A Randomized, Double Blind, Multicenter, Placebo Controlled, Parallel Group, Exploratory Efficacy and Safety Study of Glenzocimab in SARS-Cov-2-related Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Progression from moderate to severe respiratory distress assessed at Day 4
研究概览
简要总结
A randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study to evaluate the efficacy and safety of glenzocimab in ARDS.
详细描述
This randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study evaluates the efficacy and safety of glenzocimab in ARDS.
Patients will be screened for eligibility and all tests should have results prior to any randomization, so as to avoid screening failures to a maximum extent. The turn-around time for these tests should be comprised within 24hrs to allow for rapid inclusions if needed. Eligible patients (n=68) will be randomized in a 1:1 ratio to glenzocimab or placebo. Patient inclusions will be fractioned into sequential (3-day apart) cohorts of growing size (2, 4 then 6 patients), each balanced between glenzocimab and placebo in order to check safety in a gradual manner. A Data Safety Monitoring Board (DSMB) will meet after 12 patients will have been accrued, and again after the first 30 patients.
Glenzocimab will be administered by IV infusion. The dosing regimen will be 1000mg for 3 days. All patients will receive in parallel the best medical care at the discretion of the investigating center, or per local guidelines. The allocation of each patient in any given center to an active treatment or placebo will strictly follow a central randomization scheme. The study period will be of a maximum of 40 days per patient. Patients will be closely monitored during the first 7 days following randomization with complete evaluations being performed at 24 hrs, 48 hrs, 72 hrs, then on Days 4 (96 hrs), 5 (120 hrs), 7 (+/-1 day), 14 (+/-2 days), 20 (+/-2 days), 40 (+/-3 days). Should a patient being discharged before Day 40, distant consultations by telemedicine may be undertaken if it is not deemed desirable that the patient comes back to the institution.
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)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female hospitalized patients ≥ 18 years (i.e., at least 18 years old at the time of randomization), having given their written consent.
- •Having a positive RT-PCR test for COVID-19
- •Presenting with symptoms of COVID-19, including:
- •Shortness of breath or difficulty breathing OR at least 2 of the following
- •Fever, defined as any body temperature 38°C
- •Repeated shaking with chills
- •Muscle pain
- •Sore throat
- •New loss of taste or smell
- •Presenting with signs of moderate but progressive pulmonary disease with:
- •respiratory symptoms (cough, dyspnea, etc.),
- •uni- or bilateral ground-glass opacities, or pulmonary infiltrates on chest radiograph and/or CT scan,
- •clinical and biological evidence of progression over the past 48hrs.
- •Effective birth control that should have been in place for at least 2 months in non-menopausal women and 4 months for men after IMP administration. Birth control methods considered to be highly effective include:
- •combined (estrogen-progestogen) hormonal contraception associated with the inhibition of ovulation: oral, intravaginal, transdermal,
- •progesterone-only hormonal contraception associated with the inhibition of ovulation: oral, injectable, implantable,
- •intrauterine device,
- •intrauterine hormone-releasing system,
- •bilateral tubal occlusion,
- •vasectomized partner.
- •Women of child-bearing potential must have negative results of a urinary or plasma pregnancy test (serum HCG).
排除标准
- •Patients requiring immediate admission to the ICU,
- •Patients requiring invasive mechanical ventilation,
- •ARDS of another origin,
- •Concomitant pulmonary infection (pneumoniae) with another agent, notably bacterial or fungal,
- •Patients under immunosuppressive agents,
- •Childbirth within <10 days,
- •Pregnancy or breastfeeding,
- •Prior cardiopulmonary resuscitation <10 days,
- •Allergy or hypersensitivity to drugs of the same class
- •Participation in another interventional clinical trial within 30 days prior to the inclusion.
研究组 & 干预措施
glenzocimab 1000 mg
干预措施: glenzocimab (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Progression from moderate to severe respiratory distress assessed at Day 4
时间窗: Day 4
Progression from moderate to severe assessed at Day 4 is a composite failure endpoint defined as the occurrence of at least one of the following failure events : * Respiratory rate (RR) ≥ 30/min, or * Oxygen Saturation (SpO2) ≤ 93% in resting state, or * Oxygen Pressure/ Inspired fraction (PaO2/FiO2) ≤ 200mmHg * Death occurring prior to or on Day 4
次要结局
- Admission to the ICU(Up to Day 40)
- ICU-free days(Up to Day 40)
- Hospital-free days(Up to Day 40)
- Oxygen-free days(Up to Day 40)
- Clinical recovery and Time to Clinical recovery(Up to Day 40)
- Cure and Time-to-cure(Up to Day 40)
- Incidence, nature and severity of Adverse Events, SAEs, SUSARs and Treatment-Emergent Adverse Events (TEAEs)(Up to Day 40)
- Incidence of bleeding-related events(Up to Day 40)
- Incidence of hypersensitivity reactions(Up to Day 40)
- Changes from baseline on blood pressure(Up to Day 40)
- Changes from baseline on heart rate(Up to Day 40)
- Changes from baseline on INR/PTT(Up to Day 40)
- Changes from baseline on platelet count(Up to Day 40)
- Changes from baseline on plasma fibrinogen level(Up to Day 40)
- Changes from baseline on plasma D-Dimers level(Up to Day 40)
- Changes from baseline on serum-glucose level(Up to Day 40)
- Changes from baseline on LDH level(Up to Day 40)
- All cause mortality at day 40(Day 40 (maximum))
- WHO-COVID-19 Scale(Up to Day 40)
- NEWS-2 Scale(Up to Day 40)
- Respiratory Rate status (RR)(Up to Day 40)
- Hypoxemia status(Up to Day 40)
- SpO2 status(Up to Day 40)
- CHEST CT-Scan (or in exceptional cases, chest radiogram)(Day 4)
- Changes from baseline on NFS(Up to Day 40)
- Changes from baseline on urea level(Up to Day 40)
- Changes from baseline on IL6 level(Up to Day 40)
- Changes from baseline on Tnt(Up to Day 40)
- Changes from baseline on creatinemia(Up to Day 40)
- Changes from baseline on LFTs (ASAT/ALAT)(Up to Day 40)
- Changes from baseline on CRP level(Up to Day 40)
- Changes from baseline on NT proBNP(Up to Day 40)
- Changes from baseline on procalcitonin level(Up to Day 40)
- Changes from baseline on ferritin level(Up to Day 40)
- ECG over the course of the study versus screening(Up to Day 40)