Immune Responses to COVID-19 (SARS-CoV-2 Related Infection); Isolation of Human Neutralizing Monoclonal Antibodies for Therapeutics and Vaccine Design Approaches: a Prospective Monocentric Trial With Collaborative Sample Collection.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Isolation of recombinant monoclonal neutralizing antibodies directed against SARS-CoV-2, isolated from COVID19 hospitalized patients blood probes.
研究概览
简要总结
According to different projections, the COVID-19 outbreak currently happening in France and worldwide could result in millions of deaths in the absence of efficient therapies. The COVID-19 causative agent, the SARS-CoV-2, is a virus leading to respiratory system infections in human and for which there is currently no vaccine or treatment scientifically validated in clinical studies.
In that context, therapeutic human neutralizing antibodies targeting the SARS-CoV-2 envelop glycoproteins and which enable inhibition of the viral replication represent an innovative therapeutic alternative with great potential. These antibodies are also critical tools for vaccine development.
Simultaneously, CHUGA researchers coordinate with each other to set up a collective biological collection to achieve others objectives such as biomarkers identifications.
详细描述
A RELIRE PAR PASCAL POIGNARD
- CURRENT KNOWLEDGE ABOUT THE PATHOLOGY
Coronaviruses are a large family whose members share a tropism for epitheliums. They are usually responsible of ordinary and frequent infections in humans, with acute and limited inflammation of the respiratory tract. The fact that they are RNA viruses (which confers them an important plasticity), and that some types infect animals and others infect human, explain that they may be a source of new human diseases arising from animal strains. This is how two Coronavirus outbreaks spreading in several countries emerged in the past years: The Severe Acute Respiratory Syndrome (SARS), in 2003; and the Middle East Respiratory Syndrome (MERS) in 2012. In January 2020, another coronavirus outbreak has been described: the COVID-19 outbreak, related to the SARS-CoV-2.
The disease mentioned as coronavirus disease 2019 (COVID-19) has been detected for the first time in China in December 2019; a first case cluster was strongly related to a live-animal market, suggesting an animal origin; the following descriptions did clearly established a human-to-human transmission, with a reproduction number (R0) between 2.5 and 3.5. Some scientific publications described potential contaminations by asymptomatic subjects. While China finally managed to record a great decrease in the number of daily cases (82,241 total cases with 3,309 deaths on the 31st March 2020), the epidemic rapidly reached many other countries. In France, several sites of active virus circulation (l'Oise, Mulhouse, la Haute-Savoie) finally led to an important development of the epidemic in France (44,450 cases with 3,024 deaths on March 31st 2020).
The disease consists in a pneumonia reminding of the Acute Respiratory Distress Syndrome (ARDS) in several aspects; after a 5 days median incubation time, symptoms develops with cough which can be febrile/feverish, and which can evolve/develop towards dyspnea, and in some instance towards ARDS after 7 to 10 days of evolution. If the first epidemiological descriptions stated a high proportion of severe cases (more than 33%), a study including more than 70,000 cases then suggested that 15% cases were severe/marked, and 5% critical; however, it is likely that asymptomatic or little symptomatic cases can be numerous, according to new studies. To date, no curative antiviral treatment demonstrated clinical efficacy but many clinical trials are ongoing. This disease is a problem for the healthcare system for two reasons: its contagiousness (which require major social distancing measures) and its morbidity (which paralyze the healthcare system by requiring too much ICU hospitalization). 2. IMMUNE RESPONSES IN COVID-19 STATE OF ART:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Man or woman over 18 years old hospitalized in Grenoble University hospital for a COVID-19 infection for less than 48 hours,
- •Symptomatic patient with an estimated hospitalization period over 7 days and requiring regular blood sampling,
- •Patient weighing more than 60 kg.
- •Patient who has given his non-opposition/consent for AcNT study.
- •Patient affiliated toFrench Social Security System.
排除标准
- •Patient non able to consent (such as intubated patient in ICU)
- •Patient protected by the French law (defined as: minor, pregnant or breastfeeding woman, patient under curatorship, patient deprived of liberty or hospitalized against his/her will)
- •Patient already included in a clinical trial involving substantial blood sampling (over 20mL a day or over 150mL a month).
- •Patient whose medical condition is not compatible with the trial (impossibility to consent, intensive case unit, anaemia with haemoglobin under 10g/dl... )
结局指标
主要结局
Isolation of recombinant monoclonal neutralizing antibodies directed against SARS-CoV-2, isolated from COVID19 hospitalized patients blood probes.
时间窗: From patient and time frame identified in step 1 described above.
STEP 2 : Ability to produce monoclonal recombinant antibodies anti-SARS-CoV-2 from memory B cell (fundamental outcome : yes/no)
次要结局
- Description of biological biomarkers (cytokine, IL6) predictive of worsening(day 1)
- Description of biological biomarkers (cytokine, IL10) predictive of worsening(day 1)
- Description of biological biomarkers (Cellular immune responses, lymphocytes) predictive of worsening(day 1)
- Description of biological biomarkers (Cellular immune responses, monocytes) predictive of worsening(day 1)
- Description of biological biomarkers (complement system, CH50) predictive of worsening(day 1)
- Description of biological biomarkers (complement system, CH50a) predictive of worsening(day 1)
- Description of biological biomarkers (complement system, C3) predictive of worsening(day 1)
- Description of biological biomarkers (complement system, C4) predictive of worsening(day 1)
