A Phase 2/3, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ABX464 in Treating Inflammation and Preventing COVID-19 Associated Acute Respiratory Failure in Patients Aged ≥ 65 and Patients Aged ≥18 With at Least One Additional Risk Factor Who Are Infected With SARS-CoV-2.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Abivax S.A.
- 入组人数
- 509
- 试验地点
- 30
- 主要终点
- Rate of Responders: i.e. Rate of Patients Who do Not Require Use of High-flow Oxygen Invasive or Non-invasive Mechanical Ventilation (IMV and NIV, Respectively) Within 28 Days and Who Are Alive at the End of the 28 Days Period.
研究概览
简要总结
A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).
详细描述
This phase 2/3 study will evaluate the efficacy and safety of ABX464 50mg QD (oral capsule), on treating inflammation and preventing acute respiratory failure in patients infected with SARS-CoV-2.
Eligible patients will be randomized according to a 2:1 ratio into 2 treatment cohorts as follows:
- Standard of Care + Placebo cohort: 344 patients
- Standard of Care + ABX464 50mg QD: 690 patients
Study design:
The study will consist of 2 periods:
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Blinded treatment bottles
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
- •Adult (≥ 18 years old) men or women, hospitalized or not hospitalized, diagnosed for SARS-CoV-2 infection by PCR, with at least one associated risk factor. Considered risk factors are:
- •Age ≥ 65 years
- •Obesity defined as BMI ≥ 30
- •Recent history of uncontrolled High Blood Pressure (SBP > 150 mm Hg DBP >100 mm Hg) according to investigator
- •Treated diabetes (type I or II)
- •History of ischemic cardiovascular disease
- •Symptomatic patients at enrollment. Symptoms are defined as fever (body temperature ≥ 37.8 C oral/tympanic, or ≥ 38.2 C rectal) for more than 24 hours associated either with headache, sore throat, dry cough, fatigue, chest pain or choking sensation (with no associated respiratory distress), myalgia, anosmia or ageusia.
- •Patients with pulse oximetry arterial saturation ≥ 92 % on room air at enrolment.
- •Patients with the following hematological and biochemical laboratory parameters obtained within 7 days prior to Day 0:
- •Hemoglobin above 9.0 g / dL
- •Absolute Neutrophil Count ≥ 1000 / mm3
- •Platelets ≥ 100 000 mm3;
- •Creatinine clearance ≥ 50 mL / min by the Cockcroft Gault formula
- •Total serum bilirubin < 2 x ULN
- •Alkaline phosphatase < 2 x ULN, AST (SGOT) and ALT (SGPT) < 3 x ULN;
排除标准
- •Patients with moderate or severe acute respiratory failure or requiring noninvasive ventilation or oxygen or with SpO2 < 92% or tachypnea (respiratory rate ≥ 30 breaths/min).
- •Patients treated with immunosuppressors and/or immunomodulators.
- •Engrafted patients (organ and/or hematopoietic stem cells).
- •Patients with uncontrolled auto-immune disease.
- •Patients with known or suspected active (i.e. not controlled) bacterial, viral (excluding COVID-19) or fungal infections.
- •Patients with preexisting, severe and not controlled organ failure.
- •History or active malignancy requiring chemotherapy or radiation therapy (excluding 2 years disease free survivor patients).
- •Pregnant or breast-feeding women.
- •Illicit drug or alcohol abuse or dependence that may compromise the patient's safety or adherence to the study protocol.
- •Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer.
- •Hypersensitivity to ABX464 and/or its excipients.
- •Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.
研究组 & 干预措施
ABX464
ABX464 - Capsules + Standard of Care (SOC)
干预措施: ABX464 (Drug)
Placebo
Placebo - Capsules + Standard of Care (SOC)
干预措施: Placebo (Drug)
结局指标
主要结局
Rate of Responders: i.e. Rate of Patients Who do Not Require Use of High-flow Oxygen Invasive or Non-invasive Mechanical Ventilation (IMV and NIV, Respectively) Within 28 Days and Who Are Alive at the End of the 28 Days Period.
时间窗: 28 days
Subjects will be assessed as responders if they did not receive oxygen supplementation through IMV and NIV during the treatment period, and they are alive at the end of the 28-days treatment period. Non responders are subjects who receive oxygen supplementation (through IMV and NIV during the treatment period) and/or who die during the 28-days treatment period. The use of high-flow oxygen being defined as settings of 3 L/min or greater AND with at least one SpO2 measurement \< 92%, with or without O2 supplementation). Descriptive statistics will be presented by treatment arm.
次要结局
- Rate of Patients Hospitalized(28 days)
- Percentage of Patients Reporting Each Severity Rating on a 7-point Ordinal Scale(28-day treatment period)
- Change From Enrolment in Inflammatory Markers in Plasma and in Immune Phenotype and Assessment of Cell-activation Markers in PBMCs(at each study visit during the 28-day treatment period)
- Rate of Patients Requiring Oxygen Supplementation(28-day treatment period)
- Time to Hospitalization(28-day treatment period)
- Time to Assisted Ventilation and Oxygen Supplementation(28-day treatment period)
- Change From Baseline in microRNA-124 Levels(at each study visit during the 28-day treatment period)
- Change From Baseline in CRP, Troponin I & T and D-dimer(at each study visit during the 28-day treatment period)
- SARS-CoV-2 Viral Load(at each study visit during the 28-day treatment period)
- Number and Rates of Participants With Treatment Emergent Adverse Event(From D0 to D48 (28 days treatment period + up to 20 days Safety follow-up period))