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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 14
- 主要终点
- Serum levels of IL-6 and IL-18
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/m
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: DFV890 Placebo (Drug)
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.
干预措施: DFV890 Placebo (Drug)
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.
干预措施: DFV890 Placebo (Drug)
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.
干预措施: DFV890 (Drug)
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.
干预措施: DFV890 (Drug)
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.
干预措施: DFV890 (Drug)
结局指标
主要结局
Serum levels of IL-6 and IL-18
时间窗: From Day 22 to End of Study Visit (up to 92 days)
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
Ratio to Baseline Serum Levels of IL-6 for DFV890 Based on an Emax Model
时间窗: 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)
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.
Ratio to Baseline Serum Levels of IL-18 for DFV890 Based on an Emax Model
时间窗: 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)
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.
次要结局
- Plasma trough concentrations (Ctrough) of DFV890 at steady state(From Day 22 to End of Study Visit (up to 92 days))
- Trough Plasma Concentration (Ctrough)(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)