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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04546581
Recruitment Status : Completed
First Posted : September 14, 2020
Results First Posted : April 4, 2022
Last Update Posted : April 4, 2022
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health (NIH)
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
COVID COVID-19 SARS-CoV-2 SARS (Severe Acute Respiratory Syndrome) Biological: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) Other: Placebo Drug: Remdesivir Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 593 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : October 8, 2020
Actual Primary Completion Date : May 21, 2021
Actual Study Completion Date : May 21, 2021


Arm Intervention/treatment
Experimental: Intervention Group
Participants in this group will receive the investigational product and standard of care (SOC).
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.

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

Placebo Comparator: Control Group
Participants in this group will receive a placebo and standard of care (SOC).
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).




Primary Outcome Measures :
  1. Ordinal Outcome Scale - Day 7 [ Time Frame: 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


  2. Primary Safety Outcome - Death, SAE or Grade 3 or 4 Events Through Day 7 [ Time Frame: Through Day 7 ]
    Number of participants with death, SAE or Grade 3 or 4 event through Day 7


Secondary Outcome Measures :
  1. N Reaching 3 Least Favorable Categories [ Time Frame: 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)

  2. N Reaching 2 Most Favorable Categories [ Time Frame: 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)

  3. N Discharged or in Most Favorable Category [ Time Frame: 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04546581


Locations
Show Show 39 study locations
Sponsors and Collaborators
University of Minnesota
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health (NIH)
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
Investigators
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Principal Investigator: James Neaton, PhD University of Minnesota
Study Chair: Mark Polizzotto, MD The Kirby Institute, University of New South Wales
  Study Documents (Full-Text)

Documents provided by University of Minnesota:
Study Protocol  [PDF] August 20, 2020
Statistical Analysis Plan  [PDF] March 27, 2021
Informed Consent Form  [PDF] September 14, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT04546581    
Other Study ID Numbers: INSIGHT 013
First Posted: September 14, 2020    Key Record Dates
Results First Posted: April 4, 2022
Last Update Posted: April 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: A public data set will be made available at the end of the trial
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)

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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
Additional relevant MeSH terms:
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COVID-19
Severe Acute Respiratory Syndrome
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Remdesivir
Immunoglobulins
Immunoglobulins, Intravenous
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents