Phase I/II Clinical Trial for Dose Escalation and Safety Assessment and Clinical Response of Anti-SARS-CoV-2 Serum Produced by Instituto Butantan
试验速览
- 阶段
- 1 期
- 入组人数
- 618
- 试验地点
- 4
- 主要终点
- Frequency of local and systemic adverse events
研究概览
简要总结
Phase I/II Randomized Clinical Trial to evaluate the safety, pharmacokinetic and efficacy of Anti-SARS-CoV-2 hyperimmune serum.
The study will include patients at early stage of COVID-19 with increased risk for severe disease due to underlying medical conditions to determine the utility of an equine heterologous serum anti-SARS-CoV-2 to avoid progression to a severe COVID-19
详细描述
Phase I/II Clinical Trial, randomized, multicentric, on three stages (A, B and C) to evaluate the safety, pharmacokinetic and efficacy of Anti-SARS-CoV-2 serum and dose escalation.
The study will be in three stages:
Stage A: 30 kidney transplanted participants (very high risk), where 15 will received 1 vial (5 mL) and 15 will received 2 vials (10 mL) of serum;
Stage B: 30 immunocompetent participants with at least 2 risk factors for severe disease (high risk) who will receive the dose selected by stage A;
Stage C: 558 participants, of very high risk and high risk, compared with placebo in allocation 2:1 (endpoint-driven design)
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
- Double (Participant, Investigator)
盲法说明
Stage C of this study was designed as double-blind to avoid the bias introduction in the efficacy and adverse events evaluation. The clinical care team, the responsible professional for administering the serum and the participant will not know which product under investigation will be administered. Only the pharmacists or nurses responsible for the randomization of the study, separation and blinding of the product under investigation will have access to unblinded information. The allocation of the product under investigation will only be revealed after the completion of the participants' following up and database closing to guarantee a long-term safety evaluation of the product. The sponsor's operational team will also remain blind.
If necessary, independent scientists not involved with the clinical or laboratory evaluation of the participants, who analyze the unblinded data of laboratory results.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults 18 years of age or older;
- •Diagnosis of SARS-CoV-2 infection confirmed by RT-PCR or antigen test no more than 5 days ago;
- •Onset of clinical signs and symptoms of COVID-19 no more than 5 days manifested as:
- •Presenting sudden onset of anosmia and/or ageusia without any other reasonable explanation and/or;
- •Thoracic image by radiography, tomography or ultrasonography compatible with acute clinical symptoms findings of COVID-19 and/or;
- •Acute onset of cough accompanied by fever and/or
- •Acute onset of three or more of the following symptoms: fever, cough, fatigue or general weakness, headache, myalgia, sore throat, runny nose, dyspnea, anorexia or nausea or vomit, diarrhea and mental status change.
- •Oxygen saturation by pulse oximetry ≥92%
- •Agree to periodic contacts by phone, electronic means and home visits;
- •Demonstrate intention to participate in the study, documented by Informed Consent Form signature on the part of the participant.
- •For the very high risk group:
- •Being on continuous drug immunosuppressant more than two weeks due to a basic medical condition (e.g. transplant or cancer);
- •For the high risk group:
- •To present at least two risk factors for developing serious COVID-19 (Over 60 years of age; diabetes mellitus; chronic obstructive pulmonary disease; kidney disease; cardiovascular diseases and body mass index ≥ 35).
排除标准
- •Presenting COVID-9 in need of oxygen therapy on the moment of study inclusion, in other words, score 5 or higher in WHO COVID-19 progression scale;
- •Behavioral, cognitive or psychiatric disease that, in principal investigator opinion or his/her medical representative, affect the participant capacity in understanding and collaborating with study protocol requirements;
- •Any use considered alcohol or drugs abuse in the last 12 months prior to study inclusion that caused medical, professional or family problems, as indicated by clinical history;
- •Severe allergic reaction history or anaphylaxis to heterologous serum or product components of the study;
- •To have received heterologous serum or convalescent plasma in the last three months before of study inclusion, or planned administration of hemoderivatives or immunoglobulin on the next 28 days of study inclusion;
- •The participant is a team member who is conducting the study or is in a dependent relationship with one of the study team members. Dependency relationships include close relatives (in other words, sons, partner/spouse, brothers, parents), as well as Researcher staff or staff from the location conducting the study;
- •Any other condition that, in the principal investigator opinion or his/her medical representative, could threaten the safety or rights of a potential participant or which prevents him from fulfilling with this protocol.
- •For female:
- •Pregnancy (confirmed by positive β-hCG test), breastfeeding and/or expressing an intention to have sexual practices with reproductive potential without using a contraceptive method within four weeks of the product administration;
- •For stages A and B:
- •Previous immunization with vaccine against COVID-19
结局指标
主要结局
Frequency of local and systemic adverse events
时间窗: 12 hours after product administration
Frequency of local and systemic adverse events, solicited and unsolicited, during the infusion and within 12 hours after administration of the heterologous serum
Proportion of patients with change in COVID-19 disease progression profile after administration of anti-SARS-CoV-2 serum
时间窗: 14 days after product administration
Proportion of patients with change in COVID-19 disease progression profile after administration of anti-SARS-CoV-2 serum, based on the WHO clinical progression scale (not progression to severe disease requiring mechanical ventilation or death - Score 7 or larger)
Anti-SARS-CoV-2 serum average life
时间窗: 28 days after product administration
Anti-SARS-CoV-2 serum average life measured by equine antibodies levels
次要结局
- Clinical response(14 days after product administration)
- Symptoms duration(28 days after product administration)
- Deaths(28 days after product administration)
- Frequency of severe adverse events(28 days after product administration)
- Frequency of local and systemic adverse events(28 days after product administration)
- Hospitalization time in Intensive Care Unit(28 days after product administration)