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

• ClinicalTrials.gov Identifier: NCT04622046
• Recruitment Status: Active, not recruiting
• First Posted: November 9, 2020
• Last Update Posted: April 10, 2024
• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborator: Eidos Therapeutics, a BridgeBio company
• Information provided by (Responsible Party): Alexion Pharmaceuticals, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Symptomatic Transthyretin Amyloid Cardiomyopathy	Drug: ALXN2060	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: November 13, 2020
• Actual Primary Completion Date: November 8, 2023
• Estimated Study Completion Date: September 23, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline To Month 12 Of Treatment In Distance Walked During The Six-minute Walk Test (6MWT) [ Time Frame: Baseline, Month 12 ]
2. All-cause Mortality And Cardiovascular-related Hospitalization Over A 30-month Period [ Time Frame: Baseline through Month 30 ]

Secondary Outcome Measures :

1. Change From Baseline To Month 30 Of Treatment In Distance Walked During The 6MWT [ Time Frame: Baseline, Month 30 ]
2. Change From Baseline To Month 12 Of Treatment In The Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) [ Time Frame: Baseline, Month 12 ]
3. Change From Baseline To Month 30 Of Treatment In The KCCQ-OS [ Time Frame: Baseline, Month 30 ]
4. Incidence Of Treatment-emergent Serious Adverse Events (SAEs) And Adverse Events (AEs) [ Time Frame: Baseline through Month 12 ]
5. Incidence Of Treatment-emergent SAEs And AEs [ Time Frame: Baseline through Month 30 ]
6. Change From Baseline To Day 28 In Transthyretin (TTR) Stabilization [ Time Frame: Baseline, Day 28 ]
7. Change From Baseline To Month 30 In TTR Stabilization [ Time Frame: Baseline, Month 30 ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Japan

Research Site

Bunkyo-ku, Japan, 113-8431

Research Site

Fukuoka-shi, Japan, 812-8582

Research Site

Kumamoto-shi, Japan, 860-8556

Research Site

Kurume-shi, Japan, 830-0011

Research Site

Matsumoto-shi, Japan, 390-8621

Research Site

Nagoya-shi, Japan, 466-8560

Research Site

Nankoku-shi, Japan, 783-8505

Research Site

Sagamihara-shi, Japan, 252-0375

Research Site

Sapporo-shi, Japan, 060-8543

Research Site

Shinjuku-ku, Japan, 160-8582

Research Site

Suita-shi, Japan, 564-8565

Sponsors and Collaborators

Alexion Pharmaceuticals, Inc.

Eidos Therapeutics, a BridgeBio company

More Information

• Responsible Party: Alexion Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04622046
• Other Study ID Numbers: ALXN2060-TAC-302
• First Posted: November 9, 2020
• Last Update Posted: April 10, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Cardiomyopathies; Amyloidosis; Heart Diseases; Cardiovascular Diseases; Proteostasis Deficiencies; Metabolic Diseases