A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 and MAS825 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP)

• Status: Recruiting
• Trial end date: 2026-02-24
• Target enrollment: 0
• Participant gender: All

Summary

This Phase 2a clinical trial will evaluate the effectiveness, safety, and tolerability of increasing dose strengths of an oral daily medication, DFV890, administered for 12 weeks, or a single s.c. dose of MAS825, to reduce key markers of inflammation related to CVD risk, such as IL-6 and IL-18, in approximately 28 people with known coronary heart disease and TET2 or DNMT3A CHIP (VAF ≥2%).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals

Criteria

Inclusion Criteria:

• Male and female participants aged between 18 - 80 years (inclusive) at the start of screening will be included.

• Participants must have a body mass index (BMI) within the range of 18 - 40 kg/m2 at screening. BMI = Body weight (kg) / [Height (m)]2.

• Documented spontaneous myocardial infarction (MI) (diagnosed according to the universal MI criteria with or without evidence of ST segment elevation) at least 30 days before the start of screening (Thygesen et al 2007).

• Known presence of CHIP, restricted to driver mutations in TET2 or DNMT3A with a VAF ≥2%, as documented in the participant's medical history.

• For participants on statin therapy (HMG-CoA reductase inhibitor) as clinically indicated, participants must be on a stable regimen (at least 4 weeks before randomization), with no planned statin dose changes over the course of the trial treatment period. Unplanned statin dose changes during the trial treatment period may occur.

Exclusion Criteria:

• Patients receiving concomitant medications that are known to be strong or moderate inducers of cytochrome CYP2C9 enzyme and/or strong inducers of CYP3A, strong inhibitors of CYP2C9 and/or strong or moderate inhibitors of CYP3A and the treatment cannot be discontinued or switched to a different medication within 5 half-lives or 1 week (whichever is longer) prior to Day 1 and for the duration of the study.

• At screening, pre-malignant clonal cytopenias or clonal cytopenia of unknown significance (CCUS).

• History of ongoing, chronic, or major recurrent infectious disease, at the discretion of the Investigator, at the start of screening.

• Patients with suspected or proven immunocompromised state at screening.

• Use of any biologic drugs targeting the immune system within 26 weeks of Day 1.

• Multi-vessel coronary artery bypass graft (CABG) surgery within the past 3 years prior to the start of screening.

• Planned coronary revascularization (percutaneous coronary intervention (PCI) or CABG) or any other major surgical procedure during the study (until End of Study (EOS)).

• Symptomatic Class IV heart failure (New York Heart Association [NYHA]) at the start of screening.

Other protocol-defined inclusion/exclusion criteria may apply