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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/NCT03860935




Registration number
NCT03860935
Ethics application status
Date submitted
27/02/2019
Date registered
4/03/2019
Date last updated
10/07/2023

Titles & IDs
Public title
Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of AG10 in Subjects With Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTRibute-CM Trial)
Secondary ID [1] 0 0
2018-004280-32
Secondary ID [2] 0 0
AG10-301
Universal Trial Number (UTN)
Trial acronym
ATTRibute-CM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyloidosis 0 0
Amyloid Cardiomyopathy 0 0
Transthyretin Amyloidosis 0 0
Cardiomyopathies 0 0
Heart Diseases 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular 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 - acoramidis
Treatment: Drugs - Placebo Oral Tablet

Experimental: acoramidis HCl 800 mg - Subjects will receive acoramidis HCl 800 mg twice daily. 6MWT primary outcome will be assessed at the end of 12 months. The hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP levels, and change from baseline in distance walked on the 6MWT will be assessed after 30 months of treatment.

Placebo Comparator: Placebo - Subjects will receive placebo to match twice daily. 6MWT primary outcome will be assessed at the end of 12 months. The hierarchical combination of All-Cause mortality, cumulative frequency of cardiovascular-related hospitalizations, change from baseline in NT-proBNP levels, and change from baseline in distance walked on the 6MWT will be assessed after 30 months of treatment.


Treatment: Drugs: acoramidis
TTR stabilizer administered orally twice daily (BID)

Treatment: Drugs: Placebo Oral Tablet
Non-active control administered orally twice daily (BID)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
6-Minute Walk Test (6MWT) through Month 12
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
A hierarchical combination of all-cause mortality, cumulative frequency of cardiovascular-related hospitalization, change from baseline in NT-proBNP, and change from baseline in 6MWT over a 30-month fixed treatment duration
Timepoint [2] 0 0
30 months
Secondary outcome [1] 0 0
Evaluate effects of acoramidis on quality of life (QoL) through Month 12
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Evaluate 6-Minute Walk Test (6MWT) through Month 30
Timepoint [2] 0 0
30 months
Secondary outcome [3] 0 0
Evaluate effects of acoramidis on quality of life (QoL) through Month 30
Timepoint [3] 0 0
30 months
Secondary outcome [4] 0 0
Assess PD effects of circulating prealbumin by in vivo biomarker stabilization through Month 30
Timepoint [4] 0 0
30 months
Secondary outcome [5] 0 0
Assess all-cause mortality
Timepoint [5] 0 0
30 months
Secondary outcome [6] 0 0
Assess safety and tolerability through Month 12
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
PD assessments of TTR stabilization through Month 12
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Efficacy by individual components and hierarchical combinations through Month 30
Timepoint [8] 0 0
30 months
Secondary outcome [9] 0 0
Efficacy of acoramidis in reducing CV mortality
Timepoint [9] 0 0
30 months
Secondary outcome [10] 0 0
Incidence of treatment-emergent events
Timepoint [10] 0 0
30 months

Eligibility
Key inclusion criteria
- Have an established diagnosis of ATTR-CM with either wild-type TTR or variant TTR
genotype

- Have a history of heart failure evidenced by at least one prior hospitalization for
heart failure or clinical evidence of heart failure without prior heart failure
hospitalization manifested by signs or symptoms of volume overload or elevated
intracardiac pressures or heart failure symptoms that required or require ongoing
treatment with a diuretic.

- New York Heart Association (NYHA) Class I-III symptoms due to ATTR cardiomyopathy.

- On stable doses of cardiovascular medical therapy

- Completed =150 m on the 6MWT on 2 tests that are within 15% of total distance walked
prior to randomization

- Biomarkers of myocardial wall stress, NT-proBNP level =300 pg/mL at screening

- Have left ventricular wall (interventricular septum or left ventricular posterior
wall) thickness =12 mm
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Had acute myocardial infarction, acute coronary syndrome or coronary
revascularization, or experienced stroke or transient ischemic attack within 90 days
prior to screening

- Has hemodynamic instability

- Likely to undergo heart transplantation within a year of screening

- Confirmed diagnosis of primary (light chain) amyloidosis

- Biomarkers of myocardial wall stress, NT-proBNP level =8500 pg/mL at screening

- Measure of kidney function, eGFR by MDRD formula <15 mL/min/1.73 m2

- Current treatment with marketed drug products and other investigational agents for the
treatment of ATTR-CM

- Current treatment with calcium channel blockers with conduction system effects (e.g.
verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed.
The use of digitalis will only be allowed if required for management of atrial
fibrillation with rapid ventricular response

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 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
19/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/05/2023
Sample size
Target
Accrual to date
Final
632
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [5] 0 0
Saint Vincent's Hospital Sydney - Sydney
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Box Hill
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- Hobart
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- Murdoch
Recruitment postcode(s) [5] 0 0
2010 - Sydney
Recruitment postcode(s) [6] 0 0
- Woolloongabba
Recruitment outside Australia
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California
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Colorado
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Connecticut
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District of Columbia
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Utah
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Washington
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Roma
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eidos Therapeutics, a BridgeBio company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Phase 3 efficacy and safety study to evaluate acoramidis (AG10) HCl 800 mg administered
orally twice a day compared to placebo in subjects with symptomatic Transthyretin Amyloid
Cardiomyopathy (ATTR-CM).
Trial website
https://clinicaltrials.gov/ct2/show/NCT03860935
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