Clinical trial NCT04869072: Convalescent Plasma Therapy - Zurich Protocol
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2021-05-03
Enrollment: 30
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label, single-center, phase I study to assess the safety and efficacy of convalescent plasma therapy (CPT).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety of CPT applied to COVID-19 patients
timeFrame: clinical observation up to 48 hours after the last dose of plasma
measure: Safety of CPT applied to COVID-19 patients
timeFrame: 1 week (laboratory monitoring up to 7 days after the last administration of plasma)
measure: Improvement of respiratory frequency
timeFrame: 3 weeks after the last administration of plasma
measure: Improvement of O2-saturation
timeFrame: 3 weeks after the last administration of plasma
measure: Improvement of Inflammatory markers (C Reactive Protein, CRP)
timeFrame: 3 weeks after the last administration of plasma
measure: Improvement of Inflammatory markers (Ferritin)
timeFrame: 3 weeks after the last administration of plasma
measure: Improvement of Inflammatory markers (IL-6)
timeFrame: 3 weeks after the last administration of plasma
measure: Improvement of coagulation-markers (D-dimer)
timeFrame: 3 weeks after the last administration of plasma
measure: Improvement of coagulation-markers (Fibrinogen)
timeFrame: 3 weeks after the last administration of plasma
measure: Improvement of coagulation-markers (LDH)
timeFrame: 3 weeks after the last administration of plasma
measure: Prevention of ICU-admission
timeFrame: 3 weeks after the last administration of plasma
Secondary outcomes:
measure: Characterisation of virus reaction to plasma Therapy
timeFrame: 10 Weeks
measure: Characterisation of the dynamic of humoral response after therapy
timeFrame: 10 Weeks
measure: Better characterize the the in-vivo anti-virus humoral response against SARS-CoV-2.
timeFrame: 10 Weeks
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University of Zurich
name: Markus Manz, Professor
role: STUDY_CHAIR
References:
citation: 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.