Convalescent Plasma Therapy - Zurich Protocol (CPT-ZHP)

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

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

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Convalescent plasma

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of CPT applied to COVID-19 patients	Absence of clinical signs of Transfusion Related Lung Inflammation (TRALI) and/or allergic reactions and/or Transfusion Associated Circulatory Overload (TACO)	clinical observation up to 48 hours after the last dose of plasma
Safety of CPT applied to COVID-19 patients	Absence of laboratory signs of haemolytic reactions	1 week (laboratory monitoring up to 7 days after the last administration of plasma)
Improvement of respiratory frequency	Respiratory frequency will be measured at each study visit	3 weeks after the last administration of plasma
Improvement of O2-saturation	O2-Saturation will be measured at each study visit	3 weeks after the last administration of plasma
Improvement of Inflammatory markers (C Reactive Protein, CRP)	CRP will be measured at each study visit	3 weeks after the last administration of plasma
Improvement of Inflammatory markers (Ferritin)	Ferritin will be measured at each study visit	3 weeks after the last administration of plasma
Improvement of Inflammatory markers (IL-6)	IL-6 will be measured at each study visit	3 weeks after the last administration of plasma
Improvement of coagulation-markers (D-dimer)	D-Dimer will be measured at each study visit	3 weeks after the last administration of plasma
Improvement of coagulation-markers (Fibrinogen)	Fibrinogen will be measured at each study visit	3 weeks after the last administration of plasma
Improvement of coagulation-markers (LDH)	LDH will be measured at each study visit	3 weeks after the last administration of plasma
Prevention of ICU-admission	clinical conditions will be assessed throughout the study	3 weeks after the last administration of plasma

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Study Chair: Markus Manz, Professor, University of Zurich

Publications and helpful links

General Publications

• Marconato M, Abela IA, Hauser A, Schwarzmuller M, Katzensteiner R, Braun DL, Epp S, Audige A, Weber J, Rusert P, Schindler E, Pasin C, West E, Boni J, Kufner V, Huber M, Zaheri M, Schmutz S, Frey BM, Kouyos RD, Gunthard HF, Manz MG, Trkola A. Antibodies from convalescent plasma promote SARS-CoV-2 clearance in individuals with and without endogenous antibody response. J Clin Invest. 2022 Jun 15;132(12):e158190. doi: 10.1172/JCI158190.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2020
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: April 8, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 2020-00787

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No