A Phase i, Open-label, Single-centre Clinical Study to Evaluate Safety and Efficacy of Passive Immunization of High-risk SARS-CoV-2 Positive Patients With Convalescent Plasma Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Improvement of O2-saturation
研究概览
简要总结
This is an open-label, single-center, phase I study to assess the safety and efficacy of convalescent plasma therapy (CPT) obtained from donors who were tested positive for SARS-CoV-2 and fully recovered from the infection and administered to patients who are infected with the new coronavirus and present dyspnea or a poor prognosis
详细描述
The outbreak of a new highly contagious and life-threatening infective disease was first reported in China in December 2019. Regardless of the undertaken containing measures, its spreading could not be effectively stopped and currently we are confronting the pandemic diffusion of a newly identified Coronavirus (SARS-CoV-2) (1). This causes a systemic disease, known as (Coronavirus Disease-19) COVID-19, characterised by a broad spectrum of clinical manifestations, including ineffective hyper-inflammation and severe pneumonia, with provisional epidemiologic data indicating a mortality rate of 0.1-15% (2). Do to the lack of vaccination, specific anti-virus sera or monoclonal antibodies, the therapeutic efforts to limit COVID-19 mostly rely on the empirical use of anti-viral drugs. Therefore, being the option of an active immunisation not available and because of the controversial efficacy of the available anti-viral therapies (3), we suggest the option of a passive immunisation for those patients who are infected with the new coronavirus and present dyspnea or a poor prognosis. The use of convalescent plasma, i.e. plasma obtained from donors who were tested positive for SARS-CoV-2 and fully recovered from the infection, could provide a rapid protection, limiting the observed evolution of COVID-19 towards life-threating manifestations (7-9).
When carried on according to standardised measures, the transfusion of plasma is highly safe (10-11) and we assume that products containing anti- SARS-CoV- 2 antibodies will provide the recipients a passive immunity through different mechanisms, including viral neutralisation, antibody-dependent cellular cytotoxicity and/or phagocytosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A) Proven Sars-CoV-2 by PCR and hospitalization for COVID-19 in combination with either (1) or (2):
- •AND (at least one):
- •Pre-existing cardiovascular disease
- •Diabetic disease
- •Immunodeficiency/immunosuppression
- •Neoplastic disease
- •COPD or chronic liver disease or chronic renal failure
- •AND (at least one):
- •SpO2 ≤ 94% on room air or requiring supplemental oxygen at screening
- •Typical changes on chest x-ray and/or lung-CT scan
- •Immunosuppression or neoplastic disease
- •B) Informed Consent as documented by signature (Appendix Informed Consent Form) of the patient or, in case of inability, of the next relative/care-taking person. In the latter case, an independent doctor will also be involved and her/his signature will be required in order to enrol the patient.
排除标准
- •Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product (FFP)
- •Known IgA deficiency
- •Cytokine Release Syndrome grade ≥3 (see score)*
- •Patients already hospitalized in intensive care unit and/or already receiving mechanical ventilation
- •Known or suspected non-compliance, drug or alcohol abuse
- •Previous enrolment into the current study
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
- •Women who are pregnant or breast feeding
- •Intention to become pregnant during the course of the study
- •Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Please note that female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential
结局指标
主要结局
Improvement of O2-saturation
时间窗: 3 weeks after the last administration of plasma
O2-Saturation will be measured at each study visit
Improvement of Inflammatory markers (C Reactive Protein, CRP)
时间窗: 3 weeks after the last administration of plasma
CRP will be measured at each study visit
Improvement of Inflammatory markers (Ferritin)
时间窗: 3 weeks after the last administration of plasma
Ferritin will be measured at each study visit
Improvement of Inflammatory markers (IL-6)
时间窗: 3 weeks after the last administration of plasma
IL-6 will be measured at each study visit
Improvement of coagulation-markers (D-dimer)
时间窗: 3 weeks after the last administration of plasma
D-Dimer will be measured at each study visit
Improvement of coagulation-markers (Fibrinogen)
时间窗: 3 weeks after the last administration of plasma
Fibrinogen will be measured at each study visit
Safety of CPT applied to COVID-19 patients
时间窗: 1 week (laboratory monitoring up to 7 days after the last administration of plasma)
Absence of laboratory signs of haemolytic reactions
Improvement of respiratory frequency
时间窗: 3 weeks after the last administration of plasma
Respiratory frequency will be measured at each study visit
Improvement of coagulation-markers (LDH)
时间窗: 3 weeks after the last administration of plasma
LDH will be measured at each study visit
Prevention of ICU-admission
时间窗: 3 weeks after the last administration of plasma
clinical conditions will be assessed throughout the study
次要结局
- Characterisation of the dynamic of humoral response after therapy(10 Weeks)
- Characterisation of virus reaction to plasma Therapy(10 Weeks)
- Better characterize the the in-vivo anti-virus humoral response against SARS-CoV-2.(10 Weeks)