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup
Timepoint [9] 0 0
Baseline and Week 65
Secondary outcome [10] 0 0
Change From Baseline in Transthyretin (TTR) Level at Week 65
Timepoint [10] 0 0
Baseline and Week 65
Secondary outcome [11] 0 0
Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65
Timepoint [11] 0 0
Baseline and Week 65
Secondary outcome [12] 0 0
Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65
Timepoint [12] 0 0
Week 65
Secondary outcome [13] 0 0
Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65
Timepoint [13] 0 0
Week 65
Secondary outcome [14] 0 0
Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65
Timepoint [14] 0 0
Week 65
Secondary outcome [15] 0 0
Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65
Timepoint [15] 0 0
Week 65
Secondary outcome [16] 0 0
Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65
Timepoint [16] 0 0
Week 65
Secondary outcome [17] 0 0
Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65
Timepoint [17] 0 0
Week 65

Eligibility
Key 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
Minimum age
18 Years
Maximum age
82 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/03/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/11/2017
Sample size
Target
Accrual to date
Final
173
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Brazil
State/province [10] 0 0
Rio de Janeiro
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
France
State/province [12] 0 0
Creteil
Country [13] 0 0
France
State/province [13] 0 0
Le Kremlin Bicetre
Country [14] 0 0
Germany
State/province [14] 0 0
Munster
Country [15] 0 0
Italy
State/province [15] 0 0
Sicily
Country [16] 0 0
Italy
State/province [16] 0 0
Pavia
Country [17] 0 0
New Zealand
State/province [17] 0 0
Auckland
Country [18] 0 0
Portugal
State/province [18] 0 0
Lisbon
Country [19] 0 0
Portugal
State/province [19] 0 0
Porto
Country [20] 0 0
Spain
State/province [20] 0 0
Barcelona
Country [21] 0 0
United Kingdom
State/province [21] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ionis Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Benson MD, Waddington-Cruz M, Berk JL, Polydefkis ... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT01737398