Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01737398
Registration number
NCT01737398
Ethics application status
Date submitted
27/11/2012
Date registered
29/11/2012
Date last updated
17/07/2019
Titles & IDs
Public title
Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy
Query!
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)
Query!
Secondary ID [1]
0
0
ISIS 420915-CS2
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
FAP
0
0
Query!
Familial Amyloid Polyneuropathy
0
0
Query!
TTR
0
0
Query!
Transthyretin
0
0
Query!
Amyloidosis
0
0
Query!
Condition category
Condition code
Neurological
0
0
0
0
Query!
Other neurological disorders
Query!
Neurological
0
0
0
0
Query!
Neurodegenerative diseases
Query!
Metabolic and Endocrine
0
0
0
0
Query!
Metabolic disorders
Query!
Human Genetics and Inherited Disorders
0
0
0
0
Query!
Other human genetics and inherited disorders
Query!
Metabolic and Endocrine
0
0
0
0
Query!
Other metabolic disorders
Query!
Intervention/exposure
Study type
Interventional(has expanded access)
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Inotersen
Treatment: Drugs - Placebo
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
Treatment: Drugs: Inotersen
Treatment: Drugs: Placebo
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Baseline and Week 66
Query!
Primary outcome [2]
0
0
Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Baseline and Week 66
Query!
Secondary outcome [1]
0
0
Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Baseline and Week 66
Query!
Secondary outcome [2]
0
0
Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Baseline and Week 66
Query!
Secondary outcome [3]
0
0
Change From Baseline In Modified Body Mass Index (mBMI) at Week 65
Query!
Assessment method [3]
0
0
The mBMI is the BMI multiplied by the serum albumin g/L
Query!
Timepoint [3]
0
0
Baseline and Week 65
Query!
Secondary outcome [4]
0
0
Change From Baseline In Body Mass Index (BMI) at Week 65
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
Baseline and Week 65
Query!
Secondary outcome [5]
0
0
Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66
Query!
Assessment method [5]
0
0
The NIS score is a measure of neurologic impairment. The NIS Score has a range of 0 to 244 and a higher NIS score indicates lower function.
Query!
Timepoint [5]
0
0
Baseline and Week 66
Query!
Secondary outcome [6]
0
0
Change From Baseline in Modified +7 at Week 66
Query!
Assessment method [6]
0
0
The Modified +7 score is a version of the NIS score that is a measure of neurologic impairment. The Modified +7 Score has a range of -22.32 to 102.32 and a higher NIS score indicates lower function.
Query!
Timepoint [6]
0
0
Baseline and Week 66
Query!
Secondary outcome [7]
0
0
Change From Baseline in NIS+7 at Week 66
Query!
Assessment method [7]
0
0
The NIS+7 score is a version of the NIS score that is a measure of neurologic impairment. The NIS+7 Score has a range of -26.04 to 270.04 and a higher NIS score indicates lower function.
Query!
Timepoint [7]
0
0
Baseline and Week 66
Query!
Secondary outcome [8]
0
0
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set
Query!
Assessment method [8]
0
0
GLS by ECHO is a measure of cardiac systolic function
Query!
Timepoint [8]
0
0
Baseline and Week 65
Query!
Secondary outcome [9]
0
0
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup
Query!
Assessment method [9]
0
0
GLS by ECHO is a measure of cardiac systolic function
Query!
Timepoint [9]
0
0
Baseline and Week 65
Query!
Secondary outcome [10]
0
0
Change From Baseline in Transthyretin (TTR) Level at Week 65
Query!
Assessment method [10]
0
0
Query!
Timepoint [10]
0
0
Baseline and Week 65
Query!
Secondary outcome [11]
0
0
Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65
Query!
Assessment method [11]
0
0
Query!
Timepoint [11]
0
0
Baseline and Week 65
Query!
Secondary outcome [12]
0
0
Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65
Query!
Assessment method [12]
0
0
Query!
Timepoint [12]
0
0
Week 65
Query!
Secondary outcome [13]
0
0
Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65
Query!
Assessment method [13]
0
0
Query!
Timepoint [13]
0
0
Week 65
Query!
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
Query!
Assessment method [14]
0
0
Query!
Timepoint [14]
0
0
Week 65
Query!
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
Query!
Assessment method [15]
0
0
Query!
Timepoint [15]
0
0
Week 65
Query!
Secondary outcome [16]
0
0
Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65
Query!
Assessment method [16]
0
0
Query!
Timepoint [16]
0
0
Week 65
Query!
Secondary outcome [17]
0
0
Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65
Query!
Assessment method [17]
0
0
Query!
Timepoint [17]
0
0
Week 65
Query!
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
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
82
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
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
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2/Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
15/03/2013
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
7/11/2017
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
173
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Indiana
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Maryland
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Massachusetts
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Minnesota
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
New York
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Oregon
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Pennsylvania
Query!
Country [9]
0
0
Argentina
Query!
State/province [9]
0
0
Buenos Aires
Query!
Country [10]
0
0
Brazil
Query!
State/province [10]
0
0
Rio de Janeiro
Query!
Country [11]
0
0
Brazil
Query!
State/province [11]
0
0
Sao Paulo
Query!
Country [12]
0
0
France
Query!
State/province [12]
0
0
Creteil
Query!
Country [13]
0
0
France
Query!
State/province [13]
0
0
Le Kremlin Bicetre
Query!
Country [14]
0
0
Germany
Query!
State/province [14]
0
0
Munster
Query!
Country [15]
0
0
Italy
Query!
State/province [15]
0
0
Sicily
Query!
Country [16]
0
0
Italy
Query!
State/province [16]
0
0
Pavia
Query!
Country [17]
0
0
New Zealand
Query!
State/province [17]
0
0
Auckland
Query!
Country [18]
0
0
Portugal
Query!
State/province [18]
0
0
Lisbon
Query!
Country [19]
0
0
Portugal
Query!
State/province [19]
0
0
Porto
Query!
Country [20]
0
0
Spain
Query!
State/province [20]
0
0
Barcelona
Query!
Country [21]
0
0
United Kingdom
Query!
State/province [21]
0
0
London
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Ionis Pharmaceuticals, Inc.
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
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).
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01737398
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01737398
Download to PDF