Study to Evaluate the Safety and Effectiveness of an Immunobiological Drug (Anti SARS-CoV-2) in the Treatment of Coronavirus Disease 2019 (CoViD-19)
试验速览
- 阶段
- 2 期
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Change in time needed to clinical improvement
研究概览
简要总结
The aims of this study is to analyze the efficacy and safety of a passive immunotherapy strategy using hyperimmune equine serum known as Anti-SARS-CoV-2 elaborated by the National Institute for the Production of Biologicals (ANLIS-Malbrán) as an addition to the standard therapeutic approach for hospitalized patients with COVID-19, in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection aged 18 to 80 years.
详细描述
This is an adaptive phase II/III study that aims to analyze the efficacy and safety of a immunobiological drug (Anti SARS-CoV-2) in the treatment of CoViD-19. This treatment is a passive immunotherapy strategy developed as a purified F(ab')2 fraction of equine hyperimmune serum (Anti-SARS-CoV-2). The equine serum was generated from antigenic stimulation with the SARS-CoV-2 receptor binding domain (RBD) purified protein.
This type of product (equine hyperimmune serum F(ab')2) has been widely used in our country in the last 100 years with satisfactory results and an acceptable safety profile in the treatment of accidents with poisonous animals such as anti-loxosceles, anti -latrodectus, anti-scorpionic, and anti-phoneutria, anti-bothropic, anti-micrurus, and anti-crotalic sera, all developed by the National Institute of Biological Production (ANLIS-Malbrán) and distributed free of charge in public hospitals in the country .
In the present study, evaluates the effect and safety of this immunobiological treatment in patients with COVID-19 that require hospitalization.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Subjects over 18 years old and under 80 years old.
- •Positive results by RT-PCR for SARS CoV-2
- •Clinical picture compatible with respiratory compromise in the form of pneumonia attributed to COVID-19 (Stage 3, 4 or 5 according to the WHO scale), lasting up to 72 hours from the onset of symptoms to their evaluation to be incorporated into the study.
- •Patient with good disposition towards the study and that signs the informed consent.
排除标准
- •Patients with clinical disease corresponding to mild / asymptomatic forms (Absence of radiological infiltrate and risk factors, with normal auscultation and arterial saturation of oxygen (SatO2) greater than 95%)
- •Patients with clinical disease corresponding to severe forms (Severe pneumonia: presence of severity criteria (ATS / IDSA), one of two major or three minor criteria.)
- •Patients who have received other therapeutic strategies in the framework of an experimental study that make it difficult to evaluate the results obtained, including (but not limited to): convalescent plasma, lopinavir / ritonavir, hydroxychloroquine, and azithromycin.
- •Pregnant or lactating women.
- •Women of childbearing potential not using an effective contraceptive method (withdrawal, intrauterine device, or oral contraceptives).
- •History of severe anaphylactic reaction with the administration of equine plasma.
- •Patients with comorbidities that justify a risk of high mortality from causes independent of SARS-CoV-2 infection (eg, stage IV cancer)
- •Patient who does not consent to participate.
研究组 & 干预措施
Anti-SARS-CoV-2
Administration of 10 ml of a concentrated equine hyperimmune serum solution with neutralizing activity of SARS-CoV-2 not less than1/5120, administered in slow intravenous infusion (10 ml diluted in100 ml of physiological solution, administered over 50 to 60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0 when incorporated into the study -initial dose- and at 48 hours -second dose-).
干预措施: Anti-SARS-CoV-2 (Drug)
Placebo
Administration of 10 ml of a control-solution with no-neutralizing activity of SARS-CoV-2, administered in slow intravenous infusion (10ml diluted in 100 ml of physiological solution, administered over 50 to60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0when incorporated into the study -initial dose- and at 48 hours -second dose-).
干预措施: Placebo (Drug)
结局指标
主要结局
Change in time needed to clinical improvement
时间窗: Reached each day between day 1 and 28 post-inclusion in the study
In subjects admitted to the general ward for active infection by SARS-CoV-2 and a clinical picture of pneumonia who receive supportive treatment recommended by the guidelines of the Ministry of Health of the Argentine Nation (Population), if slow intravenous administration of Anti SARS-CoV-2 in two doses 48 hours apart (Intervention) added to supportive treatment, compared to supportive treatment alone (patients will receive slow intravenous administration of a placebo solution in two doses 48 hours apart to maintain the "blind" as Comparator), changes the time needed to clinical improvement (Outcome), during 28 days after the assignment (Time).
次要结局
- Change in the number of patients in each World Health Organization (WHO) Ordinal Scale Category (0 to 8 being 0 better and 8 worse)(days 7, 14 and 21 post-inclusion)
- Change in Mortality rate(28 days post-inclusion)
- Change in Mechanical Ventilation Requirement rate(28 days post-inclusion)
- Change in duration of oxygen treatment requirement(28 days post-inclusion)
- Change in Length of Hospitalization(28 days post-inclusion)
- Change in frequency of nosocomial infection(28 days post-inclusion)
- Change in Lymphocyte cell count(28 days post-inclusion)
- Change in viral RNA Negativization rate on nasopharyngeal swab test(7, 14, 21, and 28 days post-inclusion)
- Description of adverse events type and frequency(28 days post-inclusion)
- Requirement of additional treatments for Adverse Drug reactions(28 days post-inclusion)
- Describe the AUC of purified F(ab')2 Anti-SARS-CoV-2(Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days)
- Describe the Cmax of purified F(ab')2 Anti-SARS-CoV-2(Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days)
- Describe the t1/2 of purified F(ab')2 Anti-SARS-CoV-2(Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days)
- Describe the Ke of purified F(ab')2 Anti-SARS-CoV-2(Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days)
研究者
Guillermo Alberto Keller
Physician. Specialist in internal medicine and clinical pharmacology
Administracion Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran