A Multicenter Trial Assessing the Impact of Lipoprotein(a) Lowering With Pelacarsen (TQJ230) on the Progression of Calcific Aortic Valve Stenosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy, safety and tolerability of pelacarsen (TQJ230) administered subcutaneously once monthly compared to placebo in slowing the progression of calcific aortic valve stenosis.

Official Title
-----------------
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]

Conditions
-----------------
Aortic Stenosis

Intervention / Treatment
-----------------
* Drug: Pelacarsen (TQJ230) 80mg
* Drug: Matching placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female ≥50 to <80 years of age Lp(a) ≥175 nmol/L at the screening visit, measured at the Central laboratory Mild or moderate calcific aortic valve stenosis At the randomization visit, participant must be optimally treated for existing CV risk factors Exclusion Criteria: Severe calcific aortic valve stenosis Uncontrolled hypertension History of malignancy of any organ system History of hemorrhagic stroke or other major bleeding Platelet count ≤ LLN Active liver disease or hepatic dysfunction Significant kidney disease Pregnant or nursing women Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pelacarsen (TQJ230) 80mg<br>Pelacarsen (TQJ230) 80 mg prefilled syringe injected monthly, administered subcutaneously | Drug: Pelacarsen (TQJ230) 80mg<br>* Pelacarsen (TQJ230) 80mg<br>* Other names: TQJ230;|
| Placebo Comparator: Matching placebo<br>Placebo to match pelacarsen (TQJ230) prefilled syringe injected monthly, administered subcutaneously | Drug: Matching placebo<br>* Matching placebo<br>* Other names: Placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in peak aortic jet velocity | 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 peak aortic jet velocity by echocardiography | 36 months | 
| Change in aortic valve calcium score | 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 | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lp(a) levels | To assess the effect of pelacarsen (TQJ230) vs. placebo on the reduction of Lp(a) levels from baseline to month 12 | 12 months | 
| Change in fibrocalcific thickening of the aortic valve | To assess the effect of pelacarsen (TQJ230) vs. placebo in slowing the progression of CAVS by evaluating the change from baseline to month 36 in fibrocalcific thickening of the aortic valve by contrast CT | 36 months | 
| Time from randomization to first occurrence of composite clinical endpoint event | To assess the effect of pelacarsen (TQJ230) vs. placebo in reducing the risk of composite clinical endpoint defined as reaching either: Unplanned CAVS related hospital admission Aortic valve intervention Death related to calcific aortic valve stenosis | Up to 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cardiovascular, Lipoprotein(a), Lp(a), Hyperlipoproteinemia(a), Calcific aortic valve stenosis, TQJ230, Pelacarsen, Aortic valve stenosis, Aortic stenosis