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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02175004




Registration number
NCT02175004
Ethics application status
Date submitted
12/06/2014
Date registered
26/06/2014
Date last updated
9/02/2023

Titles & IDs
Public title
Extension Study Assessing Long Term Safety and Efficacy of IONIS-TTR Rx in Familial Amyloid Polyneuropathy (FAP)
Scientific title
An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (FAP)
Secondary ID [1] 0 0
2013-004561-13
Secondary ID [2] 0 0
ISIS 420915-CS3
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
Treatment: Drugs - Inotersen

Experimental: Previous Placebo-Inotersen 300 mg - Participants received subcutaneous (SC) doses of 300 milligrams (mg) inotersen once weekly for up to 260 weeks. Participants who received inotersen-matching placebo in the previous study- ISIS 420915-CS2 (NCT01737398) were included in this group.

Experimental: Previous Inotersen-Inotersen 300 mg - Participants received SC doses of 300 mg inotersen once weekly for up to 260 weeks. Participants who received inotersen in the previous study- ISIS 420915-CS2 were included in this group.


Treatment: Drugs: Inotersen
Inotersen SC
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Related to Study Drug
Timepoint [1] 0 0
From first dose of study drug up to 3 months post treatment period of 260 weeks (Up to approximately 272 weeks)
Primary outcome [2] 0 0
Percentage of Participants With Change From Baseline in Vital Signs
Timepoint [2] 0 0
From first dose of study drug up to 3 months post treatment period of 260 weeks (Up to approximately 272 weeks)
Primary outcome [3] 0 0
Percentage of Participants With Change From Baseline in Weight
Timepoint [3] 0 0
From first dose of study drug up to 3 months post treatment period of 260 weeks (Up to approximately 272 weeks)
Primary outcome [4] 0 0
Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Test Values
Timepoint [4] 0 0
From first dose of study drug up to 3 months post treatment period of 260 weeks (Up to approximately 272 weeks)
Primary outcome [5] 0 0
Percentage of Participants With Change From Baseline in QT Interval Corrected Using Fridericia's Formula (QTcF) as Determined by Electrocardiogram (ECG)
Timepoint [5] 0 0
From first dose of study drug up to 3 months post treatment period of 260 weeks (Up to approximately 272 weeks)
Primary outcome [6] 0 0
Percentage of Participants Using Concomitant Medication for Nervous and Cardiovascular System Disorders
Timepoint [6] 0 0
From first dose of study drug up to 3 months post treatment period of 260 weeks (Up to approximately 272 weeks)
Primary outcome [7] 0 0
Percentage of Participants With Change From Baseline in Ophthalmic Examination as Assessed by Visual Acuity Changes
Timepoint [7] 0 0
From first dose of study drug up to 3 months post treatment period of 260 weeks (Up to approximately 272 weeks)
Primary outcome [8] 0 0
Percentage of Participants With Change From Baseline in Light Detection Ability Measured by Electroretinography
Timepoint [8] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156
Secondary outcome [1] 0 0
Change From Baseline in the Modified Neuropathy Impairment Score (mNIS)+7 Composite Score at Weeks 78 and 156
Timepoint [1] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156
Secondary outcome [2] 0 0
Change From Baseline in the mNIS +7 Component: Heart Rate to Deep Breathing Score at Weeks 78 and 156
Timepoint [2] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156
Secondary outcome [3] 0 0
Change From Baseline in the mNIS +7 Component: Nerve Conduction Score at Weeks 78 and 156
Timepoint [3] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156
Secondary outcome [4] 0 0
Change From Baseline in the mNIS +7 Component: Heat-Pain Sensory Score at Weeks 78 and 156
Timepoint [4] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156
Secondary outcome [5] 0 0
Change From Baseline in the mNIS +7 Component: Touch-Pressure Sensory Score at Weeks 78 and 156
Timepoint [5] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156
Secondary outcome [6] 0 0
Change From Baseline in the Neuropathy Impairment (NIS) Composite Score at Week 52 of Years 4 and 5
Timepoint [6] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Week 52 of Years 4 and 5
Secondary outcome [7] 0 0
Change From Baseline in the NIS Component: Cranial Nerves Score at Week 52 of Years 4 and 5
Timepoint [7] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Week 52 of Years 4 and 5
Secondary outcome [8] 0 0
Change From Baseline in the NIS Component: Muscle Weakness Score at Week 52 of Years 4 and 5
Timepoint [8] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Week 52 of Years 4 and 5
Secondary outcome [9] 0 0
Change From Baseline in the NIS Component: Reflexes Score at Week 52 of Years 4 and 5
Timepoint [9] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Week 52 of Years 4 and 5
Secondary outcome [10] 0 0
Change From Baseline in the NIS Component: Sensory Score at Week 52 of Years 4 and 5
Timepoint [10] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Week 52 of Years 4 and 5
Secondary outcome [11] 0 0
Change From Baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) Questionnaire Total Score at Weeks 78 and 156
Timepoint [11] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156 and at the end of each subsequent treatment year (Week 52 of Years 4 and 5)
Secondary outcome [12] 0 0
Change From Baseline in the Norfolk QoL-DN Physical Functioning/Large Fiber Neuropathy Domain Score
Timepoint [12] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156 and at the Week 52 of Year 4
Secondary outcome [13] 0 0
Change From Baseline in the Modified Body Mass Index (mBMI) at Weeks 78 and 156
Timepoint [13] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156
Secondary outcome [14] 0 0
Change From Baseline in the Body Mass Index (BMI) at Weeks 78 and 156
Timepoint [14] 0 0
Baseline, Weeks 78 and 156
Secondary outcome [15] 0 0
Percentage of Participants With Change From Baseline in the Polyneuropathy Disability (PND) Score
Timepoint [15] 0 0
Baseline, Weeks 78 and 156 and at the end of each subsequent treatment year (Week 52 of each year)
Secondary outcome [16] 0 0
Percent Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) in the Cardiomyopathy-ECHO (CM-ECHO) Set
Timepoint [16] 0 0
Baseline, Weeks 78 and 156
Secondary outcome [17] 0 0
Percent Change From Baseline in GLS by ECHO in the CS3 ECHO Subgroup
Timepoint [17] 0 0
Weeks 78 and 156
Secondary outcome [18] 0 0
Change From Baseline in Transthyretin (TTR) Level
Timepoint [18] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156
Secondary outcome [19] 0 0
Change From Baseline in Retinol Binding Protein 4 (RBP4) Level
Timepoint [19] 0 0
Baseline (Baseline is the Baseline of the Previous Study- Study CS2), Weeks 78 and 156, and at the end of each subsequent treatment year (Week 52 of Years 4 and 5)
Secondary outcome [20] 0 0
Ctrough: Trough Plasma Concentration of ISIS 420915
Timepoint [20] 0 0
Pre-dose on Days 1, 43, 85, 120, 176, 267, 358, 449, 540, 631, 722, 813, 904, 995, 1086, 1268; Days 1359 and 1450 of Year 4; Days 1632, 1723 and 1814 of Year 5

Eligibility
Key inclusion criteria
- Satisfactory completion of dosing & efficacy assessments in ISIS 420915-CS2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any new condition or worsening of existing condition that could make the patient
unsuitable for participation, or interfere with the patient participating in and/or
completing the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
26/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/01/2021
Sample size
Target
Accrual to date
Final
135
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
Portugal
State/province [17] 0 0
Lisbon
Country [18] 0 0
Portugal
State/province [18] 0 0
Porto
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
United Kingdom
State/province [20] 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
This study evaluates the safety and tolerability of extended dosing with IONIS-TTR Rx in
patients with Familial Amyloid Polyneuropathy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02175004
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

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