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

NCT04384497 | Completed Phase 1 DMC

• 1 other identifier: CP2
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

COVID-19

Keywords

COVID-19 convalescent plasma treatment; SARS-CoV-2 infection; Dosing; Safety; Effectiveness

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Adverse events

  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

  28 days

• Clearance of viremia

  6 months.

• Fever and symptoms

  Until discharged from the hospital, up to 2 months

• Inflammatory parameters

  Until discharged from the hospital, up to 2 months

Study Arms (1)

Convalescent plasma treatment

EXPERIMENTAL

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

Interventions

SARS-CoV-2 convalescent plasma BIOLOGICAL

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.

Convalescent plasma treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Written informed consent after meeting with a study physician and ability and willingness to complete follow up

You may not qualify if:

• 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

Sponsors & Collaborators

• Joakim Dillner: lead
• Danderyd Hospital: collaborator
• Karolinska University Hospital: collaborator
• Karolinska Institutet: collaborator

Study Sites (2)

Danderyd Hospital

Danderyd, Stockholm County, 18257, Sweden

Location

Karolinska University Hospital

Stockholm, 14186, Sweden

Location

MeSH Terms

Conditions

COVID-19

Interventions

COVID-19 Serotherapy

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Johan Ursing, MD, PhD

  Danderyd Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Infectious Disease Epidemiology; Director of R&D

Model Details: An open, non-randomised controlled, safety and dose identifying clinical trial

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 12, 2020
• Study Start: May 7, 2020
• Primary Completion: June 1, 2020
• Study Completion: December 1, 2020
• Last Updated: December 3, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

SE (2)