A clinical trial to learn more about the effects of DII235 in people with high levels of lipoprotein(a)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Phenomena and Processes [G] - Metabolism [G03]

Trial duration

26 Jan 2026 → ongoing

Decision date (initial)

2026-01-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2025-521912-21-00

WHO UTN

U1111-1324-2184

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Dose response, Safety, Pharmacokinetic, Efficacy

1. To evaluate the dose-response relationship of DII235 administered as compared to placebo on time averaged percentage change from baseline of Lp(a) in adults with elevated Lp(a) (defined as Lp(a) ≥ 150 nmol/L).
2. To evaluate the efficacy of DII235 versus placebo in time averaged percent change from baseline in Lp(a) between Day 60 and Day 360.

Secondary objectives 4

1. To evaluate the efficacy of DII235 versus placebo in time averaged percent change from baseline in Lp(a), (i) between Day 60 and Day 360 (except those covered by the primary objectives); and (ii) between Day 240 and Day 360
2. To evaluate the proportion of participants achieving Lp(a) < 125 nmol/L for DII235 dose regimens compared to placebo at Day 180 and Day 360
3. To evaluate the proportion of participants achieving Lp(a) < 75 nmol/L for DII235 dose regimens compared to placebo at Day 180 and Day 360
4. To evaluate the safety and tolerability of DII235 compared to placebo

Conditions and MedDRA coding

Cardiovascular risk reduction in participants with elevated Lp(a)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Signed informed consent must be obtained prior to participation in the study.
2. Male or female participants 18 to 80 years of age (inclusive) at the screening.
3. Lp(a) ≥ 150 nmol/L at screening, measured at the central laboratory.
4. 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 6

1. Acute cardiovascular event (e.g., acute myocardial infarction or unstable angina, CABG, stroke, TIA) within 12 weeks before screening
2. Renal dysfunction with eGFR ≤ 30 mL/min/1.73 m2 (using CKD-EPI formula) at screening
3. Positive human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen tests from central laboratory at Screening Visit.
4. 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)
5. Current or prior history of moderate to severe heart failure of NYHA Class III or IV, or known LVEF < 30% at screening
6. Uncontrolled cardiac arrhythmia

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Time averaged percent change from baseline in Lp(a) measured between Day 60 and Day 180
2. Time averaged percent change from baseline in Lp(a) measured between Day 60 and Day 360

Secondary endpoints 4

1. 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
2. Participant's status of achieving Lp(a) < 125 nmol/L at Day 180 and Day 360 (Yes, No)
3. Participant's status of achieving Lp(a) < 75 nmol/L at Day 180 and Day 360
4. Incidence of Adverse events, safety laboratory parameters, and vital signs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 11

Locations

1 EU/EEA country · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications