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)

A Randomized, Placebo-controlled, Parallel-group, Investigator- and Participant-blinded Phase 2a Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 and MAS825 for Inflammatory Marker Reduction in an Adult Population With Coronary Heart Disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP)

This Phase 2a clinical trial evaluated 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 (variant allele frequency [VAF] ≥2%).

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease; Clonal Hematopoiesis of Indeterminate Potential (CHIP)
• Intervention / Treatment: Drug: MAS825; Drug: DFV890 placebo; Drug: MAS825 Placebo; Drug: DFV890

Detailed Description

This was a multi-center, randomized, placebo-controlled, participant- and investigator-blinded study.

The study consisted of a screening period up to 30 days; a treatment period of approximately 12 weeks with an end of treatment (EOT) visit on Day 85, which is one day after the last dose of DFV890 or placebo; a follow-up period of approximately 1 week; and a standard safety follow-up call approximately 30 days following the last dose. The overall study duration is approximately 21 weeks.

Participants were randomized to one of five treatment sequences. Based on the treatment sequence assignments, participants started on either a combination of MAS825 and placebo, DFV890 and placebo, or placebo and placebo on Day 1, and then, within each DFV890 treatment sequence, participants received up-titrating doses of DFV890 or placebo at the corresponding study visits. None of the treatment sequences included a combination of both active DFV890 and active MAS825.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Novartis Investigative Site
• Germany
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • München, Germany, 80636
    • Novartis Investigative Site
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Novartis Investigative Site
• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • Tennessee
    • Nashville, Tennessee, United States, 37232-8805
      • Vanderbilt University Medical Cent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence 1; On Day 1, participants received the single s.c. dose of MAS825 and DFV890 oral placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 84.	Drug: MAS825; Active MAS825 single dose; Drug: DFV890 placebo; Oral tablet of DFV890 placebo once daily
Experimental: Treatment Sequence 2; On Day 1, participants received the single s.c. dose of MAS825 placebo and DFV890 oral placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 22 when participants started receiving DFV890 10mg QD. The dose of DFV890 was uptitrated to 25mg on Day 43 and to 100mg on Day 64.	Drug: DFV890 placebo; Oral tablet of DFV890 placebo once daily; Drug: MAS825 Placebo; MAS825 placebo single dose; Drug: DFV890; Oral tablet of DFV890 active once daily
Experimental: Treatment Sequence 3; On Day 1, participants received the single s.c. dose of MAS825 placebo and DFV890 oral placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 22 when participants started receiving DFV890 25mg QD. The dose of DFV890 was uptitrated to 50mg on Day 43 and to 100mg on Day 64.	Drug: DFV890 placebo; Oral tablet of DFV890 placebo once daily; Drug: MAS825 Placebo; MAS825 placebo single dose; Drug: DFV890; Oral tablet of DFV890 active once daily
Experimental: Treatment Sequence 4; On Day 1, participants received the single s.c. dose of MAS825 placebo and DFV890 10 mg QD. Participants continued receiving DFV890 10 mg QD until Day 22 when the dose of DFV890 was uptitrated to 25mg QD. On Day 43 the dose of DFV890 was uptitrated to 50mg and on Day 64 to 100mg.	Drug: MAS825 Placebo; MAS825 placebo single dose; Drug: DFV890; Oral tablet of DFV890 active once daily
Placebo Comparator: Treatment Sequence 5; On Day 1, participants received the single s.c. dose of MAS825 placebo and DFV890 oral placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 84.	Drug: DFV890 placebo; Oral tablet of DFV890 placebo once daily; Drug: MAS825 Placebo; MAS825 placebo single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio to Baseline Serum Levels of IL-6 for DFV890 Based on an Emax Model	Serum levels of IL-6 at 3 weeks after the start of a dosing period for DFV890. The circulating serum levels of the cytokine IL-6 were measured by a validated enzyme-linked immunosorbent assay (ELISA) assay at a qualified vendor. The Emax model selected for IL-6 analysis was a model with 2 covariates (IL-6 baseline and bodyweight) and 1 random effect.	Baseline (before first dose of study drug), 3 weeks after the start of a dosing period for DFV890 (between Day 22 and Day 85, depending on treatment sequence assignment)
Ratio to Baseline Serum Levels of IL-18 for DFV890 Based on an Emax Model	Serum levels of IL-18 at 3 weeks after the start of a dosing period for DFV890. The circulating serum levels of the cytokine IL-18 were measured by a validated enzyme-linked immunosorbent assay (ELISA) assay at a qualified vendor. The Emax model selected for IL-18 was a model with one covariate (IL-18 baseline) and 1 random effect.	Baseline (before first dose of study drug), 3 weeks after the start of a dosing period for DFV890 (between Day 22 and Day 85, depending on treatment sequence assignment)
Ratio to Baseline Serum Levels of IL-6 for MAS825 Based on a Traditional Linear Regression Model	Serum level of IL-6 at Week 3 for MAS825. The circulating serum levels of the cytokine IL-6 was measured by a validated enzyme-linked immunosorbent assay (ELISA) assay at a qualified vendor. Data was analyzed with a a traditional linear regression model including treatment as a fixed categorical effect, a random intercept effect for participant, and the baseline value of the biomarker and baseline body weight as covariates.	Baseline (before first dose of study drug), 3 weeks after a single MAS825 dose on Day 1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Plasma Concentration (Ctrough) of DFV890 at Steady-state	Ctrough is the observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval.	After the last dose of each 3-week dosing period: Day 22 pre-dose, Day 43 pre-dose, Day 64 pre-dose, or Day 85, depending on treatment sequence assignment
MAS825 Serum Concentrations	MAS825 serum concentrations were determined using a validated target-based sandwich ELISA.	Day 22, Day 43, Day 64 and Day 85

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Sumida K, Obeng EA, Kovesdy CP. Clonal Hematopoiesis in Kidney Disease. Clin J Am Soc Nephrol. 2025 Sep 11. doi: 10.2215/CJN.0000000895. Online ahead of print. No abstract available.

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Actual): October 27, 2024
• Study Completion (Actual): November 4, 2024

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: October 18, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: coronary heart disease; CHIP; inflammatory marker reduction; NLRP3 inflammasome inhibitor
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: CADPT15A12201; 2023-506741-34-00 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No