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

Primary Purpose

Coronary Heart Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
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 DFV890, Phase 2a, coronary heart disease, elevated hsCRP

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. Subjects must have a body mass index (BMI) within the range of 18 - 40 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 3 years 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.

Sites / Locations

  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Treatment Sequence 1

Treatment sequence 2

Treatment sequence 3

Treatment sequence 4

Arm Description

Participants will be administered Placebo and different doses of DFV890

Participants will be administered Placebo and different doses of DFV890

Participants will be administered different doses of DFV890

Participants will be administered Placebo

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 elevated hsCRP

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 elevated hsCRP

Full Information

First Posted
September 4, 2023
Last Updated
October 24, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT06031844
Brief Title
A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 18, 2023 (Actual)
Primary Completion Date
March 5, 2025 (Anticipated)
Study Completion Date
March 13, 2025 (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, 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.
Detailed Description
This is 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 consists 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 is 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. The overall study duration is approximately 24 weeks and approximately 24 participants will be enrolled into the trial. Participants meeting all eligibility criteria will be 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 will be uptitrated (according to the specific treatment sequence that the participant is assigned to) approximately every three weeks at the scheduled visits on Days 22, 43 and 64.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Heart Disease
Keywords
DFV890, Phase 2a, coronary heart disease, elevated hsCRP

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Sequence 1
Arm Type
Experimental
Arm Description
Participants will be administered Placebo and different doses of DFV890
Arm Title
Treatment sequence 2
Arm Type
Experimental
Arm Description
Participants will be administered Placebo and different doses of DFV890
Arm Title
Treatment sequence 3
Arm Type
Experimental
Arm Description
Participants will be administered different doses of DFV890
Arm Title
Treatment sequence 4
Arm Type
Placebo Comparator
Arm Description
Participants will be administered Placebo
Intervention Type
Drug
Intervention Name(s)
DFV890
Intervention Description
oral film-coated tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
oral film-coated tablets
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 elevated hsCRP
Time Frame
From Day 22 to End of Study Visit (up to 92 days)
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 elevated hsCRP
Time Frame
From Day 22 to End of Study Visit (up to 92 days)

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. Subjects must have a body mass index (BMI) within the range of 18 - 40 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 3 years 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.
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
Facility Information:
Facility Name
Novartis Investigative Site
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Individual Site Status
Recruiting

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

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

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