Randomized, Placebo-controlled, Double-blind, Multicenter Clinical Study to Compare the Efficacy and Safety of the Administration of Three Different Doses of an Anti-SARS-CoV-2 Hyperimmune Equine Serum Formulation in Hospitalized COVID-19 Patients (SECR-02)
试验速览
- 阶段
- 2 期
- 入组人数
- 156
- 试验地点
- 4
- 主要终点
- Crude Mortality in COVID-19 patients
研究概览
简要总结
Passive immunotherapy is a therapeutic alternative used in a variety of infectious diseases including COVID-19. Equine polyclonal hyperimmune sera is a source of neutralizing antibodies against SARS-CoV-2 and a therapeutic alternative under investigation in COVID-19 patients. In the previous study NCT04610502 no significant variations were observed regarding efficacy and safety between two different pharmaceutical preparations of equine hyperimmune sera and adequate tolerability was reported with both investigational products. Formulations were produced through repeated immunization with viral recombinant proteins and contain either antibodies against SARS-CoV-2 S1 protein (S type) or a combination of viral proteins that included S1, N (nuclear), E (envelop) and M (membrane) (M type). Another investigation (NCT04494984) found that the administration of a pharmaceutical preparation similar to the S type produced clinical improvement in hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.
Aim: Evaluate the efficacy and safety of three different doses of an anti-SARS-CoV-2 hyperimmune equine serum formulation (S-type) as an addition to the standard therapeutic approach in adult hospitalized patients with a diagnosis of moderate or severe COVID-19, radiological findings consistent with pneumonia and a symptom onset period not exceeding 10 days.
A total of 156 patients will be included and randomly divided into four groups, each group will receive a different dose of the investigational drug. On day 1, all participants will receive a single intravenous infusion containing the specified dose according to their assigned group. Clinical assessments, laboratory determinations that include: viral load, antibodies quantification, inflammatory and coagulation markers, cytokines levels as well as standard evaluations will be performed for each patient. Data will be collected for all groups on Days 0 to 7, 14 and 28 or at discharge after completion of treatment. The study will end for each participant on the day of discharge from the hospital.
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)
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
- •Subjects male or female, aged 18 and over.
- •Acceptance to participate in the study by the signature of the informed consent by the subject or relative (if applicable).
- •SARS-CoV-2 infection confirmed by reverse transcriptase -polymerase chain reaction (RT-PCR).
- •SARS-CoV-2 pneumonia confirmed by chest X-ray.
- •Patients with moderate or severe disease clinical presentation of the disease that require hospitalization.
- •Being within 10 days of the initial COVID-19 related symptoms onset.
- •Admission in the participating center within a 24hour period.
- •Female patients of child-bearing age with a negative pregnancy test.
排除标准
- •COVID-19 patients that do not require hospitalization (outpatient setting).
- •Patients who are participating in other therapeutic clinical trials.
- •COVID-19 patients who have received convalescent plasma treatment.
- •Critical disease COVID- 19 patients (respiratory failure, septic shock, and/or multiple organ dysfunction, admission PaO2/FIO2 ratio < 100).
- •Previously snake bitten individuals that received any type of equine hyperimmune serum treatment.
- •History of an allergic reaction due to contact or exposure to horses.
- •Pregnant or breastfeeding women.
- •Patients who, at the investigator´s discretion, are not likely to comply with study indications and procedures.
- •Patients currently undergoing hemodialysis in a renal support program.
- •Individuals who were previously classified by their treating physicians (prior to the COVID-19 diagnosis), of having an unfavorable prognosis with a short lifespan due to a concomitant disease other than the study disease.
结局指标
主要结局
Crude Mortality in COVID-19 patients
时间窗: day 7 and 28
The primary endpoint will be the difference in the proportion of deaths from all causes at 7 and 28 days after the administration of the investigational product between the study groups.
次要结局
- Inflammatory markers CRP(Days 0, 1, 2, 3, 5, 7, and 14 or discharge)
- Inflammatory markers IL6(Days 0, 1, 2, 3, 5, 7, and 14 or discharge)
- Modified Sequential Organ Failure Assessment (mSOFA)(Time Frame: Days 0, 1, 2, 3, 5, 7 and 14 or discharge)
- Adverse events(day 28)
- Mechanical ventilation assistance (MVA)(day 28)
- Inflammatory markers Ferritin(Days 0, 1, 2, 3, 5, 7, and 14 or discharge)
- Thrombotic markers PT(Days 0, 1, 2, 3, 5, 7, and 14 or discharge)
- Hospital stay(day 28)
- Inflammatory markers Procalcitonin(Days 0, 1, 2, 3, 5, 7, and 14 or discharge)
- Thrombotic markers PTT(Days 0, 1, 2, 3, 5, 7, and 14 or discharge)
- Changes in viral load(Days 0, 3, 7)
- Thrombotic markers D Dimer(Days 0, 1, 2, 3, 5, 7, and 14 or discharge)
- Thrombotic markers Fibrinogen(Days 0, 1, 2, 3, 5, 7, and 14 or discharge)
- SpO2/FIO2 ratio(Days 0, 1, 2, 3, 4, 5, 6, 7 and 14 or discharge)
- WHO 8 point ordinal scale(Days 0, 1, 2, 3, 4, 5, 6, 7, 14 and 28 or discharge)
- Anti SARS-CoV-2 antibodies(Days 0, 1, 2, 3, 5, 7 and 14 or discharge)