A Multi-Center Open-Label Study, Evaluating Safety and Preliminary Efficacy of Allocetra-OTS for the Treatment and Prevention of Organ-Failure Deterioration in Severe and Critical Patients With COVID-19 and Respiratory Dysfunction
试验速览
- 阶段
- 2 期
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Assessment of safety by determining the number of participants with any Adverse Events (AE) and Serious Adverse Events (SAE)
研究概览
简要总结
This is a multi-center, open-label study evaluating the safety of Allocetra-OTS, in up to 24 subjects with severe COVID-19 and respiratory dysfunction. Subjects, who will be identified as suffering from COVID-19, will be recruited.
After signing an informed consent by the patient and, within 24+6 hours following the time of eligibility (time 0), on Day 1, eligible recipient subjects will receive single intravenous (IV) administration of investigational product as described below.
Subjects will be hospitalized for COVID-19, and later as medically indicated. Following the investigational product (IP) administration (Day 1), subjects will be followed for efficacy and safety assessments through 28 days.
详细描述
Study Rationale
COVID-19, the name given to the clinical syndrome associated with the newly recognized virus SARS-CoV-2, has become pandemic with a mortality estimated between 1-4% and complications among hospitalized patients leading to up to 15-25% of hospital admissions being admitted to the intensive care unit (ICU).
The term "cytokine storm" calls up vivid images of an immune system gone awry and an inflammatory response flaring out of control. The term has captured the attention of the public and the scientific community alike and is increasingly being used in both the popular media and the scientific literature. Indeed, a few publications have indicated an important part of the complications in COVID-19 are related to the cytokine storm (Huang et al. Lancet 2020, Mehta et al. Lancet 2020).
In a clinical study conducted in sepsis patients with Allocetra-OTS (ClinicalTrials.gov Identifier: NCT03925857) we observed that administration of Allocetra-OTS to patients with sepsis was safe and had a significant immuno-modulating effect, leading to resolution of the cytokine storm in these patients. There were indications that this treatment may also be efficacious, based on comparisons with mortality score prediction and historical matched-controls, and the resolution of organ dysfunction compared to matched historical controls.
A recent study published by Zou et al (Lancet 2020) showed increasing odds of in-hospital death in these COVID-19 patients associated with older age and higher Sequential Organ Failure Assessment (SOFA) score on admission.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
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
- •Up to twenty-four subjects, male or female > 18 and < 80-year-old diagnosed with COVID-19, as defined below:
- •Laboratory confirmation of SARS-COV2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source.
- •Patients classified as severe or critical according to NIH severity classification.
- •All patients will be treated by treating physician with S.C. Clexane, at a minimal dose of 40 mg a day
- •Illness with at least one of the following:
- •Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
- •SpO2 ≤ 94% on room air, OR
- •Requiring supplemental oxygen, with a P/F ratio of ≤350, ≥150
- •Signed written informed consent by the patient.
排除标准
- •Pregnancy, lactation, and childbearing potential woman who are not willing to use acceptable contraceptives measures for the entire study duration.
- •Combined with other organ failures (need organ support not including respirator), including Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30)
- •Patients with a malignant tumor, other serious systemic diseases and psychosis.
- •Patients who are participating in other clinical trials or treated with any experimental agents that may contradict this trial (i.e, biologics)
- •Co-Infection of HIV, tuberculosis.
- •Known immunocompromised state or medications known to be immunosuppressive (see concomitant prohibited medications on the next page).
- •Intubated patients (due to inability to sign an informed consent)
- •Patients with P/F or S/F ratio of <150 or a change in status of eligibility manifested by a rapid decline of P/F ratio between eligibility status and actual drug delivery.
结局指标
主要结局
Assessment of safety by determining the number of participants with any Adverse Events (AE) and Serious Adverse Events (SAE)
时间窗: 28 days follow up
Incidence rates and severity of any Adverse Events (AE) and Serious Adverse Events (SAE)
次要结局
- Preliminary Efficacy: Recovery from COVID-19 as determined by negative PCR or asymptomatic by the NIH classification for the severity of illness(28 days follow up)
- Life support(28 days follow up)
- Support measurements: improvement of severity rating on a 7-point ordinal scale(28 days follow up)
- Mortality(28 days follow up)
- Clinical status by the new NIH Patient Classification for the severity of illness(28 days follow up)
- Preliminary Efficacy: To assess prevention of respiratory deterioration associated with COVID-19 by measuring the PaO2/FiO2 ratio(On days, 3, 5, 7, 14, and 28 during 28 days follow up)
- Hospitalization(28 days follow up)
- Clinical status by NEWS2(28 days follow up)
- Support measurements: percentage of subjects reporting each severity rating on a 7-point ordinal scale(28 days follow up)
- Exploratory: Serum cytokines/chemokines and immunomodulating factors(28 days follow up)
- Exploratory: complete blood counts(28 days follow up)
- Exploratory: Histone and cell-free DNA levels(28 days follow up)
- Virus Clearance(Within the 28 days follow up, tested on days 14 and 28)
研究者
Mevorach Dror
Professor & Head, Department of Internal Medicine B; Head, Rheumatology Research Center, Hadassah and the Hebrew University Medical School
Hadassah Medical Organization