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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)

Primary Purpose

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

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
MAS825
MAS825 Placebo
DFV890
DFV890 placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Heart Disease focused on measuring coronary heart disease, CHIP, inflammatory marker reduction, NLRP3 inflammasome inhibitor

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Treatment Sequence 1

    Treatment Sequence 2

    Treatment Sequence 3

    Treatment Sequence 4

    Treatment Sequence 5

    Arm Description

    Treatment Sequence 1

    Treatment Sequence 2

    Treatment Sequence 3

    Treatment Sequence 4

    Treatment Sequence 5

    Outcomes

    Primary Outcome Measures

    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
    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.

    Secondary Outcome Measures

    Plasma trough concentrations (Ctrough) of DFV890 at steady-state
    To assess the pharmacokinetics of DFV890 in participants with coronary heart disease and CHIP.
    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.

    Full Information

    First Posted
    October 18, 2023
    Last Updated
    October 24, 2023
    Sponsor
    Novartis Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06097663
    Brief Title
    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)
    Official Title
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 15, 2023 (Anticipated)
    Primary Completion Date
    January 15, 2026 (Anticipated)
    Study Completion Date
    January 15, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Novartis Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Coronary Heart Disease, Clonal Hematopoiesis of Indeterminate Potential (CHIP)
    Keywords
    coronary heart disease, CHIP, inflammatory marker reduction, NLRP3 inflammasome inhibitor

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    28 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment Sequence 1
    Arm Type
    Experimental
    Arm Description
    Treatment Sequence 1
    Arm Title
    Treatment Sequence 2
    Arm Type
    Experimental
    Arm Description
    Treatment Sequence 2
    Arm Title
    Treatment Sequence 3
    Arm Type
    Experimental
    Arm Description
    Treatment Sequence 3
    Arm Title
    Treatment Sequence 4
    Arm Type
    Experimental
    Arm Description
    Treatment Sequence 4
    Arm Title
    Treatment Sequence 5
    Arm Type
    Placebo Comparator
    Arm Description
    Treatment Sequence 5
    Intervention Type
    Drug
    Intervention Name(s)
    MAS825
    Intervention Description
    Active MAS825 single dose
    Intervention Type
    Drug
    Intervention Name(s)
    MAS825 Placebo
    Intervention Description
    MAS825 placebo single dose
    Intervention Type
    Drug
    Intervention Name(s)
    DFV890
    Intervention Description
    Oral tablet of DFV890 active once daily
    Intervention Type
    Drug
    Intervention Name(s)
    DFV890 placebo
    Intervention Description
    Oral tablet of DFV890 placebo once daily
    Primary Outcome Measure Information:
    Title
    Serum levels of IL-6 and IL-18
    Description
    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)
    Title
    Serum level of IL-6
    Description
    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
    Secondary Outcome Measure Information:
    Title
    Plasma trough concentrations (Ctrough) of DFV890 at steady-state
    Description
    To assess the pharmacokinetics of DFV890 in participants with coronary heart disease and CHIP.
    Time Frame
    From Day 22 to Day 92
    Title
    Serum concentrations of MAS825 after a single s.c. dose of MAS825
    Description
    To assess the pharmacokinetics of MAS825 in participants with coronary heart disease and CHIP.
    Time Frame
    From Day 1 to Day 85

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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. Other protocol-defined inclusion/exclusion criteria may apply
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Phone
    1-888-669-6682
    Email
    novartis.email@novartis.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Novartis Pharmaceuticals
    Phone
    +41613241111
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Novartis Pharmaceuticals
    Organizational Affiliation
    Novartis Pharmaceuticals
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing 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

    Learn more about this trial

    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)

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