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

NCT04546581 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: INSIGHT 013
• Study Type: interventional
• Target: 593
• Locations: 7 countries
• Sites: 39

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

  7 days

• 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

  Through Day 7

Secondary Outcomes (3)

• N Reaching 3 Least Favorable Categories

  All of follow-up (through Day 28)

• N Reaching 2 Most Favorable Categories

  All of follow-up (through Day 28)

• N Discharged or in Most Favorable Category

  All of follow-up (through Day 28)

Study Arms (2)

Intervention Group

EXPERIMENTAL

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

Biological: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG); Drug: Remdesivir

Control Group

PLACEBO COMPARATOR

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

Other: Placebo; Drug: Remdesivir

Interventions

Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) 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.

Intervention Group

Placebo OTHER

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

Control Group

Remdesivir DRUG

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

Control Group; Intervention Group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institutes of Health (NIH): collaborator
• International Network for Strategic Initiatives in Global HIV Trials (INSIGHT): collaborator

Study Sites (39)

Penrose Hospital

Colorado Springs, Colorado, 80907, United States

Location

St. Francis Health Services

Colorado Springs, Colorado, 80907, United States

Location

St. Anthony Hospital

Lakewood, Colorado, 80228, United States

Location

Saint Anthony North Health Campus

Westminster, Colorado, 80023, United States

Location

Washington VA Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

Redmond Regional Medical Center

Rome, Georgia, 30165, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01665, United States

Location

Hennepin Healthcare Research Institute/HCMC

Minneapolis, Minnesota, 55415, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

Cox Medical Centers

Springfield, Missouri, 65807, United States

Location

FirstHealth Moore Regional Hospital

Pinehurst, North Carolina, 28394, United States

Location

Ohio Health Research Institute

Columbus, Ohio, 43215, United States

Location

Hendrick Medical Center

Abilene, Texas, 79601, United States

Location

CHRISTUS Spohn Shoreline Hospital

Corpus Christi, Texas, 78404, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

CJW Chippenham Medical Center

Richmond, Virginia, 23225, United States

Location

Henrico Doctors' Hospital (HCA)

Richmond, Virginia, 23229, United States

Location

Aarhus Universitetshospital, Skejby

Aarhus, Denmark

Location

Bispebjerg Hospital

Copenhagen, Denmark

Location

CHIP, Department of Infectious Diseases, Section 2100

Copenhagen, Denmark

Location

Herlev-Gentofte Hospital

Hellerup, Denmark

Location

Nordsjællands Hospital, Hillerød

Hillerød, 3400, Denmark

Location

Hvidovre University Hospital, Department of Infectious Diseases

Hvidovre, Denmark

Location

Kolding Sygehus

Kolding, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

Democritus University of Thrace

Alexandroupoli, Thrace, 68131, Greece

Location

3rd Dept of Medicine, Medical School, NKUA

Athens, 11527, Greece

Location

1st Respiratory Medicine Dept, Athens University Medical School

Athens, Greece

Location

Attikon University General Hospital

Athens, Greece

Location

Dept. of Critical Care & Pulmonary Medicine, Evangelismos General Hospital

Athens, Greece

Location

NCGM

Tokyo, Japan

Location

Fujita Health University Hospital

Toyoake, Japan

Location

Institute of Human Virology-Nigeria (IHVN)

Abuja, Nigeria

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital del Mar

Barcelona, 08002, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Royal Free Hospital

London, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 36216961 DERIVED

• 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.

  PMID: 35093205 DERIVED

• 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.

  PMID: 33715160 DERIVED

MeSH Terms

Conditions

COVID-19; Severe Acute Respiratory Syndrome

Interventions

HIV hyperimmune globulin; remdesivir

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

Results Point of Contact

• Title: James Neaton
• Organization: University of Minnesota

neato001@umn.edu

612-626-9040

Study Officials

• James Neaton, PhD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Mark Polizzotto, MD

  Kirby Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 14, 2020
• Study Start: October 8, 2020
• Primary Completion: May 21, 2021
• Study Completion: May 21, 2021
• Last Updated: April 4, 2022
• Results First Posted: April 4, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

DK (8); NG (1); ES (4); JP (2); GB (1); GR (5); US (18)