Convalescent Plasma Therapy - Zurich Protocol

Phase 1

Completed

• Conditions: COVID-19

• Registration Number: NCT04869072
• Lead Sponsor: University of Zurich

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2020-04-29
• Primary Completion: 2020-11-30
• Study Completion: 2021-03-30
• Status Verified: 2021-04
• Study First Submitted: 2021-04-08
• Study First Submitted QC: 2021-04-27
• Last Update Submitted: 2021-04-27
• Study First Posted: 2021-05-03
• Last Update Posted: 2021-05-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

A) Proven Sars-CoV-2 by PCR and hospitalization for COVID-19 in combination with either (1) or (2):

1. Age ≥50

   AND (at least one):

   • Pre-existing cardiovascular disease
   • Diabetic disease
   • Immunodeficiency/immunosuppression
   • Neoplastic disease
   • COPD or chronic liver disease or chronic renal failure

2. Age ≥18

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.

Exclusion Criteria

1. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product (FFP)
2. Known IgA deficiency
3. Cytokine Release Syndrome grade ≥3 (see score)*
4. ARDS
5. Patients already hospitalized in intensive care unit and/or already receiving mechanical ventilation
6. Known or suspected non-compliance, drug or alcohol abuse
7. Previous enrolment into the current study
8. Enrolment of the investigator, his/her family members, employees and other dependent persons
9. Women who are pregnant or breast feeding
10. Intention to become pregnant during the course of the study
11. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Improvement of O2-saturation	3 weeks after the last administration of plasma	O2-Saturation will be measured at each study visit
Improvement of Inflammatory markers (IL-6)	3 weeks after the last administration of plasma	IL-6 will be measured at each study visit
Improvement of coagulation-markers (D-dimer)	3 weeks after the last administration of plasma	D-Dimer will be measured at each study visit
Improvement of Inflammatory markers (C Reactive Protein, CRP)	3 weeks after the last administration of plasma	CRP will be measured at each study visit
Improvement of Inflammatory markers (Ferritin)	3 weeks after the last administration of plasma	Ferritin will be measured at each study visit
Improvement of coagulation-markers (Fibrinogen)	3 weeks after the last administration of plasma	Fibrinogen will be measured at each study visit
Safety of CPT applied to COVID-19 patients	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	3 weeks after the last administration of plasma	Respiratory frequency will be measured at each study visit
Improvement of coagulation-markers (LDH)	3 weeks after the last administration of plasma	LDH will be measured at each study visit
Prevention of ICU-admission	3 weeks after the last administration of plasma	clinical conditions will be assessed throughout the study

Secondary Outcome Measures

Name	Time	Method
Characterisation of the dynamic of humoral response after therapy	10 Weeks	Measurement of antibody-titres after plasma therapy
Characterisation of virus reaction to plasma Therapy	10 Weeks	Measurement of viral load after plasma therapy
Better characterize the the in-vivo anti-virus humoral response against SARS-CoV-2.	10 Weeks	Performance of neutralisation assay after administration of plasma

Trial Locations

Locations (1)

University Hospital Zurich; 🇨🇭 Zürich, Switzerland