Back to resultsInpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC)
Primary Purpose
COVID, COVID-19, SARS-CoV-2
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)
Placebo
Remdesivir
Sponsored by
About this trial
This is an interventional treatment trial for COVID
Eligibility Criteria
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:
- Invasive ventilation
- Non-invasive ventilation
- Extracorporeal membrane oxygenation
- Mechanical circulatory support
- 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:
- Acute coronary syndromes, cerebrovascular syndromes and pulmonary or deep venous thrombosis within 28 days of randomization
- 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
Sites / Locations
- Penrose Hospital
- St. Francis Health Services
- St. Anthony Hospital
- Saint Anthony North Health Campus
- Washington VA Medical Center
- Redmond Regional Medical Center
- National Institutes of Health Clinical Center
- University of Massachusetts
- Hennepin Healthcare Research Institute/HCMC
- University of Missouri
- Cox Medical Centers
- FirstHealth Moore Regional Hospital
- Ohio Health Research Institute
- Hendrick Medical Center
- CHRISTUS Spohn Shoreline Hospital
- University of Texas Southwestern Medical Center
- CJW Chippenham Medical Center
- Henrico Doctors' Hospital (HCA)
- Aarhus Universitetshospital, Skejby
- Bispebjerg Hospital
- CHIP, Department of Infectious Diseases, Section 2100
- Herlev-Gentofte Hospital
- Nordsjællands Hospital, Hillerød
- Hvidovre University Hospital, Department of Infectious Diseases
- Kolding Sygehus
- Odense University Hospital
- Democritus University of Thrace
- 3rd Dept of Medicine, Medical School, NKUA
- 1st Respiratory Medicine Dept, Athens University Medical School
- Attikon University General Hospital
- Dept. of Critical Care & Pulmonary Medicine, Evangelismos General Hospital
- NCGM
- Fujita Health University Hospital
- Institute of Human Virology-Nigeria (IHVN)
- Hospital Universitari Germans Trias i Pujol
- Hospital Universitari Vall d'Hebron
- Hospital del Mar
- Hospital Clínic de Barcelona
- Royal Free Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Intervention Group
Control Group
Arm Description
Participants in this group will receive the investigational product and standard of care (SOC).
Participants in this group will receive a placebo and standard of care (SOC).
Outcomes
Primary Outcome Measures
Ordinal Outcome Scale - Day 7
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
Number of participants with death, SAE or Grade 3 or 4 event through Day 7
Secondary Outcome Measures
N Reaching 3 Least Favorable Categories
N Reaching 3 least favorable categories of ordinal outcome (Categories 5, 6, 7: life-threatening end organ dysfunction, end organ failure, or death)
N Reaching 2 Most Favorable Categories
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
N discharged from hospital or reaching most favorable ordinal category (category 1: not requiring oxygen and no limiting symptoms due to COVID-19)
Full Information
NCT ID
NCT04546581
First Posted
September 8, 2020
Last Updated
March 31, 2022
Sponsor
University of Minnesota
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
1. Study Identification
Unique Protocol Identification Number
NCT04546581
Brief Title
Inpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC)
Official Title
An International Multicenter, Adaptive, Randomized Double-Blind, Placebo-Controlled Trial of the Safety, Tolerability and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Hospitalized Patients at Onset of Clinical Progression of COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
October 8, 2020 (Actual)
Primary Completion Date
May 21, 2021 (Actual)
Study Completion Date
May 21, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID, COVID-19, SARS-CoV-2, SARS (Severe Acute Respiratory Syndrome)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
593 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intervention Group
Arm Type
Experimental
Arm Description
Participants in this group will receive the investigational product and standard of care (SOC).
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
Participants in this group will receive a placebo and standard of care (SOC).
Intervention Type
Biological
Intervention Name(s)
Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Participants will receive a single infusion of the placebo (saline).
Intervention Type
Drug
Intervention Name(s)
Remdesivir
Intervention Description
Remdesivir will be given to participants in both groups as standard of care (SOC).
Primary Outcome Measure Information:
Title
Ordinal Outcome Scale - Day 7
Description
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
Time Frame
7 days
Title
Primary Safety Outcome - Death, SAE or Grade 3 or 4 Events Through Day 7
Description
Number of participants with death, SAE or Grade 3 or 4 event through Day 7
Time Frame
Through Day 7
Secondary Outcome Measure Information:
Title
N Reaching 3 Least Favorable Categories
Description
N Reaching 3 least favorable categories of ordinal outcome (Categories 5, 6, 7: life-threatening end organ dysfunction, end organ failure, or death)
Time Frame
All of follow-up (through Day 28)
Title
N Reaching 2 Most Favorable Categories
Description
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)
Time Frame
All of follow-up (through Day 28)
Title
N Discharged or in Most Favorable Category
Description
N discharged from hospital or reaching most favorable ordinal category (category 1: not requiring oxygen and no limiting symptoms due to COVID-19)
Time Frame
All of follow-up (through Day 28)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Invasive ventilation
Non-invasive ventilation
Extracorporeal membrane oxygenation
Mechanical circulatory support
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:
Acute coronary syndromes, cerebrovascular syndromes and pulmonary or deep venous thrombosis within 28 days of randomization
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Neaton, PhD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark Polizzotto, MD
Organizational Affiliation
The Kirby Institute, University of New South Wales
Official's Role
Study Chair
Facility Information:
Facility Name
Penrose Hospital
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
St. Francis Health Services
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
St. Anthony Hospital
City
Lakewood
State/Province
Colorado
ZIP/Postal Code
80228
Country
United States
Facility Name
Saint Anthony North Health Campus
City
Westminster
State/Province
Colorado
ZIP/Postal Code
80023
Country
United States
Facility Name
Washington VA Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20422
Country
United States
Facility Name
Redmond Regional Medical Center
City
Rome
State/Province
Georgia
ZIP/Postal Code
30165
Country
United States
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
University of Massachusetts
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01665
Country
United States
Facility Name
Hennepin Healthcare Research Institute/HCMC
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55415
Country
United States
Facility Name
University of Missouri
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Cox Medical Centers
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65807
Country
United States
Facility Name
FirstHealth Moore Regional Hospital
City
Pinehurst
State/Province
North Carolina
ZIP/Postal Code
28394
Country
United States
Facility Name
Ohio Health Research Institute
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43215
Country
United States
Facility Name
Hendrick Medical Center
City
Abilene
State/Province
Texas
ZIP/Postal Code
79601
Country
United States
Facility Name
CHRISTUS Spohn Shoreline Hospital
City
Corpus Christi
State/Province
Texas
ZIP/Postal Code
78404
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
CJW Chippenham Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23225
Country
United States
Facility Name
Henrico Doctors' Hospital (HCA)
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23229
Country
United States
Facility Name
Aarhus Universitetshospital, Skejby
City
Aarhus
Country
Denmark
Facility Name
Bispebjerg Hospital
City
Copenhagen
Country
Denmark
Facility Name
CHIP, Department of Infectious Diseases, Section 2100
City
Copenhagen
Country
Denmark
Facility Name
Herlev-Gentofte Hospital
City
Hellerup
Country
Denmark
Facility Name
Nordsjællands Hospital, Hillerød
City
Hillerød
ZIP/Postal Code
3400
Country
Denmark
Facility Name
Hvidovre University Hospital, Department of Infectious Diseases
City
Hvidovre
Country
Denmark
Facility Name
Kolding Sygehus
City
Kolding
Country
Denmark
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Facility Name
Democritus University of Thrace
City
Alexandroupoli
State/Province
Thrace
ZIP/Postal Code
68131
Country
Greece
Facility Name
3rd Dept of Medicine, Medical School, NKUA
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
1st Respiratory Medicine Dept, Athens University Medical School
City
Athens
Country
Greece
Facility Name
Attikon University General Hospital
City
Athens
Country
Greece
Facility Name
Dept. of Critical Care & Pulmonary Medicine, Evangelismos General Hospital
City
Athens
Country
Greece
Facility Name
NCGM
City
Tokyo
Country
Japan
Facility Name
Fujita Health University Hospital
City
Toyoake
Country
Japan
Facility Name
Institute of Human Virology-Nigeria (IHVN)
City
Abuja
Country
Nigeria
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08002
Country
Spain
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Royal Free Hospital
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
A public data set will be made available at the end of the trial
Citations:
PubMed Identifier
36216961
Citation
Jha A, Barker D, Lew J, Manoharan V, van Kessel J, Haupt R, Toth D, Frieman M, Falzarano D, Kodihalli S. Efficacy of COVID-HIGIV in animal models of SARS-CoV-2 infection. Sci Rep. 2022 Oct 10;12(1):16956. doi: 10.1038/s41598-022-21223-2.
Results Reference
derived
PubMed Identifier
35093205
Citation
ITAC (INSIGHT 013) Study Group. Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial. Lancet. 2022 Feb 5;399(10324):530-540. doi: 10.1016/S0140-6736(22)00101-5. Epub 2022 Jan 28.
Results Reference
derived
PubMed Identifier
33715160
Citation
Vandeberg P, Cruz M, Diez JM, Merritt WK, Santos B, Trukawinski S, Wellhouse A, Jose M, Willis T. Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma. Transfusion. 2021 Jun;61(6):1705-1709. doi: 10.1111/trf.16378. Epub 2021 Mar 22.
Results Reference
derived
Learn more about this trial
Inpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC)
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