DII235 for Elevated lipoprotein(a) (Lp(a)) | Atherosclerotic cardiovascular disease | Type 2 diabetes mellitus

Inclusion criteria

• {"criterion_text":"- Signed informed consent must be obtained prior to participation in the study."}
• {"criterion_text":"- Male or female participants 18 to 80 years of age (inclusive) at the screening."}
• {"criterion_text":"- Lp(a) ≥ 150 nmol/L at screening, measured at the central laboratory."}
• {"criterion_text":"- Presence of ASCVD and/or Type 2 diabetes mellitus (T2DM). Diagnosis of ASCVD should be based on at least one of the following: a. Coronary heart disease (CHD): • Prior myocardial infarction (MI) of presumed atherosclerotic origin, which occurred ≥ 12 weeks prior to the Screening Visit • Prior coronary revascularization (PCI or CABG) that occurred ≥ 12 weeks prior to the Screening Visit • Angiographic or CT-imaging (e.g., MDCT/CTA) evidence of coronary atherosclerosis: ≥50% stenosis in at least one major epicardial coronary artery • Coronary artery calcium (CAC) score of ≥ 300 AU by computed tomography (if a participant has T2DM CAC score of ≥ 100 AU is sufficient to define ASCVD) And/or b. Cerebrovascular disease (CeVD): • Prior ischemic stroke, which occurred ≥ 12 weeks prior to the Screening Visit, confirmed by documented brain imaging (CT or MRI); embolic stroke (not of atherosclerotic origin) is not a qualifying event. • History of percutaneous or surgical carotid artery revascularization that occurred ≥ 12 weeks prior to the Screening Visit • Carotid artery stenosis ≥ 70% or symptomatic carotid artery disease with ≥ 50% carotid arterial stenosis on prior angiography or ultrasound And/or c. Peripheral arterial disease (PAD): • Prior non-traumatic amputation of a lower extremity due to peripheral artery disease • History of prior percutaneous or surgical revascularization of iliac, femoral, or popliteal artery • Prior documentation of a resting ankle-brachial index ≤ 0.9 On standard of care treatment for ASCVD risk factors (according to local guidelines and per Investigator discretion). Participants receiving lipid lowering therapy (including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody inhibitors must be on a stable regimen per local guidelines prior to screening, with no planned changes made after screening, and expected to remain on a stable regimen through the end of the treatment (as statins may raise Lp(a) concentrations). A stable dose is defined as at least 8 weeks of treatment at a consistent dose level for monoclonal antibody PCSK9 inhibitors, and at least 4 weeks for all other LLT."}

Exclusion criteria

• {"criterion_text":"- Acute cardiovascular event (e.g., acute myocardial infarction or unstable angina, CABG, stroke, TIA) within 12 weeks before screening"}
• {"criterion_text":"- Renal dysfunction with eGFR ≤ 30 mL/min/1.73 m2 (using CKD-EPI formula) at screening"}
• {"criterion_text":"- Positive human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen tests from central laboratory at Screening Visit."}
• {"criterion_text":"- Hepatic dysfunction based on liver function tests at screening (defined as AST or ALT > 2 × ULN or total bilirubin > 1.5 × ULN at screening) (participants with Gilbert’s syndrome are allowed if total bilirubin < 2 × ULN)"}
• {"criterion_text":"- Current or prior history of moderate to severe heart failure of NYHA Class III or IV, or known LVEF < 30% at screening"}
• {"criterion_text":"- Uncontrolled cardiac arrhythmia"}

Primary endpoints

• {"endpoint_text":"- Time averaged percent change from baseline in Lp(a) measured between Day 60 and Day 180","definition_or_measurement_approach":"Time averaged percent change from baseline in Lp(a)"}
• {"endpoint_text":"- Time averaged percent change from baseline in Lp(a) measured between Day 60 and Day 360","definition_or_measurement_approach":"Time averaged percent change from baseline in Lp(a)"}

Secondary endpoints

• {"endpoint_text":"- Time averaged percent change from baseline in Lp(a) measured (i) between Day 60 and Day 360; and (ii) between Day 240 and Day 360","definition_or_measurement_approach":"Time averaged percent change from baseline in Lp(a)"}
• {"endpoint_text":"- Participant's status of achieving Lp(a) < 125 nmol/L at Day 180 and Day 360 (Yes, No)","definition_or_measurement_approach":"Binary responder status (Lp(a) < 125 nmol/L) at specified days"}
• {"endpoint_text":"- Participant's status of achieving Lp(a) < 75 nmol/L at Day 180 and Day 360","definition_or_measurement_approach":"Binary responder status (Lp(a) < 75 nmol/L) at specified days"}
• {"endpoint_text":"- Incidence of Adverse events, safety laboratory parameters, and vital signs","definition_or_measurement_approach":"Safety assessed by reported adverse events, laboratory tests, and vital sign measurements"}

Germany

Earliest CTIS Part Ii Submission Date

22-12-2025

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

113

Number Of Sites

19

Number Of Participants

72

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA Limited

Responsibilities

1; 3

Name

Parexel International (IRL) Limited

Responsibilities

12; 15: Ancillary supplies

Name

Syneos Health Inc.

Responsibilities

1

Name

Icon Clinical Research Limited

Responsibilities

1

Name

Medpace Reference Laboratories LLC

Responsibilities

15: Oxidized phospholipids and plasminogen sample testing; 4

Name

Labcorp Early Development Laboratories Inc.

Responsibilities

4

Name

Labcorp Central Laboratory Services SARL

Responsibilities

4

Third parties

• {"country":"Germany","full_name":"DATAMAP-Gesellschaft fuer Datenmanagement Datenanalyse und Datenpraesentation mbH","duties_or_roles":"10; 15: Independent statistical group for Data Monitoring Committee (DMC)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"1; 3","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"12; 15: Ancillary supplies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"15: Patient Travel and Reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"15: Patient and site facing material","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"15: Oxidized phospholipids and plasminogen sample testing; 4","organisation_type":"Pharmaceutical company"}