Inpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC)
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| ClinicalTrials.gov Identifier: NCT04546581 |
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Recruitment Status :
Completed
First Posted : September 14, 2020
Results First Posted : April 4, 2022
Last Update Posted : April 4, 2022
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| 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 |
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.
| 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 |
|---|---|
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Experimental: Intervention Group
Participants in this group will receive the investigational product and standard of care (SOC).
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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). |
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Placebo Comparator: Control Group
Participants in this group will receive a placebo and standard of care (SOC).
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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). |
- 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
- 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
- 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)
- 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)
- 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)
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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)
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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
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
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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 |
Documents provided by University of Minnesota:
| 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) |
| 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 |
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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 |