International, Double Blind, Randomized, Placebo-controlled Study to Evaluate the Effect on Parameters of Systemic Inflammation and Disease Outcomes and Safety of RPH-104 in Subjects With Acute ST-elevation Myocardial Infarction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 11
- 主要终点
- High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure)
研究概览
简要总结
The goal of the study was to evaluate the effect of single administration of RPH-104 at 80 mg and 160 mg on parameters of systemic inflammation and outcomes of the disease in subjects with ST-segment elevation myocardial infarction (STEMI)
详细描述
After signing the informed consent form, the investigator assessed the subject's eligibility for the study. The following procedures were performed during the screening: collection of medical history, recording previous and concomitant therapy, demographic data, recording 12-lead ECG findings on which STEMI diagnosis was based, recording date and time of STEMI symptom development, recording date, time and results of coronary angiography (CAG) at admission to the study site, measurement of blood neutrophil count, vital signs, physical examination including measurement of body weight (if hospital bed is available), blood sampling for hematology, biochemistry, determination of concentration of hsCRP and brain natriuretic peptide (BNP; N-terminal (NT)-pro hormone brain natriuretic peptide (NT-pro-BNP)), for females with retained reproductive potential - pregnancy test (test strips).
The subjects meeting selection criteria were randomized to one of the three groups (in 1:1:1 ratio) for single subcutaneous administration of RPH-104 80 mg, RPH-104 160 mg or placebo.
Screening, randomization and administration of the study products were made on the same (first) study day.
Further 4-week (28-day) clinical follow-up and additional 6- and 12-month clinical follow-up period were performed.
The end of clinical part of the study was the date of the last visit of the last subject within additional 12-month clinical follow-up.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who gave voluntary written Informed consent to participate in the study and to follow all Protocol procedures.
- •STEMI diagnosis defined as chest pain or its equivalent with ECG findings evidencing ST elevation (>1 mm) in two or more consecutive leads or acute left bunch branch block according the investigator's judgement.
- •Percutaneous coronary intervention (PCI) with stenting was performed within no more than 12 hours after onset of chest pain or its equivalent and randomization was performed in no more than 12 hours after PCI (overall within 24 hours of onset of chest pain or equivalent).
- •Consent of female subjects with childbearing potential defined as all female subjects with physiological potential to conceive, to use highly effective contraceptive methods throughout the study starting from screening (signing Informed Consent Form) and negative pregnancy test.
- •Highly effective contraceptive methods include combination of two of the following methods (a+b or a+c or b+c):
- •oral, injection or implanted hormonal contraceptives; in case of oral contraceptives, the female subjects should administer the same product for at least 3 months prior to the study therapy;
- •intrauterine device or contraceptive system;
- •barrier methods: condom or occlusive cap (diaphragm or cervical cap / vaginal fornix cap) with spermicidal foam/gel/film/cream/vaginal suppository
- •Ability and willingness of the subject, according to the reasonable investigator's judgment, to attend the study site at all scheduled visits, undergo the study procedures and follow the Protocol requirements including subcutaneous injections by qualified site personnel.
排除标准
- •Hypersensitivity to test product (RPH-104) and/or its ingredients/excipients.
- •Pregnancy and breastfeeding.
- •Verified chronic heart failure (The American Heart Association / The American College of Cardiology (AHA/ACC) C-D class, New York Heart Association (NYHA) Functional class (FC) III-IV)
- •Pre-existing severe valvular heart disease according to the investigator's assessment.
- •Pre-existing left ventricular (LV) dysfunction (ejection fraction (EF)<40%)
- •History of STEMI
- •Complications of acute myocardial infarction (MI) in the form of acute left ventricular failure and cardiogenic shock defined as stable blood pressure decrease (SBP<90 mm Hg) associated with signs of hypoperfusion as well as cases when inotropic and/or mechanical support is required to maintain SBP; and / or unstable hemodynamics.
- •Active infections (acute or chronic); active tuberculosis.
- •Recent (less than 5 half-life periods) or current administration of colchicine, as well as agents with an immunosuppressant mechanism of action, including, but not limited to:
- •glucocorticoids at doses of > 1 mg/kg of methylprednisolone equivalent, tumor necrosis factor-alfa (TNFα) blockers, Interleukin-1 (IL-1) and other biological drugs, cyclosporine and other immunosuppressants. Non-steroidal anti-inflammatory drugs (NSAIDs) are allowed.
- •Immunization with live vaccines within 90 days prior to the study product administration.
- •Chronic systemic autoimmune or autoinflammatory diseases
- •Suspected necessity in cardiosurgery.
- •Oncology (or diagnosis of oncology within the last 5 years).
- •History of organ transplantation or necessity in transplantation at the screening initiation or scheduled transplantation during the study.
- •Neutropenia (absolute neutrophil count <1800/mm^3).
- •Participation in another clinical study within the previous 3 months prior to Screening visit.
- •Other medical (including mental) conditions or abnormal laboratory findings which may increase the risk for the subject associated with the study participation or administration of the study products or which may affect interpretation of the study results and, according to the investigator, render the subject ineligible for the study.*
- •*If, in the Investigator's opinion, administration of a non-live COVID-19 (SARS-CoV-2) vaccine increases the risk for the patient related to his/her participation in the study, the Investigator can make a decision not to include this patient into the study.
- •The subjects working at the study site or subjects working for Sponsor directly involved in this clinical study.
研究组 & 干预措施
RPH-104 80 mg
subjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites
干预措施: RPH-104 80 mg (Biological)
RPH-104 80 mg
subjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites
干预措施: Placebo (Drug)
RPH-104 160 mg
subjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of (80 mg) of RPH-104 on different administration sites
干预措施: RPH-104 80 mg (Biological)
Placebo
subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites
干预措施: Placebo (Drug)
结局指标
主要结局
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure)
时间窗: Day 1 until Day 14
hsCRP area under curve (AUC) from baseline (Day 1) until Day 14
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (сomplete Cases)
时间窗: Day 1 until Day 14
hsCRP area under curve (AUC) from baseline (Day 1) until Day 14
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Multiple Imputation Procedure)
时间窗: Day 1 until Day 14
hsCRP area under curve (AUC) from baseline (Day 1) until Day 14 (sensitivity analysis)
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Complete Cases)
时间窗: Day 1 until Day 14
hsCRP area under curve (AUC) from baseline (Day 1) until Day 14 (sensitivity analysis)
次要结局
- Changes in Levels of Brain Natriuretic Peptide (BNP) During 12-month Follow-up Period Compared to Baseline(From Day 1 until Day 365)
- BNP AUC From Day 1 (Baseline) Until Day 28(up to Day 28)
- hsCRP AUC From Baseline Until Day 28 (Complete Cases)(up to Day 28)
- Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period(up to Day 365)
- Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline(From Day 1 Until Day 365)
- Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF or Emergency Outpatient Visits Due to HF During 12-month Follow-up Period(up to Day 365)
- Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF During 12-month Follow-up Period(up to Day 365)
- Changes in Regional LV Function After 12 Months Compared to Baseline(From Day 1 Until Day 365)
- hsCRP AUC From Baseline Until Day 28 (Multiple Imputation Procedure)(up to Day 28)
- NT-pro-BNP AUC From Day 1 (Baseline) Until Day 28(up to Day 28)
- Changes in Levels of Brain Natriuretic Peptide (NT-proBNP) During 12-month Follow-up Period Compared to Baseline(From Day 1 until Day 365)
- Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline(From Day 1 Until Day 365)
- Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline(From Day 1 Until Day 365)
- Number of Patients With of Hospitalizations Due to Heart Failure (HF) or Other Cardiac Reasons Not Associated With HF, or Due to Non-cardiac Reasons During 12-month Follow-up Period(up to Day 365)
- Number of Patients With New Cases of HF During 12-month Follow-up Period(up to Day 365)
- Changes in Stroke Volume (SV) Compared to Baseline(From Day 1 Until Day 365)
- Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline(From Day 1 Until Day 365)
- Changes in Global Longitudinal Strain (GLS) Compared to Baseline(From Day 1 Until Day 365)
- Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline(From Day 1 Until Day 365)
- Changes in hsCRP Levels During the Study Compared to Baseline(From Day 1 until Day 28)
- Changes of Fractional Area Change (FAC) Compared to Baseline(From Day 1 Until Day 365)
- Changes in Mitral Valve (MV) e'Sept Compared to Baseline(From Day 1 Until Day 365)
- Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline(From Day 1 Until Day 365)
- Changes in Mitral Valve e'Lat Compared to Baseline(From Day 1 Until Day 365)