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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04546581
• Other study ID #: INSIGHT 013
• Status: Completed
• Phase: Phase 3
• Start date: October 8, 2020
• Est. completion date: May 21, 2021

Study information

• Verified date: March 2022
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 593
• Est. completion date: May 21, 2021
• Est. primary completion date: May 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.

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).

Locations

Country	Name	City	State
Denmark	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
Greece	Democritus University of Thrace	Alexandroupoli	Thrace
Greece	1st Respiratory Medicine Dept, Athens University Medical School	Athens
Greece	3rd Dept of Medicine, Medical School, NKUA	Athens
Greece	Attikon University General Hospital	Athens
Greece	Dept. of Critical Care & Pulmonary Medicine, Evangelismos General Hospital	Athens
Japan	NCGM	Tokyo
Japan	Fujita Health University Hospital	Toyoake
Nigeria	Institute of Human Virology-Nigeria (IHVN)	Abuja
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Catalonia
United Kingdom	Royal Free Hospital	London
United States	Hendrick Medical Center	Abilene	Texas
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	Penrose Hospital	Colorado Springs	Colorado
United States	St. Francis Health Services	Colorado Springs	Colorado
United States	University of Missouri	Columbia	Missouri
United States	Ohio Health Research Institute	Columbus	Ohio
United States	CHRISTUS Spohn Shoreline Hospital	Corpus Christi	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	St. Anthony Hospital	Lakewood	Colorado
United States	Hennepin Healthcare Research Institute/HCMC	Minneapolis	Minnesota
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	CJW Chippenham Medical Center	Richmond	Virginia
United States	Henrico Doctors' Hospital (HCA)	Richmond	Virginia
United States	Redmond Regional Medical Center	Rome	Georgia
United States	Cox Medical Centers	Springfield	Missouri
United States	Washington VA Medical Center	Washington	District of Columbia
United States	Saint Anthony North Health Campus	Westminster	Colorado
United States	University of Massachusetts	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
University of Minnesota	International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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)	All of follow-up (through Day 28)
Secondary	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)	All of follow-up (through Day 28)
Secondary	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)	All of follow-up (through Day 28)