This protocol will serve as a platform for assessing treatments for adult patients hospitalized for medical management of COVID-19 without related serious end-organ failure. Trials will involve sites around the world strategically chosen to ensure rapid enrollment. This trial will compare hyperimmune intravenous immunoglobulin (hIVIG) with matched placebo, when added to standard of care (SOC), for preventing further disease progression and mortality related to COVID-19. SOC will include remdesivir unless it is contraindicated for an individual patient.
The primary endpoint of this trial in hospitalized patients is an ordinal outcome based on
the patient's clinical status on Day 7. It includes 7 mutually exclusive categories capturing
the range of organ dysfunction that may be associated with progression of COVID-19, such as
respiratory dysfunction and coagulation-related complications. The ordinal endpoint is
defined as follows:
7. Death
6. End-organ failure
5. Life-threatening end-organ dysfunction
4. Serious end-organ dysfunction
3. Moderate end-organ dysfunction
2. Limiting symptoms due to COVID-19
1. No limiting symptoms due to COVID-19
Secondary endpoints include time to the 3 least favorable categories, time to the 2 most
favorable categories, and the pulmonary only and thrombotic only components of the primary
ordinal outcome. Mortality, adverse events (AEs), including infusion reactions, and
biological correlates of therapeutic activity are also assessed. Because there is no
established endpoint for evaluating the clinical efficacy of treatments for COVID-19, other
clinically relevant outcomes, including outcomes used in other COVID-19 treatment trials,
will be recorded. Thus, the randomized groups (hIVIG + SOC versus placebo + SOC ) can be
compared for multiple outcomes, and results can be compared or combined with other trials.
Participants will be randomized (1:1) to a single infusion of hIVIG + SOC or placebo + SOC on
the day of randomization (Day 0). Participants taking remdesivir prior to randomization may
be enrolled if eligibility criteria are met. Randomized participants who were not taking
remdesivir before randomization will start taking remdesivir immediately following the
infusion of hIVIG or placebo unless remdesivir is contraindicated. Participants will be
followed for 28 days and, if the trial goes to completion, the primary analysis will be
completed after all participants are followed for 28 days.
Biological: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)
Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is derived from the plasma of individuals who recover and develop neutralizing antibodies. Participants will receive a single infusion.
Other: Placebo
Participants will receive a single infusion of the placebo (saline).
Drug: Remdesivir
Remdesivir will be given to participants in both groups as standard of care (SOC).
Inclusion Criteria:
- SARS-CoV-2 infection documented by polymerase chain reaction (PCR) or other nucleic
acid test (NAT) within 3 days prior to randomization OR documented by NAT more than 3
days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2
infection
- Symptomatic COVID-19 disease
- Duration of symptoms attributable to COVID-19 ≤ 12 days
- Requiring inpatient hospital medical care for clinical manifestations of COVID-19
(admission for public health or quarantine only is not included)
- Willingness to abstain from participation in other COVID-19 treatment trials until
after study Day 7
- Provision of informed consent by participant or legally authorized representative
Exclusion Criteria:
- Prior receipt of SARS-CoV-2 hIVIG or convalescent plasma from a person who recovered
from COVID-19 at any time
- Prior receipt of standard IVIG (not hyperimmune to SARS-CoV-2) within 45 days
- Current or predicted imminent (within 24 hours) requirement for any of the following:
1. Invasive ventilation
2. Non-invasive ventilation
3. Extracorporeal membrane oxygenation
4. Mechanical circulatory support
5. Continuous vasopressor therapy
- History of allergy to IVIG or plasma products
- History of selective IgA deficiency with documented presence of anti-IgA antibodies
- Any medical conditions for which receipt of the required volume of intravenous fluid
may be dangerous to the patient (includes New York Association Class III or IV stage
heart failure)
- Any of the following thrombotic or procoagulant disorders:
1. Acute coronary syndromes, cerebrovascular syndromes and pulmonary or deep venous
thrombosis within 28 days of randomization
2. History of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations,
antithrombin III deficiency, protein C deficiency, protein S deficiency or
antiphospholipid syndrome
- Any condition for which, in the opinion of the investigator, participation would not
be in the best interest of the subject or that could prevent, limit, or confound the
protocol-specified assessments
Penrose Hospital
Colorado Springs, Colorado, United States
St. Francis Health Services
Colorado Springs, Colorado, United States
St. Anthony Hospital
Lakewood, Colorado, United States
Saint Anthony North Health Campus
Westminster, Colorado, United States
Washington VA Medical Center
Washington, District of Columbia, United States
Redmond Regional Medical Center
Rome, Georgia, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
University of Massachusetts
Worcester, Massachusetts, United States
Hennepin Healthcare Research Institute/HCMC
Minneapolis, Minnesota, United States
University of Missouri
Columbia, Missouri, United States
Cox Medical Centers
Springfield, Missouri, United States
FirstHealth Moore Regional Hospital
Pinehurst, North Carolina, United States
Ohio Health Research Institute
Columbus, Ohio, United States
Hendrick Medical Center
Abilene, Texas, United States
CHRISTUS Spohn Shoreline Hospital
Corpus Christi, Texas, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
CJW Chippenham Medical Center
Richmond, Virginia, United States
Henrico Doctors' Hospital (HCA)
Richmond, Virginia, United States
Aarhus Universitetshospital, Skejby
Aarhus, Denmark
Bispebjerg Hospital
Copenhagen, Denmark
CHIP, Department of Infectious Diseases, Section 2100
Copenhagen, Denmark
Herlev-Gentofte Hospital
Hellerup, Denmark
Nordsjællands Hospital, Hillerød
Hillerød, Denmark
Hvidovre University Hospital, Department of Infectious Diseases
Hvidovre, Denmark
Kolding Sygehus
Kolding, Denmark
Odense University Hospital
Odense, Denmark
Democritus University of Thrace
Alexandroupoli, Thrace, Greece
3rd Dept of Medicine, Medical School, NKUA
Athens, Greece
1st Respiratory Medicine Dept, Athens University Medical School
Athens, Greece
Attikon University General Hospital
Athens, Greece
Dept. of Critical Care & Pulmonary Medicine, Evangelismos General Hospital
Athens, Greece
NCGM
Tokyo, Japan
Fujita Health University Hospital
Toyoake, Japan
Institute of Human Virology-Nigeria (IHVN)
Abuja, Nigeria
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital Universitari Vall d'Hebron
Barcelona, Catalonia, Spain
Hospital del Mar
Barcelona, Spain
Hospital Clínic de Barcelona
Barcelona, Spain
Royal Free Hospital
London, United Kingdom