A Phase 3 Study of ALXN2060 in Japanese Participants With Symptomatic ATTR-CM

A Phase 3, Prospective, Multicenter, Open Label, 2-Part Study of the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of ALXN2060 in Japanese Participants With Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

This prospective study is designed to evaluate the efficacy, safety, and tolerability of ALXN2060 (also known as AG10), as well as to establish its pharmacokinetic and pharmacodynamic profile in Japanese participants with symptomatic ATTR-CM administered on a background of stable heart failure therapy.

Study Overview

• Status: Completed
• Conditions: Symptomatic Transthyretin Amyloid Cardiomyopathy
• Intervention / Treatment: Drug: ALXN2060

Detailed Description

Participants will receive ALXN2060 for 12 months (Part A). Following the last visit (Month 12) of Part A, participants will continue the study in Part B, which will last for an additional 18 months (30 months from Day 1), during which all participants will continue to receive oral treatment with ALXN2060. Following completion of Month 30 assessments in Part B, participants will be offered the opportunity to continue to receive ALXN2060 in the Extension Period, which will last until ALXN2060 is approved in Japan or for up to 24 additional months, whichever occurs first.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Bunkyō City, Japan, 113-8431
    • Research Site
  • Fukuoka, Japan, 812-8582
    • Research Site
  • Kumamoto, Japan, 860-8556
    • Research Site
  • Kurume-shi, Japan, 830-0011
    • Research Site
  • Matsumoto-shi, Japan, 390-8621
    • Research Site
  • Nagoya, Japan, 466-8560
    • Research Site
  • Nankoku-shi, Japan, 783-8505
    • Research Site
  • Sagamihara-shi, Japan, 252-0375
    • Research Site
  • Sapporo, Japan, 060-8543
    • Research Site
  • Shinjuku-ku, Japan, 160-8582
    • Research Site
  • Suita-shi, Japan, 564-8565
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 86 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Established diagnosis of ATTR-CM with either wild-type TTR or a variant TTR genotype.
2. History of heart failure evidenced by at least 1 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 pressures or heart failure symptoms that required or requires ongoing treatment with a diuretic.
3. New York Heart Association Class I-III symptoms due to ATTR-CM.
4. On stable doses of cardiovascular medical therapy.
5. Completed ≥ 150 meters on the 6MWT on 2 tests prior to Day 1.
6. Left ventricular (LV) wall (interventricular septum or LV posterior wall) thickness ≥ 12 millimeters.
7. Biomarkers of myocardial wall stress: N-terminal pro-brain-type natriuretic pep (NT-proBNP) level ≥ 300 picograms/milliliter (pg/mL).

Exclusion Criteria:

1. Acute myocardial infarction, acute coronary syndrome or coronary revascularization, or experienced stroke or transient ischemic attack within 90 days prior to screening.
2. Hemodynamic instability at screening.
3. Likely to undergo heart transplantation within a year of screening.
4. Current treatment with marketed drug products and other investigational agents for the treatment of ATTR-CM.
5. Current treatment with calcium channel blockers with conduction system effects (for example, verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed.
6. Confirmed diagnosis of light-chain (AL) amyloidosis.
7. Biomarkers of myocardial wall stress: NT-ProBNP ≥ 8,500 pg/mL.
8. Measure of kidney function, estimated glomerular filtration rate by Modification of Diet in Renal Disease formula < 30 mL/minute/1.73 meters squared.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALXN2060; Participants will receive ALXN2060.	Drug: ALXN2060; ALXN2060 tablets will be administered twice daily at a dose of 800 milligrams.; Other Names: AG10; Acoramidis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Change From Baseline To Month 12 Of Treatment In Distance Walked During The Six-minute Walk Test (6MWT)	The 6MWT measures how far a participant can walk in 6 minutes. Change from baseline was calculated as the difference between the distance walked during the 6MWT at 12 months and the distance walked during the 6MWT at baseline. To determine the baseline, at least 2 6MWTs were conducted > 24 hours to ≤ 3 weeks apart prior to the first dose of ALXN2060. The baseline 6MWT is the average of the total distance walked by participants for the 2 qualifying 6MWTs that met all the protocol-defined criteria. Least squares mean change from baseline data were adjusted for baseline measures and visits.	Baseline, Month 12
Parts A and B: Number of Cardiovascular (CV)-Related Hospitalizations Over A 30-month Period	CV-related hospitalization was defined as the mean number of CV-related hospitalizations per participant per year over a 30-month period. CV-related hospitalizations were also reported as adverse events and were reviewed and adjudicated by an independent Clinical Events Committee (CEC).	30 months
All-cause Mortality (ACM) Over A 30-month Period	ACM was assessed as time from the date of first initiation of study treatment to the date of death during a 30-month period, and was analyzed using Kaplan-Meier analysis. Data are reported for the number of participants with ACM over the 30-month period.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and B: Change From Baseline In Distance Walked During The 6MWT	The 6MWT measures how far a participant can walk in 6 minutes. Change from baseline was calculated as the difference between the distance walked during the 6MWT at specified timepoints and the distance walked during the 6MWT at baseline. To determine the baseline, at least 2 6MWTs were conducted > 24 hours to ≤ 3 weeks apart prior to the first dose of ALXN2060. The baseline 6MWT is the average of the total distance walked by participants for the 2 qualifying 6MWTs that met all the protocol-defined criteria. Least squares mean change from baseline data were adjusted for baseline measures and visits.	Baseline, Months 6, 9, 18, 24 and 30
Parts A and B: Change From Baseline In The Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)	The KCCQ is a 23-item questionnaire developed to measure health status and health-related quality of life in participants with heart failure. Items include heart failure symptoms, impact on physical and social functions, and how their heart failure impacts their quality of life. The overall summary score ranged from 0-100, with higher scores indicating better health status. Data presented are for change from baseline to specified timepoints. Least squares mean change from baseline data were adjusted for baseline measures and visits.	Baseline, Months 6, 9, 12, 18, 24 and 30
Parts A and B: Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation	A treatment-emergent AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention that occurred after first dose. A treatment-emergent SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or was a congenital anomaly/birth defect that occurred after first dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to Month 30
Parts A and B: Change From Baseline In Serum Transthyretin (TTR) Concentration	Least squares mean change from baseline derived from with visits and baseline serum TTR as a covariate. Other covariates were included as needed.	Baseline, pre-dose on Days 14, 28 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30
Parts A and B: Change From Baseline In TTR Stabilization	TTR stabilization was measured using fluorescent probe exclusion (FPE). Data presented are for change from baseline in FPE percentage stabilization.	Baseline, Pre-dose Days 14, 28 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: Eidos Therapeutics, a BridgeBio, Inc. Company

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): November 8, 2023
• Study Completion (Actual): August 21, 2025

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Metabolic Diseases; Proteostasis Deficiencies; Cardiomyopathies; Amyloidosis; attruby
• Other Study ID Numbers: ALXN2060-TAC-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No