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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04136171




Registration number
NCT04136171
Ethics application status
Date submitted
21/10/2019
Date registered
23/10/2019

Titles & IDs
Public title
CARDIO-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 Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Scientific title
A Phase 3 Global, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ION-682884 in Patients With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
Secondary ID [1] 0 0
2019-002835-27
Secondary ID [2] 0 0
ION-682884-CS2
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM) 0 0
Condition category
Condition code
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 - Placebo

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

Placebo comparator: Placebo - Eplontersen-matching placebo by subcutaneous injection once every 4 weeks


Treatment: Drugs: Eplontersen
Eplontersen by subcutaneous injection

Treatment: Drugs: Placebo
Eplontersen-matching placebo by subcutaneous injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite Outcome of Cardiovascular (CV) Mortality and Recurrent CV Clinical Events up to Week 140
Assessment method [1] 0 0
Timepoint [1] 0 0
Baseline up to Week 140
Secondary outcome [1] 0 0
Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 121
Assessment method [1] 0 0
The 6MWT is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWT provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions.
Timepoint [1] 0 0
Baseline to Week 121
Secondary outcome [2] 0 0
Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Week 121
Assessment method [2] 0 0
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item self-administered questionnaire developed to independently measure the participant's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life (QOL) within a 2-week recall period. The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best, with a higher score equaling a better score.
Timepoint [2] 0 0
Baseline to Week 121
Secondary outcome [3] 0 0
CV Clinical Events up to Week 140
Assessment method [3] 0 0
Timepoint [3] 0 0
Baseline up to Week 140
Secondary outcome [4] 0 0
CV Mortality up to Week 140
Assessment method [4] 0 0
Timepoint [4] 0 0
Baseline up to Week 140
Secondary outcome [5] 0 0
All-Cause Mortality up to Week 140
Assessment method [5] 0 0
Timepoint [5] 0 0
Baseline up to Week 140

Eligibility
Key inclusion criteria
* Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent. If engaged in sexual relations of child-bearing potential, agree to use 1 highly effective contraceptive method
* Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method
* Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99m Tc-pyrophosphate [PYP-Tc], or 99m Tc-hydroxymethylene-diphosphonate [HMDP-Tc]) with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio, centrally confirmed
* End-diastolic interventricular septum thickness of > 12 millimeters (mm) on Screening echocardiogram
* New York Heart Association (NYHA) class I-III
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening
* Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease
* Monoclonal gammopathy of undetermined significance (MGUS) and/or alterations in immunoglobulin free light chain (FLC) ratio unless fat, bone marrow, or heart biopsy confirming the absence of light chain and the presence of TTR protein by mass spectrometry or immunoelectron microscopy. For participants with chronic kidney disease (CKD) and without presence of monoclonal protein in blood and urine, the acceptable FLC ratio is 0.26-2.25. Results different from that may be discussed with local hematologist, Investigator and Medical Monitor if the risks associated with the biopsy outweigh the benefits
* Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated liver transplant or LVAD within 1 year after randomization
* Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or other oligonucleotide or ribonucleic acid (RNA) therapeutic (including small interfering ribonucleic acid [siRNA]; does not apply to COVID-19 mitochondrial [mRNA] vaccinations)
* Current treatment with diflunisal, doxycycline, with or without ursodeoxycholic acid, and/or non-dihydropyridine calcium-channel blocker (e.g., verapamil, diltiazem). Participants receiving any of these agents must respect a wash-out period of 14 days before randomization.

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2026
Actual
Sample size
Target
Accrual to date
Final
1438
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,West AustraliaWA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
The Westmead Institute for Medical Research - Westmead
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Advara Heartcare - Leabrook
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [7] 0 0
Advara HeartCare Murdoch - Murdoch
Recruitment hospital [8] 0 0
GenesisCare Murdoch - Murdoch
Recruitment hospital [9] 0 0
Advara HeartCare - Joondalup
Recruitment hospital [10] 0 0
GenesisCare Joondalup - Joondalup
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
NSW 2145 - Westmead
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5068 - Leabrook
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
Recruitment postcode(s) [8] 0 0
6027 - Joondalup
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
California
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Colorado
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District of Columbia
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United States of America
State/province [5] 0 0
Florida
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Georgia
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Illinois
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Indiana
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Kansas
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Missouri
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Liverpool
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London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

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

Data sharing statement


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/NCT04136171