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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04136184


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04136184
Ethics application status
Date submitted
21/10/2019
Date registered
23/10/2019

Titles & IDs
Public title
NEURO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
Scientific title
A Phase 3 Global, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of ION-682884 in Patients With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
Secondary ID [1] 0 0
2019-001698-10
Secondary ID [2] 0 0
ION-682884-CS3
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hereditary Transthyretin-Mediated Amyloid Polyneuropathy 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
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eplontersen
Treatment: Drugs - Inotersen

Experimental: Eplontersen - Eplontersen by subcutaneous injection once every 4 weeks.

Active comparator: Inotersen - Inotersen by subcutaneous injection once weekly through week 34. Participants will then convert to Eplontersen administered subcutaneously once every 4 weeks until the end of study.


Treatment: Drugs: Eplontersen
Eplontersen by subcutaneous injection

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

Outcomes
Primary outcome [1] 0 0
Change from baseline in mNIS+7 at Week 66
Timepoint [1] 0 0
Baseline, 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, Week 66
Primary outcome [3] 0 0
Percent change from baseline in serum TTR concentration at Week 66
Timepoint [3] 0 0
Baseline, Week 66
Primary outcome [4] 0 0
Percent change from baseline in serum transthyretin (TTR) concentration at Week 35
Timepoint [4] 0 0
Baseline, Week 35
Primary outcome [5] 0 0
Change from baseline in modified neuropathy impairment score plus 7 (mNIS+7) at Week 35
Timepoint [5] 0 0
Baseline, Week 35
Secondary outcome [1] 0 0
Change from baseline in Norfolk QOL-DN at Week 35
Timepoint [1] 0 0
Baseline, Week 35
Secondary outcome [2] 0 0
Change from baseline in Neuropathy Symptom and Change (NSC) score at Weeks 35 and 66
Timepoint [2] 0 0
Baseline, Week 35, Week 66
Secondary outcome [3] 0 0
Change from baseline in the Physical Component Summary (PCS) score of the 36-Item Short Form Survey (SF-36) at Week 65
Timepoint [3] 0 0
Baseline, Week 65
Secondary outcome [4] 0 0
Change from baseline in Polyneuropathy Disability (PND) score at Week 65
Timepoint [4] 0 0
Baseline, Week 65
Secondary outcome [5] 0 0
Change from baseline in modified body mass index (mBMI) at Week 65
Timepoint [5] 0 0
Baseline, Week 65

Eligibility
Key inclusion criteria
1. Aged 18 to 82 years at the time of informed consent
2. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent
3. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method
4. Diagnosis of hereditary transthyretin-mediated polyneuropathy as defined by meeting all 3 of the following:

* Stage 1 or Stage 2 Familial Amyloid Polyneuropathy (FAP) or Coutinho Stage
* Documented genetic mutation in the TTR gene
* Symptoms and signs consistent with neuropathy associated with transthyretin amyloidosis, including NIS = 10 and = 130
Minimum age
18 Years
Maximum age
82 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to abnormal safety labs
2. Karnofsky performance status = 50
3. Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes
4. Prior liver transplant or anticipated liver transplant within 1-yr of Screening
5. New York Heart Association (NYHA) functional classification of = 3
6. Acute coronary syndrome within 6 months of screening or major surgery within 3 months of Screening
7. Other types of amyloidosis
8. Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study
9. Current treatment with any approved drug for hereditary TTR amyloidosis such as Vyndaqel® / Vyndamax™ (tafamidis), Tegsedi™ (inotersen), Onpattro™ (patisiran), off-label use of diflunisal or doxycycline, and tauroursodeoxycholic acid (TUDCA). If previously treated with Vyndaqel® / Vyndamax™, diflunisal or doxycycline, and TUDCA, must have discontinued treatment for at least 2 weeks prior to Study Day 1
10. Previous treatment with Tegsedi™ (Inotersen) or Onpattro™ (patisiran), or other oligonucleotide or RNA therapeutic (including siRNA)

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
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
15/01/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/07/2023
Sample size
Target
Accrual to date
Final
168
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Brazil
State/province [14] 0 0
Parana
Country [15] 0 0
Brazil
State/province [15] 0 0
Paraná
Country [16] 0 0
Brazil
State/province [16] 0 0
Campinas
Country [17] 0 0
Brazil
State/province [17] 0 0
Ribeirão Preto
Country [18] 0 0
Brazil
State/province [18] 0 0
Rio De Janeiro
Country [19] 0 0
Brazil
State/province [19] 0 0
São Paulo
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Cyprus
State/province [21] 0 0
Egkomi
Country [22] 0 0
France
State/province [22] 0 0
Haute-Garonne
Country [23] 0 0
France
State/province [23] 0 0
Ile-De-France
Country [24] 0 0
France
State/province [24] 0 0
Marseille
Country [25] 0 0
Germany
State/province [25] 0 0
Bayern
Country [26] 0 0
Germany
State/province [26] 0 0
Heidelberg
Country [27] 0 0
Greece
State/province [27] 0 0
Crete
Country [28] 0 0
Italy
State/province [28] 0 0
Messina
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Pavia
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
New Zealand
State/province [32] 0 0
Auckland
Country [33] 0 0
Portugal
State/province [33] 0 0
Lisbon
Country [34] 0 0
Portugal
State/province [34] 0 0
Porto
Country [35] 0 0
Spain
State/province [35] 0 0
Illes Balears
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
Sweden
State/province [37] 0 0
Umeå
Country [38] 0 0
Taiwan
State/province [38] 0 0
Guishan District
Country [39] 0 0
Taiwan
State/province [39] 0 0
Taichung
Country [40] 0 0
Taiwan
State/province [40] 0 0
Taipei
Country [41] 0 0
Turkey
State/province [41] 0 0
Istanbul

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04136184

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
Ionis Pharmaceuticals
Primary sponsor address
2855 Gazelle Court
Carlsbad, CA 92010
Primary sponsor country
United States of America
Other collaborator category [1] 14
Commercial sector/Industry
Name [1] 14
Akcea Therapeutics
Address [1] 14
Country [1] 14
United States of America
Ethics approval
Ethics application status
Approved
 
Public notes

Contacts
Principal investigator
Title 109 0
Name 109 0
Address 109 0
Country 109 0
Phone 109 0
Fax 109 0
Email 109 0
Contact person for public queries
Title 110 0
Name 110 0
Address 110 0
Country 110 0
Phone 110 0
Fax 110 0
Email 110 0
[email protected]
Contact person for scientific queries
Title 111 0
Name 111 0
Address 111 0
Country 111 0
Phone 111 0
Fax 111 0
Email 111 0
[email protected]