We are investigating Coronavirus disease 2019 (COVID-19) which is predominantly a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MedDRA version: 23.1 Level: PT Classification code 10084460 Term: COVID-19 treatment System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Name: Anti-COVID-19 hIVIG Grifols Therapeutics
Pharmaceutical Form: Infusion
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use
Sponsors
Office of Sponsored Projects,University of Minnesota
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a patient must meet all of the following inclusion criteria prior to randomisation: 1. Clinical risk based on age = 55 years or an adult (age = 18 years) with an immunosuppressed condition. 2. Positive test for SARS-CoV-2 within =5 days (if >1 test, the first positive is within =5 days). Tests may include an institutional-based nucleic acid amplification test (NAAT), or any protocol-approved rapid test. 3. Within =5 days from symptom onset, if symptomatic from current SARS-CoV-2 infection. 4. Agrees to not participate in another clinical trial for the treatment or management of SARS-CoV-2 infection through Day 7, or until hospitalized or significant disease progression if prior to Day 7 (defined by ordinal category 4 or 5). 5. Participant provides written informed consent prior to study procedures, and understands and agrees to adhere to planned study procedures through Day 28. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: An individual who meets any of the following criteria will be excluded from participation: 1. Asymptomatic and had prior symptoms from the current infection that have now resolved (for >24 hours). 2. Asymptomatic and has received a vaccination for COVID-19 (=1 dose). 3. Undergoing evaluation for possible admission to hospital for medical management (this does not include evaluation of possible hospitalization for public health purposes). 4. Evidence of pneumonia and/or hypoxia due to COVID-19 (NOTE: chest imaging is not required, but if available it should not show new infiltrates suggestive of pneumonia; hypoxia is defined by new oxygen supplementation or increase above pre-illness level). 5. Prior receipt of immunoglobulin product or passive immune therapy for SARS-CoV-2 in the past 90 days (i.e., convalescent plasma, SARS-CoV-2 monoclonal antibodies, or any IVIG). 6. Any of the following thrombotic or procoagulant conditions or disorders: • acute coronary syndrome, cerebrovascular syndrome, pulmonary embolism, or deep venous thrombosis within 28 days of randomization. • prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antiphospholipid syndrome, or a deficiency in antithrombin III, protein C, or protein S. 7. History of hypersensitivity to blood, plasma or IVIG excipients. 8. Known IgA deficiency or anti-IgA antibodies. 9.Medical conditions for which receipt of a 300 mL volume of IV fluid from study treatment may pose specific risk to the patient (e.g., decompensated congestive heart failure) 10. In the opinion of the investigator, any condition for which participation would not be in the best interest of the participant or that could prevent or confound protocol assessments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary endpoint of this outpatient trial is a five-category ordinal outcome that assesses the participant’s clinical status seven days after the infusion of hIVIG or placebo. The ordinal scale is as follows: Category 1: Asymptomatic and no limitations in usual activity due to COVID-19 Category 2: Mild COVID-19 illness or minor limitations to usual activity Category 3: Moderate COVID-19 illness and major limitations to usual activity Category 4: Severe COVID-19 or other serious disease manifestation from COVID-19 Category 5: Critical illness from COVID-19 or Death The goals of this study are to assess the safety and efficacy of a single infusion of hIVIG + SOC versus placebo + SOC in preventing further progression related to COVID-19 when administered early after diagnosis and symptom onset (if symptomatic), with a further aim to concurrently assess for more rapid resolution of illness and restoration of health status to the pre-illness state.;Secondary Objective: The clinical status as classified on the ordinal outcome scale will be assessed with a number of additional analyses comparing hIVIG with placebo, among the overall study population as well as for the key subgroup of those not receiving direct-acting anti-SARS-CoV-2 agents or (MAbs) as part of Standard Care (SOC) (i.e., stratum 1), including: 1. All-cause hospitalization or death through 28 days. 2. All-cause mortality through 28 days. 3. Significant disease progression through 28 days, using a time to event analysis with outcome defined by fulfilling criteria for category 4 or 5 on the ordinal scale. 4. Distribution of ordinal scale outcome at Day 4, 14, and 28. 5. The proportion of participants with any disease progression at Day 7, using a sliding dichotomous scale progression defined by a categorisation;Primary end point(s): The primary objective of the Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC) (INSIGHT 012) trial is to compare the safety and efficacy of a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The clinical status as classified on the ordinal outcome scale will be assessed with a number of additional analyses comparing hIVIG (pooled for the 2 hIVIG products) with placebo, among the overall study population as well as for the key subgroup of those not receiving anti-SARS-CoV-2 monoclonal antibodies as part of SOC (stratum 1), including: 1. All-cause hospitalisation or death through 28 days. 2. All-cause mortality through 28 days. 3. Significant disease progression through 28 days, using a time to event analysis with outcome defined by fulfilling criteria for category 4 or 5 on the ordinal scale. 4. Distribution of ordinal scale outcome at Day 4, 14, and 28. 5. The proportion of participants with any disease progression at Day 7, using a sliding dichotomous scale progression defined by a categorization on the ordinal scale that is worse than the status at entry. 6. The proportion of participants who progress to categories 3-5 on the clinical ordinal scale at Day 7 among participants in categories 1 or 2 of the ordinal scale at entry. 7. The severity of progression during follow-up, defined by the worst health status achieved on the clinical ordinal scale at any point by Day 7, 14, and 28. 8. The proportion of participants that attain their pre-COVID health status without limitations in usual activity (i.e., category 1) at Day 7, 14, and 28. 9. Change in quantitative measures of viral burden between Day 0 and Day 7, including serum antigen levels (e.g., nucleocapsid antigen) as well as by polymerase chain reaction (PCR) from nasal and saliva specimens. 10. Change in SARS-CoV-2 antibody levels between Day 0 and Day 7, including subclasses and neutralizing titers. 11. Utilisation of health care resources through 28 days, defined by the proportion of participants that had health care engagement for the purposes of medical evaluation and/or management of COVID-19 illness (e.g., via telehealth, clinic, urgent care, A&E (casualty), or ho | — |
Countries
Argentina, Australia, Denmark, Greece, India, Indonesia, Mexico, Peru, Spain, Thailand, Uganda, United Kingdom, United States
Contacts
Public ContactAlejandro Arenas-Pinto
MRC Clinical Trials Unit at UCL
Outcome results
None listed