Convalescent Plasma for Treatment of COVID-19: An Exploratory Dose Identifying Study

Convalescent plasma has been shown to be safe and effective for treatment of several diseases. Preliminary data indicates that it is safe and effective for treatment of COVID. However, data is limited to small studies and case series on severely ill patients.

In a preliminary safety study 10 patients with severe COVID-19, defined as requiring supplementary oxygen, having fever and a duration of illness less than 11 days were treated with 200 ml of CP. CP was given as a slow infusion without obvious adverse events. Eight patients had viremia. One patient rapidly cleared the virus and recovered following CP treatment. CP infusion did not appear to clear viremia in 7/8 patients. Five of these were eventually admitted to ICU. Thus CP did not appear to cause acute toxicity but did not seem to be effective at the dose used. Viremia seemed to be a marker of a high risk of disease progression The proposed study thus aims to treat a high risk population identified by having viremia irrespective of but hopefully before they develop pulmonary injury such that they require supplementary oxygen therapy. Moreover the dose of plasma will be increased incrementally with the aim of clearing viremia as our initial study indicates that continued viremia is driving COVID-19.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: SARS-CoV-2 convalescent plasma

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 14186
    • Karolinska University Hospital
  • Stockholm
    • Danderyd, Stockholm, Sweden, 18257
      • Danderyd Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 or older
• Admitted to a study hospital
• Active COVID-19 defined as symptoms + SARS CoV-2 identified from upper or lower airway samples
• Negative pregnancy test taken before inclusion and use of an acceptable effective method of contraception until treatment discontinuation if the participant is a woman of childbearing potential
• Written informed consent after meeting with a study physician and ability and willingness to complete follow up

Exclusion Criteria:

• No matching plasma donor (Exact matching in both the ABO system is required)
• Unavailability of plasma
• Significant growth of alternative lower airway pathogen such as Streptococcus pneumoniae or Haemophilus influenzae in sputum
• Estimated glomerular filtration rate <60 (kidney failure stage III or more)
• Pregnancy (urinary-hcg)
• Breast feeding
• History of severe allergic reactions to foods or other substances that the donor may have been exposed to (for example severe peanut allergy)
• Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Convalescent plasma treatment; Participants will receive 200 ml convalescent plasma daily until SARS-CoV-2 is no longer detectable in the blood up to a maximum of 7 CP infusions. CP will be given as a slow infusion over 1 hour. Patients will be monitored for adverse events, especially allergic reactions.	Biological: SARS-CoV-2 convalescent plasma; Treatment with convalescent plasma (200ml, up to a maximum of 7 CP infusions). Plasma from consenting individuals who have recovered from SARS-CoV-2 infection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and proportion of patients with progression to ventilation or sustained requirement of supplementary oxygen therapy	Progression to non-invasive or invasive ventilation or a sustained requirement of 15L of supplementary oxygen therapy in patients that are not eligible for intensive care treatment.	Measured in the first 28 days after inclusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse reactions and serious adverse reactions. The safety of the intervention will be assessed with regard to AEs, baseline medical conditions, and findings from the physical examination and laboratory tests. Possible adverse events will be elicited using a modification and Swedish translation (appendix 6) of Common Terminology Criteria for Adverse Events v5.0 and they will be continuously reported to the sponsor. Adverse events related to convalescent plasma therapy shall be followed to assess reversibility.	The reporting period for AEs starts at inclusion and ends at the final follow-up visit 2 months after inclusion.
Dose of plasma needed to clear viremia	Measured as doses of convalescent plasma administered (1-7 infusions, 200ml).	28 days
Clearance of viremia	SARS-CoV-2 RNA detection by PCR in blood or serum. Blood samples for immunological analyses and serology will be taken daily until discharge, on day 28, and at 6 months.	6 months.
Fever and symptoms	Time to resolution of fever and symptoms. Breathing rate, peripheral oxygen saturation (measured with pulse oximetry after 20 minutes of rest), oxygen use, pulse, blood pressure, body temperature and mental state will be monitored 3 times/day while hospitalized.	Until discharged from the hospital, up to 2 months
Inflammatory parameters	Time to normalization of inflammatory parameters. Blood samples for inflammatory parameters will be taken daily until normalized or discharged from the hospital.	Until discharged from the hospital, up to 2 months
Antibody response to SARS-CoV-2	Characterization of the antibody response to SARS-CoV-2. Blood samples for immunological analyses and serology will be taken daily until discharge, on day 28, and at 6 months.	6 months

Collaborators and Investigators

• Sponsor: Joakim Dillner
• Collaborators: Karolinska University Hospital; Karolinska Institutet; Danderyd Hospital
• Investigators: Principal Investigator: Johan Ursing, MD, PhD, Danderyd Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 7, 2020
• Primary Completion (ACTUAL): June 1, 2020
• Study Completion (ACTUAL): December 1, 2020

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 9, 2020
• First Posted (ACTUAL): May 12, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 3, 2021
• Last Update Submitted That Met QC Criteria: December 2, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Effectiveness; SARS-CoV-2 infection; COVID-19 convalescent plasma treatment; Dosing
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CP2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will be sharing the data, but the management plan is being designed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No