NCT03860935: ATTRibute-CM

Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy

Completed Phase 3 Results posted Last updated 27 June 2024

What this trial tests

Phase 3 trial testing acoramidis in Amyloidosis in 632 participants. Completed in 11 May 2023.

Timeline

19 March 2019

Primary endpoint
11 May 2023

11 May 2023

Quick facts

Lead sponsor	Eidos Therapeutics, a BridgeBio company
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	632
Start date	19 March 2019
Primary completion	11 May 2023
Estimated completion	11 May 2023
Sites	104 locations across Denmark, Italy, Netherlands, New Zealand, Greece, Belgium, Ireland, United Kingdom

Drugs / interventions tested

• acoramidis (ACORAMIDIS) — full drug profile →
• Placebo Oral Tablet — full drug profile →

Conditions studied

• Amyloidosis — all drugs for Amyloidosis →
• Amyloid Cardiomyopathy — all drugs for Amyloid Cardiomyopathy →
• Transthyretin Amyloidosis — all drugs for Transthyretin Amyloidosis →
• Cardiomyopathies — all drugs for Cardiomyopathies →

Sponsor

Eidos Therapeutics, a BridgeBio company — full company profile →

Who can join

Adults 18 to 90, any sex, with Amyloidosis or Amyloid Cardiomyopathy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

A Hierarchical Combination of All-Cause Mortality, Cumulative Frequency of CV-related Hospitalization, Change From Baseline in NT-proBNP and Change From Baseline in 6MWT at the Last Available Visit Where Both Subjects Had Non-missing Assessments. Primary · Baseline up to Month 30

The endpoint was analyzed using Finkelstein-Schoenfeld method. The method combines all-cause mortality, cumulative frequency of CV-related hospitalizations, change from baseline in NT-proBNP and change from baseline in 6MWT in a hierarchical fashion. The method compares every participant with every other participant within strata, assigning a +1 to the "better" participant and a -1 to the "worse" participant and 0 if they are "tied". Participants who had heart transplantation or implantation of a cardiac mechanical assist device were handled in the same manner as death. 'Win' represents a part

Group	Value	95% CI
Acoramidis HCl 800 mg	63.7
Placebo	35.9

Change From Baseline to Month 30 in the Distance Walked During the 6 Minute Walk Test (6MWT) Secondary · Month 30

6MWT measures the total distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.

Group	Value	95% CI
Acoramidis HCl 800 mg	-64.65	± 5.508
Placebo	-104.29	± 7.772

Change From Baseline to Month 30 of the Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) Secondary · Month 30

KCCQ is a 23-item participant-completed questionnaire that assesses health status and health-related quality of life in participants with heart failure. Eight domain scores were calculated for the KCCQ: Physical limitation, Social limitation, Quality of life, Self-efficacy, Symptom stability, Symptom frequency, Symptom burden, and Total symptoms (calculated as the mean of Symptom frequency and Symptom burden scores). The summary score of Overall Summary (calculated as mean of Physical limitation, Social limitation, Total symptoms, and Quality of life scores) was calculated. Domain and summary

Group	Value	95% CI
Acoramidis HCl 800 mg	-11.48	± 1.181
Placebo	-21.42	± 1.651

Change From Baseline to Month 30 in Serum TTR (Prealbumin) Level Secondary · Month 30

Serum TTR (Prealbumin) is an in vivo biomarker of stabilization.

Group	Value	95% CI
Acoramidis HCl 800 mg	5.78	± 0.391
Placebo	-1.32	± 0.541

All-cause Mortality by Month 30, Including Death Due to Any Cause, Heart Transplant or Cardiac Mechanical Assist Device (CMAD) Secondary · Baseline up to Month 30

Number of deaths due to any cause was analyzed. Participants who had heart transplantation or implantation of a CMAD were handled in the same manner as death.

Group	Value	95% CI
Acoramidis HCl 800 mg	79
Placebo	52

Adverse events — posted to ClinicalTrials.gov

Time frame: In Study AG10-301 participants, treatment emergent adverse events (TEAEs) are defined as (a) events with onset after the first dose of study drug, or (b) if the event was present before the first dose of study drug, but increased in severity after the first dose of study drug, and (c) with onset date or severity increase date <= 30 days after the last dose of study drug (through AG10-301 Study completion, 30 months) or until the first dose in open label extension Study AG10-304.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Acoramidis HCl 800 mg

Serious: 230/421 (55%)

Deaths: 84/421

Placebo

Serious: 137/211 (65%)

Deaths: 55/211

Serious adverse events (313 terms)

Reaction	System	Acoramidis HCl 800 mg	Placebo
Cardiac failure	Cardiac disorders	—	—
Cardiac failure acute	Cardiac disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Pneumonia	Infections and infestations	—	—
Bradycardia	Cardiac disorders	—	—
COVID-19	Infections and infestations	—	—
Atrioventricular block complete	Cardiac disorders	—	—
COVID-19 pneumonia	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Cellulitis	Infections and infestations	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Ventricular tachycardia	Cardiac disorders	—	—
Cardiac failure chronic	Cardiac disorders	—	—
Inguinal hernia	Gastrointestinal disorders	—	—
Syncope	Nervous system disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—
Presyncope	Nervous system disorders	—	—
Hypervolaemia	Metabolism and nutrition disorders	—	—
Cardiac arrest	Cardiac disorders	—	—
Sepsis	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—

Other adverse events (41 terms — click to expand)

Reaction	System	Acoramidis HCl 800 mg	Placebo
COVID-19	Infections and infestations	—	—
Cardiac failure	Cardiac disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Atrial fibrillation	Cardiac disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Gout	Metabolism and nutrition disorders	—	—
Dizziness	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Renal impairment	Renal and urinary disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Oedema peripheral	General disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Hypotension	Vascular disorders	—	—
Blood creatinine increased	Investigations	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Hypervolaemia	Metabolism and nutrition disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Asthenia	General disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Insomnia	Psychiatric disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Haematuria	Renal and urinary disorders	—	—
Weight decreased	Investigations	—	—
Syncope	Nervous system disorders	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Peripheral swelling	General disorders	—	—
Ventricular tachycardia	Cardiac disorders	—	—

Most-reported serious reactions: Cardiac failure, Cardiac failure acute, Acute kidney injury, Atrial fibrillation, Fall, Pneumonia, Bradycardia, COVID-19.

Data from ClinicalTrials.gov NCT03860935 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy.
   Gillmore JD, Judge DP, Cappelli F, Fontana M, et al · · 2024 · cited 342× · PMID 38197816 · DOI 10.1056/nejmoa2305434
2. Transthyretin cardiac amyloidosis: an update on diagnosis and treatment.
   Yamamoto H, Yokochi T. · · 2019 · cited 131× · PMID 31553132 · DOI 10.1002/ehf2.12518
3. Pathophysiology and Therapeutic Approaches to Cardiac Amyloidosis.
   Griffin JM, Rosenblum H, Maurer MS. · · 2021 · cited 130× · PMID 33983835 · DOI 10.1161/circresaha.121.318187
4. Transthyretin cardiac amyloidosis.
   Porcari A, Fontana M, Gillmore JD. · · 2023 · cited 123× · PMID 35929637 · DOI 10.1093/cvr/cvac119
5. ATTR Amyloidosis: Current and Emerging Management Strategies: <i>JACC: CardioOncology</i> State-of-the-Art Review.
   Griffin JM, Rosenthal JL, Grodin JL, Maurer MS, et al · · 2021 · cited 110× · PMID 34729521 · DOI 10.1016/j.jaccao.2021.06.006
6. Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis.
   Carroll A, Dyck PJ, de Carvalho M, Kennerson M, et al · · 2022 · cited 79× · PMID 35256455 · DOI 10.1136/jnnp-2021-327909
7. Hereditary transthyretin amyloidosis overview.
   Manganelli F, Fabrizi GM, Luigetti M, Mandich P, et al · · 2022 · cited 78× · PMID 33188616 · DOI 10.1007/s10072-020-04889-2
8. World Heart Federation Consensus on Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM).
   Brito D, Albrecht FC, de Arenaza DP, Bart N, et al · · 2023 · cited 62× · PMID 37901600 · DOI 10.5334/gh.1262