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

Phase 3CompletedNCT04622046

Alexion Pharmaceuticals, Inc.25 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Symptomatic Transthyretin Amyloid Cardiomyopathy

Interventions

ALXN2060DRUG

ALXN2060 tablets will be administered twice daily at a dose of 800 milligrams.

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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.

Locations (11)

Research Site

Bunkyō City, Japan

Research Site

Fukuoka, Japan

Research Site

Kumamoto, Japan

Research Site

Kurume-shi, Japan

Outcomes

Primary Outcomes

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.

Time frame: 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).

Time frame: 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.

Time frame: 30 months

Secondary Outcomes

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.

Data from ClinicalTrials.gov

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