A Phase 2/3, Adaptive, Randomized, Controlled, Double-blind Study to Investigate the Pharmacokinetics, Efficacy and Safety of the Hyperimmune Equine Serum (INM005) in Adult Patients With Moderate to Severe Confirmed SARS-CoV-2 Disease.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 243
- 试验地点
- 28
- 主要终点
- Clinical changes in COVID-19 symptoms
研究概览
简要总结
This study aims to analyze the efficacy and safety of passive immunotherapy by administering an equine hyperimmune serum (INM005) against the SARS-CoV-2 receptor binding domain (RBD) to COVID-19 patients. Improvement of the clinical course 28 days after the start of treatment will be evaluated.
详细描述
The pandemic caused by the new coronavirus has generated a situation unprecedented in recent history, with several million infected and hundreds of thousands of deaths. This disease is easily transmissible by air. Although a high percentage of cases present mild clinical presentation, approximately 15% of patients present moderate to severe cases and 5% require critical care, with respiratory assistance and a high risk of mortality. No effective therapies for the treatment or prevention of SARS-CoV-2 have been identified yet. Preliminary evidence indicates that passive immunotherapy with convalescent plasma could alter the clinical course of this infection in a favorable manner. This strategy, even if confirmed as successful, requires voluntary donation by patients who have recovered, not all of whom are eligible as donors, since the antibody response varies in magnitude in different patients. This adaptive stage II/III study aims to analyze the efficacy and safety of passive immunotherapy by administering a purified Fab fraction of equine hyperimmune serum (INM005) generated from antigenic stimulation with the SARS-CoV-2 RBD protein, with the objective of neutralizing the interaction of SARS-CoV-2 with its cellular receptor, thus preventing the multiplication of the virus. The safety of this type of equine hyperimmune sera has already been demonstrated in previous and ongoing protocols with a biologically equivalent product against the E. Coli shiga toxin to treat patients with Hemolytic Uremic Syndrome (CT-INM004-01 and CT-INM004-02). In the present study, eligible patients will with moderate to severe symptoms of COVID-19 that require hospitalization will receive two 4 mg/kg doses of INM005, two days apart, with the aim of improving the clinical course of COVID-19 28 days after the start of treatment with the study drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
A Double-blind, Placebo-controlled, sealed-envelope based. Access to unblinded interim results will be limited to the DMC and unblinded statistician
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects of both sexes aged 18 to 79 years of age
- •SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) for virus detection
- •Patients with moderate or severe disease by NIH definition, which requires hospitalization.
- •Acceptance to participate in the study by the signature of the informed consent by a subject or their relative, if applicable
- •Be within 10 days of the onset of symptoms at the time of the Screening visit according to a case definition from the National Ministry of Health
- •Female patients of child-bearing age with negative pregnancy test
排除标准
- •Patients who have received treatment with plasma from COVID-19 convalescents.
- •Patients who are participating in other therapeutic clinical trials
- •Patients who require mechanical respiratory assistance or are hospitalized in the ICU at the time of the screening visit.
- •History of anaphylaxis, prior administration of equine serum (por example, anti-tetanus serum or anti-ophidic serum or anti-arachnid toxin serum) or allergic reaction due to contact or exposure to horses.
- •Pregnant or breastfeeding women
- •Patients who, at the doctor's discretion, are likely to die within the next 30 days due to a concomitant disease other than the study disease
- •Patients who are expected to be referred to another institution within 72 hours of enrollment, which prevents proper follow-up of that patient.
研究组 & 干预措施
Placebo
Subjects will receive a 1st intravenous dose of Placebo and a 2nd intravenous dose of Placebo. Each dose will be separated by 48 h (± 2 h).
干预措施: Placebo (Drug)
Active
Subjects will receive a 1st intravenous dose of 4 mg/kg INM005 (Anti-SARS-CoV-2 hyperimmune equine immunoglobulin F[ab']2 fragments) and a 2nd intravenous dose of 4 mg/kg of INM005. Each dose will be separated by 48 h (± 2 h).
干预措施: INM005 (Drug)
结局指标
主要结局
Clinical changes in COVID-19 symptoms
时间窗: 4 weeks
The primary endpoint will be the proportion of patients who show a change in symptoms 28 days after the administration of the first dose. A responding subject is defined as a subject with improvement in at least 2 categories on the 8-point World Health Organization (WHO) ordinal scale of clinical status or a subject who is discharged.
Number of Participants With Improvement in at Least Two Categories in WHO 8-point Ordinal Clinical Scale at Day 28 or Discharge
时间窗: Discharge or up to Day 28
The primary endpoint will be the proportion of patients who showed improvement 28 days after the administration of the first dose. A responding subject is defined as a subject with improvement in at least 2 categories on the 8-point World Health Organization (WHO) ordinal scale of clinical status or a subject who is discharged. The ordinal scale measures illness severity over time, the minimum value is 0 and the maximum value is 8. The higher is the score, the worse is the outcome. Detailed scale: 0 = no evidence of infection, 1. = outpatient, with no activities limitation; 2. = outpatient, with activities limitation; 3. = hospitalised with no oxygen therapy required; 4. = oxygen therapy employing a mask; 5. = non-invasive ventilation or high flow oxygen; 6. = Mechanical ventilation; 7. = mechanical ventilation and organ support (vasopressors, extracorporeal membrane oxygenation (ECMO), renal replacement therapy (RRT); 8. = Death
次要结局
- Pharmacokinetics evaluation of INM005(1 week)
- Disease progression(up to 2 weeks)
- Mechanical ventilation assistance (MVA)(up to 4 weeks)
- Time to progression of disease(4 weeks)
- Discharge(up to 4 weeks)
- Intensive care unit (ICU) hospitalization(up to 4 weeks)
- Mortality(up to 4 weeks)
- Changes in viral load(up to 3 weeks)
- Mortality at Day 28(up to 4 weeks)
- Pharmacokinetics (PK) Evaluation of INM005 (Cmax)(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose)
- Pharmacokinetics (PK) Evaluation of INM005 (Clearance)(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose)
- Participants Who Require Mechanical Ventilation Assistance (MVA)(up to 4 weeks)
- Pharmacokinetics (PK) Evaluation of INM005 (Weight-adjusted Clearance)(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose)
- Pharmacokinetics (PK) Evaluation of INM005 (AUC0)(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose)
- Pharmacokinetics (PK) Evaluation of INM005 (Elimination Half-time)(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose)
- Pharmacokinetics (PK) Evaluation of INM005 (Elimination Rate)(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose)
- Pharmacokinetics (PK) Evaluation of INM005 (Distribution Volume)(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose)
- Pharmacokinetics (PK) Evaluation of INM005 (Weight-adjusted Distribution Volumen)(0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose)
- Time to Progression of Disease(28 days)
- Clinical Improvement at Day 7 and Day 14(up to 2 weeks)
- Patients Discharged at 28 Days(up to 4 weeks)
- Participants Who Require (ICU) Hospitalization(up to 4 weeks)
- Changes in Viral Load(up to 3 weeks)