A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Elevated hsCRP

A Randomized, Placebo-controlled, Parallel-group, Investigator- and Participant-blinded Phase 2a Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Elevated hsCRP

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, to reduce key markers of inflammation related to CVD risk, such as IL-6 and IL-18, in approximately 24 people with known heart disease and an elevated marker of inflammation, hsCRP.

Study Overview

• Status: Completed
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Drug: DFV890; Drug: DFV890 Placebo

Detailed Description

This was a multi-center, randomized, placebo-controlled, participant- and investigator-blinded study to evaluate the efficacy, safety, and tolerability of intra-individual dose escalation of DFV890 for inflammatory marker reduction in participants with coronary heart disease and elevated hsCRP. The study consisted of a screening period of up to 60 days, a treatment period of approximately 12 weeks, an end of treatment (EOT) visit on Day 85, which was one day after the last dose on Day 84, a follow-up period of approximately 1 week and a standard safety-follow-up call approximately 30 days following the last dose.

Participants meeting all eligibility criteria were randomized in a 5:5:1:1 ratio to one of four treatment sequences (three DFV890 treatment sequences or a placebo-only sequence). The dose of DFV890 was uptitrated (according to the specific treatment sequence that the participant was assigned to) approximately every three weeks at the scheduled visits on Days 22, 43 and 64.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Novartis Investigative Site
• United States
  • California
    • Northridge, California, United States, 91325
      • Valley Clinical Trials
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials LLC
    • Jacksonville, Florida, United States, 32209
      • UF Health Science Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27410
      • Triad Clinical Trials LLC
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Monument Health Clinical Research
  • Washington
    • Tacoma, Washington, United States, 98405
      • Universal Research Group LLC

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 - 85 years (inclusive) at the start of screening will be included.
• Subjects must have a body mass index (BMI) within the range of 18 - 45 kg/m2. 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.
• Participants must have hsCRP levels ≥ 2 mg/L at two timepoints during screening. Screening values must be separated by a minimum of 8 days. The initial hsCRP value must be a minimum of 30 days after the qualifying MI or after any percutaneous coronary intervention (PCI) performed separately from the qualifying MI.
• 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.
• Patients with suspected or proven immunocompromised state at screening
• History of ongoing, chronic, or major recurrent infectious disease, at the discretion of the investigator, at the start of 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 6 months prior to the start of screening.
• Symptomatic Class IV heart failure (New York Heart Association) at the start of screening.
• Planned coronary revascularization (PCI or CABG) or any other major surgical procedure during the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence 1; On Day 1, participants received 1 tablet of DFV890 matching placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 22 when they started receiving DFV890 10 mg QD. The dose of DFV890 was uptitrated to 25 mg on Day 43 and to 100 mg on Day 64.	Drug: DFV890; Oral film-coated tablets of DFV890 once daily; Drug: DFV890 Placebo; Oral film-coated tablets of DFV890 placebo once daily
Experimental: Treatment sequence 2; On Day 1, participants received 1 tablet of DFV890 matching placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 22 when they started receiving DFV890 25 mg QD. The dose of DFV890 was uptitrated to 50 mg on Day 43 and to 100 mg on Day 64.	Drug: DFV890; Oral film-coated tablets of DFV890 once daily; Drug: DFV890 Placebo; Oral film-coated tablets of DFV890 placebo once daily
Experimental: Treatment sequence 3; On Day 1, participants received 1 tablet of DFV890 10 mg QD. Participants continued receiving DFV890 10 mg QD until Day 22 when they started receiving DFV890 25 mg QD. The dose of DFV890 was uptitrated to 50 mg on Day 43 and to 100 mg on Day 64.	Drug: DFV890; Oral film-coated tablets of DFV890 once daily
Placebo Comparator: Treatment sequence 4; On Day 1, participants received 1 tablet of DFV890 matching placebo QD. Participants continued receiving DFV890 oral placebo QD until Day 84.	Drug: DFV890 Placebo; Oral film-coated tablets of DFV890 placebo once daily

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 analysis was a model with 2 covariates (IL-18 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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Plasma Concentration (Ctrough)	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

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2023
• Primary Completion (Actual): December 17, 2024
• Study Completion (Actual): December 23, 2024

Study Registration Dates

• First Submitted: September 4, 2023
• First Submitted That Met QC Criteria: September 4, 2023
• First Posted (Actual): September 11, 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; Phase 2a; DFV890; elevated hsCRP
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Coronary Disease; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: CDFV890F12201

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