Dysautonomia International

A Phase III Study of AZD0780 on Major Adverse CV Events in Patients With a History of ASCVD Events or at High Risk for a First Event

Purpose

The purpose of this phase 3, randomized, placebo controlled, event-driven study is to assess the effect of AZD0780, an oral PCSK9 inhibitor, compared with placebo in reducing the risk of MACE-PLUS in patients with established ASCVD or at high risk for a first ASCVD event. The effect of AZD0780 vs placebo on the risk of MACE-PLUS will be evaluated from randomisation until the primary analysis censoring date (PACD). The Study Closure Visit will be scheduled to occur after the PACD and will be the final visit for each participant in the study.

Condition

Cardiovascular Disease

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Meets one of the following: 1. Participants with history of an ASCVD event: Participants ≥ 18 years of age at the time of signing the ICF with a history of MI or ischaemic stroke suspected to be due to atherosclerotic vascular disease ≥ 1 month prior to randomisation (presumed lacunar or cardioembolic strokes are not qualifying events), or revascularisation for symptomatic lower limb PAD any time prior to screening Additional risk factors based on the level of the LDL-C and timing of MI or stroke: o Participants with an LDL-C ≥ 75 mg/dL (≥ 1.9 mmol/L) need to have at least one of the other additional risk factors (i to viii) below. ii) T2DM requiring ongoing medical therapy iii) Age ≥ 65 years v) Previous above ankle amputation due to PAD vi) Previous diagnosis of non-end stage CKD 2. Participants at increased risk of a first ASCVD event: Male participant ≥ 50 years of age or female participant ≥ 55 years of age at the time of signing the ICF with LDL-C ≥ 100 mg/dL (≥ 2.6 mmol/L), with no prior history of MI, ischaemic stroke due to atherosclerotic disease, or leg revascularisation for symptomatic lower limb PAD, and with diagnostic evidence of at least one of the following disease categories (i, ii, or iii): (i) Significant atherosclerotic artery disease (ii) High-risk Type 1 or Type 2 diabetes mellitus with manifestation of at least one of the following end-organ diseases: 1. Nephropathy - Persistent (≥ 2 readings) microalbuminuria (urine albumin/creatinine ratio ≥ 30 mg/g) and/or persistent eGFR < 60 mL/min/1.73 m2. At least one reading must come from the medical record within the last 12 months in addition to the reading from screening 2. Retinopathy - Treated diabetic retinopathy (surgical intervention or injectable therapy) or prior diagnosis made by a relevant healthcare specialist 3. Neuropathy - Treated neuropathy (medical therapy for pain relief or symptom alleviation) or prior diagnosis made by a relevant healthcare specialist 4. ABI < 0.9 or > 1.4 - confirmed either in study during screening or randomisation, or from the medical record within the last 5 years (iii) Documented atherosclerosis of less significance For (ii) and (iii), participants need to have at least one of the additional risk factors below: 1. CKD with eGFR x mL/min/1.73 m2 2. Current tobacco use 3. Age ≥ 65 4. T2DM (if included on the less significant atherosclerosis criterion iii) - Participants should receive a background lipid lowering regimen anticipated to achieve at least a ~50% reduction in LDL-C. Except in cases of intolerance, the regimen should include a high intensity statin therapy or lower intensity statin therapy in combination with an oral agent with proven outcome benefit (eg, ezetimibe and/or bempedoic acid). Participants must achieve a stable background lipid lowering therapy > 28 days before screening.

Exclusion Criteria

Any underlying known disease, or condition including homozygous familial hypercholesterolaemia, or LDL or plasma apheresis within 12 months prior to randomisation, that, in the opinion of the investigator, might interfere with the interpretation of the clinical study results. - Any revascularisation procedure planned within the next 3 months. - Available imaging assessment within the last 3 years showing either coronary calcium score of zero, or a coronary computed tomography angiography with no atherosclerosis. - Calculated eGFR < 15 mL /min/1.73 m2 at screening. - Any laboratory values with the following deviations at screening: - AST or ALT > 3 × ULN - TBL > 2 × ULN (except for participants with Gilbert's syndrome where TBL 3 × ULN is acceptable provided direct bilirubin < 1.5 × ULN) - Fasting triglycerides ≥ 400 mg/dL (≥ 4.52 mmol/L). - Creatine kinase > 5 × ULN - Urine albumin/creatinine ratio ≥ 500 mg/g - Uncontrolled T2DM defined as HbA1c ≥ 9.5% at screening. - Inadequately treated hypothyroidism defined as TSH > 1.5 × ULN at screening or participants whose thyroid replacement therapy was initiated or modified within the last 3 months prior to screening. - Use of mipomersen or lomitapide (cholesterol-lowering medications) within 12 months of screening or planned use during the study. - Use of gemfibrozil within one week prior to the Screening Visit or planned use during the study. - Use of PCSK9 inhibitors: evolocumab/alirocumab within 12 weeks of the Screening Visit or planned use during the study, or inclisiran within 18 months of the Screening Visit or planned use during the study, or any other approved PCSK9 inhibitor use within 5 half lives prior to the Screening Visit or planned use during the study.

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: International, multi-centre, randomised, double-blind, placebo-controlled, parallel-group, event-driven
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Placebo controlled

Arm Groups

Arm	Description	Assigned Intervention
Experimental AZD0780	Participants will receive oral AZD0780 once daily	Drug: AZD0780 Participants will receive oral AZD0780 once daily
Placebo Comparator Placebo	Participants will receive oral placebo once daily	Drug: Placebo Participants will receive oral placebo once daily

Recruiting Locations

Research Site
Birmingham, Alabama 35205

Research Site
Fairhope, Alabama 36532

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Foley, Alabama 36535

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Huntsville, Alabama 35801

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Mobile, Alabama 36608

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Saraland, Alabama 36571

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Vestavia Hills, Alabama 35216

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Gilbert, Arizona 85296

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Glendale, Arizona 85308

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Peoria, Arizona 85382

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Phoenix, Arizona 85014

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Phoenix, Arizona 85051

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Phoenix, Arizona 85053

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Scottsdale, Arizona 85260

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Tempe, Arizona 85283

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Tucson, Arizona 85715

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Tucson, Arizona 85745

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Beverly Hills, California 90211

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Canoga Park, California 91303

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Castroville, California 95012

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Chula Vista, California 91911

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Fountain Valley, California 92708

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Garden Grove, California 92844

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Lancaster, California 93534

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Loma Linda, California 92350

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Los Angeles, California 90017

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Los Angeles, California 90035

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Lynwood, California 90262

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Monterey Park, California 91754

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Newport Beach, California 92663

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Norco, California 92860

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Northridge, California 91325

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Pomona, California 91768

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Riverside, California 92503

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San Diego, California 92111

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San Dimas, California 91773

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Santa Ana, California 92705

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Tarzana, California 91356

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Thousand Oaks, California 91360

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West Hills, California 91307

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Waterbury, Connecticut 06708

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Boca Raton, Florida 33486

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Clearwater, Florida 33756

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Coral Gables, Florida 33134

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Crystal River, Florida 34429

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DeLand, Florida 32720

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Fleming Island, Florida 32003

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Fort Lauderdale, Florida 33308

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Hallandale, Florida 33009

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Hialeah, Florida 33012

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Hollywood, Florida 33021

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Homestead, Florida 33030

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Inverness, Florida 34452

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Jacksonville, Florida 32204

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Jacksonville, Florida 32205

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Jacksonville, Florida 32216

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Lake City, Florida 32055

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Lake Worth, Florida 33462

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Lakeland, Florida 33805

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Lakeland, Florida 33813

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Largo, Florida 33777

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Longwood, Florida 32750

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Maitland, Florida 32751

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Margate, Florida 33063

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Miami, Florida 33176

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Miami, Florida 33186

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Miami, Florida 33269

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Miami Lakes, Florida 33014

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Miami Lakes, Florida 33016

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Naples, Florida 34102

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New Port Richey, Florida 34652

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New Port Richey, Florida 34653

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Ocala, Florida 34470

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Orlando, Florida 32801

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Orlando, Florida 32807

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Orlando, Florida 32825

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Palm Harbor, Florida 34684

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Palmetto Bay, Florida 33157

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Pembroke Pines, Florida 33029

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Port Charlotte, Florida 33952

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Safety Harbor, Florida 34695

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Saint Augustine, Florida 32086

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Seminole, Florida 33777

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Tampa, Florida 33625

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West Palm Beach, Florida 33401

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Atlanta, Georgia 30328

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Atlanta, Georgia 30342

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Canton, Georgia 30114

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Decatur, Georgia 30030

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Decatur, Georgia 30033

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Hinesville, Georgia 31313

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Macon, Georgia 31210

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Peachtree Corners, Georgia 30092

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Riverdale, Georgia 30274

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Stockbridge, Georgia 30281

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Tucker, Georgia 30084

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Union City, Georgia 30291

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Chicago, Illinois 60607

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Gurnee, Illinois 60031

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Melrose Park, Illinois 60160

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Tinley Park, Illinois 60477

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Winfield, Illinois 60190

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Carmel, Indiana 46290

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Evansville, Indiana 47714

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Evansville, Indiana 47715

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Munster, Indiana 46321

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Ames, Iowa 50010

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Waterloo, Iowa 50701

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West Des Moines, Iowa 50266

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Kansas City, Kansas 66112

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Kansas City, Kansas 66160

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Wichita, Kansas 67218

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Bowling Green, Kentucky 42101

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Lexington, Kentucky 40503

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Owensboro, Kentucky 42301

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Paducah, Kentucky 42001

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Versailles, Kentucky 40383

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Bossier City, Louisiana 71111

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Covington, Louisiana 70433

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Hammond, Louisiana 70403

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Lake Charles, Louisiana 70601

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Shreveport, Louisiana 71105

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Zachary, Louisiana 70791

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Bangor, Maine 04401

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Scarborough, Maine 04074

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Annapolis, Maryland 21401

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Baltimore, Maryland 21229

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Lanham, Maryland 20706

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Oxon Hill, Maryland 20745

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Pikesville, Maryland 21208

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Boston, Massachusetts 02111

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Brookline, Massachusetts 02446

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Dearborn Heights, Michigan 48127

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Farmington Hills, Michigan 48336

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Southfield, Michigan 48034

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Southfield, Michigan 48076

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Duluth, Minnesota 55805

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Minneapolis, Minnesota 55423

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Minneapolis, Minnesota 55435

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Saint Cloud, Minnesota 56303

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Bridgeton, Missouri 63044

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Chesterfield, Missouri 63005

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Hazelwood, Missouri 63042

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Jefferson City, Missouri 65109

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Kansas City, Missouri 64151

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Springfield, Missouri 65807

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Missoula, Montana 59808

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Elkhorn, Nebraska 68022

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Fremont, Nebraska 68025

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Omaha, Nebraska 68144

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Las Vegas, Nevada 89102

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Las Vegas, Nevada 89119

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Las Vegas, Nevada 89128

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Bridgewater, New Jersey 08807

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Somerset, New Jersey 08873

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Brooklyn, New York 11201

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Buffalo, New York 14217

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Laurelton, New York 11413

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The Bronx, New York 10451

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Durham, North Carolina 27701

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Monroe, North Carolina 28112

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Morehead City, North Carolina 28557

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Morganton, North Carolina 28655

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New Bern, North Carolina 28562

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Wilmington, North Carolina 28401

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Winston-Salem, North Carolina 27157

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Fargo, North Dakota 58104

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Cincinnati, Ohio 45220

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Columbus, Ohio 43213

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Lima, Ohio 45805

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Maumee, Ohio 43537

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Norman, Oklahoma 73069

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Camp Hill, Pennsylvania 17011

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Duncansville, Pennsylvania 16635

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Horsham, Pennsylvania 19044

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Philadelphia, Pennsylvania 19114

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Smithfield, Pennsylvania 15478

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West Chester, Pennsylvania 19380

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Yardley, Pennsylvania 19067

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Providence, Rhode Island 02908

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Fort Mill, South Carolina 29707

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Mauldin, South Carolina 29662

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Myrtle Beach, South Carolina 29572

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North Charleston, South Carolina 29405

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North Charleston, South Carolina 29406

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Rapid City, South Dakota 57701

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Chattanooga, Tennessee 37404

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Chattanooga, Tennessee 37421

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Knoxville, Tennessee 37849

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Knoxville, Tennessee 37912

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Knoxville, Tennessee 37938

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Memphis, Tennessee 38119

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Memphis, Tennessee 38128

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Morristown, Tennessee 37813

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Tullahoma, Tennessee 37388

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Amarillo, Texas 79106

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Beaumont, Texas 77706

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Brownsville, Texas 78526

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Corpus Christi, Texas 78404

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Dallas, Texas 75216

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Dallas, Texas 75234

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Dallas, Texas 75246

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DeSoto, Texas 75115

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El Paso, Texas 79902

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El Paso, Texas 79905

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Euless, Texas 76040

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Houston, Texas 77002

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Houston, Texas 77025

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Houston, Texas 77034

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Houston, Texas 77043

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Houston, Texas 77087

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Humble, Texas 77338

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Irving, Texas 75061

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Katy, Texas 77450

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Kingwood, Texas 77345

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McAllen, Texas 78503

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McKinney, Texas 75069

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Mesquite, Texas 75149

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Paris, Texas 75462

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Pharr, Texas 78577

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Plano, Texas 75093

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San Antonio, Texas 78207

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San Antonio, Texas 78212

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Sugar Land, Texas 77478

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Sugar Land, Texas 77479

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Temple, Texas 76508

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Tomball, Texas 77375

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Tyler, Texas 75701

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Victoria, Texas 77901

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Bountiful, Utah 84010

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Ogden, Utah 84405

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Salt Lake City, Utah 84148

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Falls Church, Virginia 22042

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Hopewell, Virginia 23860

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Manassas, Virginia 20110

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Newport News, Virginia 23606

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Norfolk, Virginia 23504

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Richmond, Virginia 23219

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Suffolk, Virginia 23435

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Redmond, Washington 98052

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Renton, Washington 98057

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Seattle, Washington 98122

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Tacoma, Washington 98405

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Morgantown, West Virginia 26505

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Mayagüez, Puerto Rico 00682

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San Juan, Puerto Rico 00918

Research Site
San Juan, Puerto Rico 00921-3201

More Details

Status: Recruiting
Sponsor: AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.