Clinical trial NCT04622046: A Phase 3 Study of ALXN2060 in Japanese Participants With Symptomatic ATTR-CM
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Symptomatic Transthyretin Amyloid Cardiomyopathy
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Eidos Therapeutics, a BridgeBio, Inc. Company
First posted: 2020-11-09
Enrollment: 25
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Part A: Change From Baseline To Month 12 Of Treatment In Distance Walked During The Six-minute Walk Test (6MWT)
timeFrame: Baseline, Month 12
measure: Parts A and B: Number of Cardiovascular (CV)-Related Hospitalizations Over A 30-month Period
timeFrame: 30 months
measure: All-cause Mortality (ACM) Over A 30-month Period
timeFrame: 30 months
Secondary outcomes:
measure: Parts A and B: Change From Baseline In Distance Walked During The 6MWT
timeFrame: Baseline, Months 6, 9, 18, 24 and 30
measure: Parts A and B: Change From Baseline In The Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)
timeFrame: Baseline, Months 6, 9, 12, 18, 24 and 30
measure: Parts A and B: Number of Participants With Treatment-emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
timeFrame: Up to Month 30
measure: Parts A and B: Change From Baseline In Serum Transthyretin (TTR) Concentration
timeFrame: Baseline, pre-dose on Days 14, 28 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30
measure: Parts A and B: Change From Baseline In TTR Stabilization
timeFrame: Baseline, Pre-dose Days 14, 28 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30
Other outcomes:
Locations:
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Matsumoto-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nankoku-shi
country: Japan
facility: Research Site
city: Sagamihara-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
Study officials:
References: