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

NCT ID: NCT04546581

Last Updated: 2022-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 593 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-08
• Study Completion Date: 2021-05-21

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intervention Group

Participants in this group will receive the investigational product and standard of care (SOC).

Group Type: EXPERIMENTAL

Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)

Intervention Type: BIOLOGICAL

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.

Remdesivir

Intervention Type: DRUG

Remdesivir will be given to participants in both groups as standard of care (SOC).

Control Group

Participants in this group will receive a placebo and standard of care (SOC).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Participants will receive a single infusion of the placebo (saline).

Remdesivir

Intervention Type: DRUG

Remdesivir will be given to participants in both groups as standard of care (SOC).

Interventions

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.

Intervention Type: BIOLOGICAL

Placebo

Participants will receive a single infusion of the placebo (saline).

Intervention Type: OTHER

Remdesivir

Remdesivir will be given to participants in both groups as standard of care (SOC).

Intervention Type: DRUG

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:

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)

NETWORK

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Neaton, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Mark Polizzotto, MD

Role: STUDY_CHAIR

Kirby Institute

Locations

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 D.C., 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

Countries

United States; Denmark; Greece; Japan; Nigeria; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36216961 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35093205 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33715160 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

INSIGHT 013

Identifier Type: -

Identifier Source: org_study_id