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%).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
31
Active MAS825 single dose
MAS825 placebo single dose
Oral tablet of DFV890 active once daily
Oral tablet of DFV890 placebo once daily
Washington University
St Louis, Missouri, United States
Vanderbilt University Medical Cent
Nashville, Tennessee, United States
Novartis Investigative Site
Montreal, Quebec, Canada
Novartis Investigative Site
Bonn, Germany
Novartis Investigative Site
Frankfurt, Germany
Novartis Investigative Site
München, Germany
Serum levels of IL-6 and IL-18
To evaluate the effect of various dose levels of DFV890 versus placebo to reduce circulating levels of inflammatory markers in participants with coronary heart disease and CHIP
Time frame: From Day 22 to Day 92 (end of study)
Serum level of IL-6
To evaluate the effect of MAS825 versus placebo to reduce circulating levels of inflammatory markers in participants with coronary heart disease and CHIP.
Time frame: Day 22
Plasma trough concentrations (Ctrough) of DFV890 at steady-state
To assess the pharmacokinetics of DFV890 in participants with coronary heart disease and CHIP.
Time frame: From Day 22 to Day 92
Serum concentrations of MAS825 after a single s.c. dose of MAS825
To assess the pharmacokinetics of MAS825 in participants with coronary heart disease and CHIP.
Time frame: From Day 1 to Day 85
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