Inpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC)

Phase 3

Completed

Conditions: COVID
COVID-19
SARS-CoV-2
SARS (Severe Acute Respiratory Syndrome)

Interventions: Biological: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)
Other: Placebo
Drug: Remdesivir

Registration Number: NCT04546581

Lead Sponsor: University of Minnesota

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 593

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention Group	Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)	Participants in this group will receive the investigational product and standard of care (SOC).
Control Group	Placebo	Participants in this group will receive a placebo and standard of care (SOC).
Control Group	Remdesivir	Participants in this group will receive a placebo and standard of care (SOC).
Intervention Group	Remdesivir	Participants in this group will receive the investigational product and standard of care (SOC).

Primary Outcome Measures

Name	Time	Method
Ordinal Outcome Scale - Day 7	7 days	The primary objective is to compare the clinical status of patients in each group on day 7 of follow-up using the primary ordinal outcome with 7 mutually exclusive categories: 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 Outcome is reported as the percent of participants in each of 7 categories. Primary 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. Minimum value = 1, Maximum value = 7 Higher scores mean a worse outcome
Primary Safety Outcome - Death, SAE or Grade 3 or 4 Events Through Day 7	Through Day 7	Number of participants with death, SAE or Grade 3 or 4 event through Day 7

Secondary Outcome Measures

Name	Time	Method
N Reaching 2 Most Favorable Categories	All of follow-up (through Day 28)	N Reaching 2 most favorable categories of ordinal outcome (Categories 1 and 2: not requiring oxygen with or without limiting symptoms due to COVID-19)
N Discharged or in Most Favorable Category	All of follow-up (through Day 28)	N discharged from hospital or reaching most favorable ordinal category (category 1: not requiring oxygen and no limiting symptoms due to COVID-19)
N Reaching 3 Least Favorable Categories	All of follow-up (through Day 28)	N Reaching 3 least favorable categories of ordinal outcome (Categories 5, 6, 7: life-threatening end organ dysfunction, end organ failure, or death)

Trial Locations

Locations (39): CHRISTUS Spohn Shoreline Hospital
🇺🇸
Corpus Christi, Texas, United States
Royal Free Hospital
🇬🇧
London, United Kingdom
3rd Dept of Medicine, Medical School, NKUA
🇬🇷
Athens, Greece
Hospital del Mar
🇪🇸
Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Catalonia, Spain
1st Respiratory Medicine Dept, Athens University Medical School
🇬🇷
Athens, Greece
Democritus University of Thrace
🇬🇷
Alexandroupoli, Thrace, Greece
Hospital Clínic de Barcelona
🇪🇸
Barcelona, Spain
Penrose Hospital
🇺🇸
Colorado Springs, Colorado, United States
St. Francis Health Services
🇺🇸
Colorado Springs, Colorado, United States
Saint Anthony North Health Campus
🇺🇸
Westminster, Colorado, 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
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
Bispebjerg Hospital
🇩🇰
Copenhagen, Denmark
CHIP, Department of Infectious Diseases, Section 2100
🇩🇰
Copenhagen, Denmark
Nordsjællands Hospital, Hillerød
🇩🇰
Hillerød, Denmark
Herlev-Gentofte Hospital
🇩🇰
Hellerup, Denmark
Hvidovre University Hospital, Department of Infectious Diseases
🇩🇰
Hvidovre, Denmark
Aarhus Universitetshospital, Skejby
🇩🇰
Aarhus, Denmark
Kolding Sygehus
🇩🇰
Kolding, Denmark
Odense University Hospital
🇩🇰
Odense, Denmark
Hospital Universitari Germans Trias i Pujol
🇪🇸
Badalona, Barcelona, Spain
Institute of Human Virology-Nigeria (IHVN)
🇳🇬
Abuja, Nigeria
Dept. of Critical Care & Pulmonary Medicine, Evangelismos General Hospital
🇬🇷
Athens, Greece
NCGM
🇯🇵
Tokyo, Japan
Washington VA Medical Center
🇺🇸
Washington, District of Columbia, United States
Attikon University General Hospital
🇬🇷
Athens, Greece
Fujita Health University Hospital
🇯🇵
Toyoake, Japan
St. Anthony Hospital
🇺🇸
Lakewood, Colorado, United States