A randomized double-blind, placebo-controlled, multicenter trial assessing the impact of lipoprotein(a) lowering with pelacarsen (TQJ230) on the progression of calcific aortic valve stenosis [Lp(a)FRONTIERS CAVS]

Phase 2

Recruiting

• Conditions: Calcific Aortic Valve Stenosis

• Registration Number: 2022-502135-19-00
• Lead Sponsor: Novartis Pharma AG

Brief Summary

To demonstrate the superiority of pelacarsen (TQJ230) versus placebo in slowing the progression of calcific aortic valve stenosis by evaluating the change from baseline to month 36 in peak aortic jet velocity by echocardiography and,

To demonstrate the superiority of pelacarsen (TQJ230) vs. placebo in slowing the progression of calcific aortic valve stenosis by evaluating the change from baseline to month 36 in aortic valve calcium score by computed tomography

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-02
• Study First Submitted QC: 2022-12-02
• Study First Posted: 2022-12-12
• Study Start: 2024-03-07
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-11
• Last Update Posted: 2025-07-16
• Primary Completion: 2030-03-12
• Study Completion: 2030-03-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Not specified
• Target Recruitment: 264

Inclusion Criteria

Male and female ≥50 to <80 years of age

Lipoprotein(a) ≥175 nmol/L at Screening-Part I, measured at the central laboratory

Mild or moderate calcific aortic valve stenosis as defined by a peak aortic jet velocity ≥2.5 m/s and ≤3.5 m/s at Screening-Part II, as assessed by the core laboratory

At the randomization visit, participant must be optimally treated for existing CV risk factors (e.g. LDL-C, Diabetes Mellitus and hypertension according to local practice/guidelines)

Exclusion Criteria

Severe calcific aortic valve stenosis defined by mean gradient >40 mmHg or aortic valve area <1 cm2 at Screening-Part II, as assessed by the core laboratory

History of hemorrhagic stroke or other major bleeding

Platelet count <140,000 per mm3

Active liver disease or hepatic dysfunction

Significant kidney disease

Pregnant or nursing women

Planned aortic valve intervention

Unicuspid valve or other congenital cardiac anomaly (bicuspid aortic valve morphology is not excluded), at Screening-Part II, as assessed by the core laboratory

Severe mitral valve stenosis (valve area <1.5 cm2), severe mitral valve regurgitation, or severe aortic valve regurgitation at Screening-Part II, as assessed by the core laboratory

Inability to undergo or to acquire an optimal echocardiogram or computed tomography, or contraindication to computed tomography contrast media

Left ventricular ejection fraction <55% at Screening-Part II, as assessed by the core laboratory

Heart failure New York Heart Association class III - IV at Screening-Part II or at Randomization visit (Day 1)

Uncontrolled hypertension

History of malignancy of any organ system

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in peak aortic jet velocity from baseline to month 36		Change in peak aortic jet velocity from baseline to month 36
Change in aortic valve calcium score from baseline to month 36		Change in aortic valve calcium score from baseline to month 36

Secondary Outcome Measures

Name	Time	Method
Change in lipoprotein(a) levels from baseline to month 12		Change in lipoprotein(a) levels from baseline to month 12
Change in fibrocalcific thickening of the aortic valve from baseline to month 36		Change in fibrocalcific thickening of the aortic valve from baseline to month 36
Time from randomization to first occurrence of composite clinical endpoint event, defined as reaching either: • Unplanned CAVS related hospital admission • Aortic valve intervention • Death related to calcific aortic valve stenosis		Time from randomization to first occurrence of composite clinical endpoint event, defined as reaching either: • Unplanned CAVS related hospital admission • Aortic valve intervention • Death related to calcific aortic valve stenosis
Safety endpoints (including adverse events/serious adverse events, safety laboratory parameters, vital signs) collected from baseline to end of study		Safety endpoints (including adverse events/serious adverse events, safety laboratory parameters, vital signs) collected from baseline to end of study

Trial Locations

Locations (32)

Heart Center Research Llc; 🇺🇸 Huntsville, Alabama, United States

Cardiovascular Res Found; 🇺🇸 Beverly Hills, California, United States

National Heart Institute; 🇺🇸 Beverly Hills, California, United States

Foothill Cardiology; 🇺🇸 Covina, California, United States

Valley Clinical Trials; 🇺🇸 Northridge, California, United States

University Of California San Diego; 🇺🇸 San Diego, California, United States

UC San Francisco Medical Center; 🇺🇸 San Francisco, California, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Excel Medical Clinical Trials LLC; 🇺🇸 Boca Raton, Florida, United States

Inpatient Research Clinical LLC; 🇺🇸 Miami Lakes, Florida, United States

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