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)

NCT ID: NCT06097663

Last Updated: 2024-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

31 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-15

Study Completion Date

2024-11-04

Brief Summary

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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%).

Detailed Description

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

The study consists 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 will be randomized to one of five treatment sequences. Based on the treatment sequence assignments, participants will start 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 will receive up-titrating doses of DFV890 or placebo at the corresponding study visits.

Conditions

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Coronary Heart Disease Clonal Hematopoiesis of Indeterminate Potential (CHIP)

Keywords

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coronary heart disease CHIP inflammatory marker reduction NLRP3 inflammasome inhibitor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Treatment Sequence 1

Treatment Sequence 1

Group Type EXPERIMENTAL

MAS825

Intervention Type DRUG

Active MAS825 single dose

DFV890 placebo

Intervention Type DRUG

Oral tablet of DFV890 placebo once daily

Treatment Sequence 2

Treatment Sequence 2

Group Type EXPERIMENTAL

MAS825 Placebo

Intervention Type DRUG

MAS825 placebo single dose

DFV890

Intervention Type DRUG

Oral tablet of DFV890 active once daily

DFV890 placebo

Intervention Type DRUG

Oral tablet of DFV890 placebo once daily

Treatment Sequence 3

Treatment Sequence 3

Group Type EXPERIMENTAL

MAS825 Placebo

Intervention Type DRUG

MAS825 placebo single dose

DFV890

Intervention Type DRUG

Oral tablet of DFV890 active once daily

DFV890 placebo

Intervention Type DRUG

Oral tablet of DFV890 placebo once daily

Treatment Sequence 4

Treatment Sequence 4

Group Type EXPERIMENTAL

MAS825 Placebo

Intervention Type DRUG

MAS825 placebo single dose

DFV890

Intervention Type DRUG

Oral tablet of DFV890 active once daily

Treatment Sequence 5

Treatment Sequence 5

Group Type PLACEBO_COMPARATOR

MAS825 Placebo

Intervention Type DRUG

MAS825 placebo single dose

DFV890 placebo

Intervention Type DRUG

Oral tablet of DFV890 placebo once daily

Interventions

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MAS825

Active MAS825 single dose

Intervention Type DRUG

MAS825 Placebo

MAS825 placebo single dose

Intervention Type DRUG

DFV890

Oral tablet of DFV890 active once daily

Intervention Type DRUG

DFV890 placebo

Oral tablet of DFV890 placebo once daily

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Washington University

St Louis, Missouri, United States

Site Status

Vanderbilt University Medical Cent

Nashville, Tennessee, United States

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Bonn, , Germany

Site Status

Novartis Investigative Site

Frankfurt, , Germany

Site Status

Novartis Investigative Site

München, , Germany

Site Status

Countries

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United States Canada Germany

References

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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.

Reference Type DERIVED
PMID: 40932796 (View on PubMed)

Other Identifiers

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2023-506741-34-00

Identifier Type: OTHER

Identifier Source: secondary_id

CADPT15A12201

Identifier Type: -

Identifier Source: org_study_id