RecruitingPhase 3NCT04910269

Outpatient Treatment With Anti-Coronavirus Immunoglobulin

An International Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Outpatients in Early Stages of COVID-19


Sponsor

University of Minnesota

Enrollment

820 participants

Start Date

Aug 6, 2021

Study Type

INTERVENTIONAL

Conditions

Summary

The primary objective of the Outpatient Treatment with Anti-Coronavirus Immunoglobulin (OTAC) (INSIGHT 012) trial is to compare the safety and efficacy of a single infusion of anti-COVID-19 hyperimmune intravenous immunoglobulin (hIVIG) versus placebo among adults with recently diagnosed severe acute respiratory syndrome - coronavirus 2 (SARS-CoV2) infection who do not require hospitalization. The primary endpoint of this double-blind randomized trial is a five-category ordinal outcome that assesses the participant's clinical status seven days after the infusion of hIVIG or placebo. 1. Asymptomatic and no limitations in usual activity due to COVID-19 2. Mild COVID-19 illness or minor limitations to usual activity 3. Moderate COVID-19 illness and with major limitations to usual activity 4. Severe COVID-19 or serious disease manifestation from COVID-19 5. Critical illness from COVID-19 or Death Two strata of participants will be identified for analysis purposes. Stratum 2 will be participants who receive direct-acting antivirals (DAAs) or other anti-SARS-CoV2 agents that are approved/available and recommended for use as part of standard of care (SOC), estimated to be about 20% of participants. Stratum 1 will be participants who do not receive this agents, estimated to be about 80% of participants.


Eligibility

Min Age: 18 Years

Inclusion Criteria13

  • Clinical risk based on age ≥ 55 years or an adult (age ≥ 18 years) with an immunosuppressed condition.
  • 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.
  • Within ≤5 days from symptom onset, if symptomatic from current SARS-CoV-2 infection.
  • 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).
  • Participant provides written informed consent prior to study procedures, and understands and agrees to adhere to planned study procedures through Day 28.
  • Ongoing immunosuppressive condition or immunosuppressive treatment, includes:
  • Steroids equivalent to prednisone \> 10 mg/day for at least the last 28 days
  • Rheumatologic or autoimmune disorder treated with a biologic or non-biologic immunosuppressive therapy
  • Antirejection medicine after solid organ or stem cell transplantation
  • Cancer treatment with systemic chemotherapy, biologic and/or cell-based therapy in the last 12 months
  • Primary or acquired severe B- or T-lymphocyte immune dysfunction
  • HIV infection
  • Splenectomy or functional asplenia

Exclusion Criteria11

  • Asymptomatic and had prior symptoms from the current infection that have now resolved (for \>24 hours).
  • Asymptomatic and has received a vaccination for COVID-19 (≥1 dose).
  • Undergoing evaluation for possible admission to hospital for medical management (this does not include evaluation of possible hospitalization for public health purposes).
  • 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).
  • 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).
  • 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.
  • History of hypersensitivity to blood, plasma or IVIG excipients.
  • Known immunoglobulin A (IgA) deficiency or anti-IgA antibodies.
  • 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.

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Interventions

BIOLOGICALHyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)

The hIVIG product is administered as a single dose of 3.5 grams, or 35 milliliter at a concentration of 0.1 grams/milliliter.

OTHERPlacebo

Infusion of 35 milliliters standard isotonic saline


Locations(65)

Southern Arizona VA Healthcare System (074-009)

Tucson, Arizona, United States

VA Northern California Health Care System (074-023)

Mather, California, United States

Stanford University Hospital & Clinics (Site 203-003)

Palo Alto, California, United States

San Francisco VAMC (Site 074-002)

San Francisco, California, United States

Rocky Mountain Regional VA Medical Center (074-010)

Aurora, Colorado, United States

MedStar Health Research Institute

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

Washington DC Veterans Affairs Medical Center

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

University of Maryland Medical System

Baltimore, Maryland, United States

Henry Ford Health System Site (014-001)

Detroit, Michigan, United States

Infusion Associates

Grand Rapids, Michigan, United States

Mount Sinai Beth Israel Hospital

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Cleveland Clinic Foundation (Site 207-001)

Cleveland, Ohio, United States

Penn State Health Milton S. Hershey Medical Center (209-002)

Hershey, Pennsylvania, United States

Hendrick Medical Center

Abilene, Texas, United States

CHRISTUS Spohn Shoreline Hospital

Corpus Christi, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Intermountain Medical Center (211-001)

Murray, Utah, United States

UVA Health System, University Hospital (Site 210-003)

Charlottesville, Virginia, United States

Carilion Medical Center (Site 080-018)

Roanoke, Virginia, United States

Salem VA Medical Center (074-014)

Salem, Virginia, United States

Swedish Hospital First Hill

Seattle, Washington, United States

Instituto Medico Platense

La Plata, Buenos Aires, Argentina

Centro de Investigaciones Medicas de Mar del Plata (Site 611-031)

Mar del Plata, Buenos Aires, Argentina

Clínica Central S.A. (611-028)

Villa Regina, Río Negro Province, Argentina

Hospital General de Agudos JM Ramos Mejia

Buenos Aires, Argentina

St. Vincent's Hospital

Sydney, New South Wales, Australia

Odense University Hospital

Odense, C, Denmark

Aarhus Universitetshospital, Skejby

Aarhus, N, Denmark

Department of Infectious Diseases

Aalborg, Denmark

Rigshospitalet, CHIP

Copenhagen, Denmark

Bispebjerg Hospital

Copenhagen, Denmark

Herlev/Gentofte Hospital

Hellerup, Denmark

Hvidovre University Hospital, Department of Infectious Diseases

Hvidovre, Denmark

Kolding Sygehus

Kolding, Denmark

Dept of Critical Care and Pulmonary Medicine, Evangelismos General Hospital

Athens, Attica, Greece

3rd Dept of Medicine, Medical School

Athens, Attica, Greece

Laiko Athens General Hospital

Athens, Attica, Greece

Department of Clinical Therapeutics of Alexandra Hospital

Athens, Attica, Greece

4th Department of Internal Medicine

Athens, Attica, Greece

All India Institute of Medical Sciences (AIIMS)

Jodhpur, Rajasthan, India

Postgraduate Institute of Medical Education and Research (PGIMER)

Chandigarh, India

Hospital General Dr. Manuel Gea Gonzáles

Mexico City, Mexico City, Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico City, Mexico

Instituto Nacional de Enfermedades Respiratorias Ismael Cosió Villegas

Mexico City, Mexico City, Mexico

CHRISTUS Centro de Excelencia en Investigacion (Obispado)

Monterrey, Nuevo León, Mexico

Hospital General Dr. Aurelio Valdivieso

Oaxaca City, OA, Mexico

Unidad de Ensayos Clinicos Socios En Salud Sucursal Perú (651-009)

Lima, Peru

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

CAP Can Bou

Castelldefels, Barcelona, Spain

CAP El Maresme

Mataró, Barcelona, Spain

CAP Corbera

Barcelona, Spain

Siriraj Hospital (Site 613-002)

Bangkok Noi, Bangkok, Thailand

Chulalongkorn University and The HIV-NAT

Pathum Wan, Bangkok, Thailand

Khon Kaen University, Srinagarind Hospital (Site 613-003)

Khon Kaen, Thailand

Bamrasnaradura Infections Diseases Institute (613-007)

Nonthaburi, Thailand

MRC/UVRI & LSHTM Uganda Research Unit

Entebbe, Uganda

Joint Clinical Research Center (JCRC)

Kampala, Uganda

Makerere University Lung Institute (Site 634-604)

Kampala, Uganda

St. Francis Hospital, Nsambya

Kampala, Uganda

Lira Regional Referral Hospital

Lira, Uganda

Masaka Regional Referral Hospital

Masaka, Uganda

Central City Clinical Hospital of Ivano-Frankivsk City Council

Ivano-Frankivsk, Ukraine

University College London Hospitals

London, United Kingdom

Royal Victoria Infirmary

Newcastle upon Tyne, United Kingdom

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