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)

NCT06097663 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CADPT15A122012023-506741-34-00
• Study Type: interventional
• Target: 31
• Locations: 3 countries
• Sites: 6

Brief Summary

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%).

Conditions

Coronary Heart Disease; Clonal Hematopoiesis of Indeterminate Potential (CHIP)

Keywords

coronary heart disease; CHIP; inflammatory marker reduction; NLRP3 inflammasome inhibitor

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Trough Plasma Concentration (Ctrough) of DFV890 at Steady-state

  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

  Day 22, Day 43, Day 64 and Day 85

Study Arms (5)

Treatment Sequence 1

EXPERIMENTAL

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; Drug: DFV890 placebo

Treatment Sequence 2

EXPERIMENTAL

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: MAS825 Placebo; Drug: DFV890; Drug: DFV890 placebo

Treatment Sequence 3

EXPERIMENTAL

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: MAS825 Placebo; Drug: DFV890; Drug: DFV890 placebo

Treatment Sequence 4

EXPERIMENTAL

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; Drug: DFV890

Treatment Sequence 5

PLACEBO COMPARATOR

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: MAS825 Placebo; Drug: DFV890 placebo

Interventions

DFV890 DRUG

Oral tablet of DFV890 active once daily

Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4

MAS825 DRUG

Active MAS825 single dose

Treatment Sequence 1

MAS825 Placebo DRUG

MAS825 placebo single dose

Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4; Treatment Sequence 5

DFV890 placebo DRUG

Oral tablet of DFV890 placebo once daily

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 5

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Washington University

St Louis, Missouri, 63110, United States

Location

Vanderbilt University Medical Cent

Nashville, Tennessee, 37232-8805, United States

Location

Novartis Investigative Site

Montreal, Quebec, H1T 1C8, Canada

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Bonn, 53105, Germany

Location

Novartis Investigative Site

München, 80636, Germany

Location

Related Publications (1)

• 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.

  PMID: 40932796 DERIVED

Related Links

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

MeSH Terms

Conditions

Coronary Disease

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: October 24, 2023
• Study Start: February 15, 2024
• Primary Completion: October 27, 2024
• Study Completion: November 4, 2024
• Last Updated: April 9, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); CA (1); US (2)