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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04910269




Registration number
NCT04910269
Ethics application status
Date submitted
1/06/2021
Date registered
2/06/2021
Date last updated
8/10/2024

Titles & IDs
Public title
Outpatient Treatment With Anti-Coronavirus Immunoglobulin
Scientific title
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
Secondary ID [1] 0 0
2021-001663-24
Secondary ID [2] 0 0
INSIGHT12
Universal Trial Number (UTN)
Trial acronym
OTAC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID 0 0
SARS-CoV2 Infection 0 0
Covid19 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)
Other interventions - Placebo

Experimental: Treatment Group - Participants in this group will receive the investigational treatment in addition to standard of care.

Placebo comparator: Placebo Group - Participants in this group will receive a placebo in addition to standard of care.


Treatment: Other: Hyperimmune 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.

Other interventions: Placebo
Infusion of 35 milliliters standard isotonic saline
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinical Status
Timepoint [1] 0 0
7 days
Secondary outcome [1] 0 0
All-cause hospitalization or death through 28 days.
Timepoint [1] 0 0
28 days
Secondary outcome [2] 0 0
All-cause mortality through 28 days.
Timepoint [2] 0 0
28 days
Secondary outcome [3] 0 0
Significant Disease Progression
Timepoint [3] 0 0
28 days
Secondary outcome [4] 0 0
Ordinal Scale Distribution
Timepoint [4] 0 0
4, 14, 28 days
Secondary outcome [5] 0 0
Disease Progression Through 7 Days
Timepoint [5] 0 0
7 days
Secondary outcome [6] 0 0
Significant Disease Progression Through 7 Days
Timepoint [6] 0 0
7 days
Secondary outcome [7] 0 0
Disease Progression at Follow-up
Timepoint [7] 0 0
7, 14, 28 days
Secondary outcome [8] 0 0
Activity Limitations at Follow-up
Timepoint [8] 0 0
7, 14, 28 days
Secondary outcome [9] 0 0
Change in Viral Burden from Serum Antigen
Timepoint [9] 0 0
7 days
Secondary outcome [10] 0 0
Change in Viral Burden from PCR
Timepoint [10] 0 0
7 days
Secondary outcome [11] 0 0
Change in SARS-CoV-2 Antibody Concentration
Timepoint [11] 0 0
7 days
Secondary outcome [12] 0 0
Healthcare Utilization at Follow-up
Timepoint [12] 0 0
28 days
Secondary outcome [13] 0 0
Worst Status Through 28 Days
Timepoint [13] 0 0
28 days
Secondary outcome [14] 0 0
Hypoxemia Through Day 7
Timepoint [14] 0 0
7 days
Secondary outcome [15] 0 0
Additional COVID-19 Treatment
Timepoint [15] 0 0
28 days

Eligibility
Key inclusion criteria
* 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:

1. Steroids equivalent to prednisone > 10 mg/day for at least the last 28 days
2. Rheumatologic or autoimmune disorder treated with a biologic or non-biologic immunosuppressive therapy
3. Antirejection medicine after solid organ or stem cell transplantation
4. Cancer treatment with systemic chemotherapy, biologic and/or cell-based therapy in the last 12 months
5. Primary or acquired severe B- or T-lymphocyte immune dysfunction
6. HIV infection
7. Splenectomy or functional asplenia
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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:

1. acute coronary syndrome, cerebrovascular syndrome, pulmonary embolism, or deep venous thrombosis within 28 days of randomization.
2. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2026
Actual
Sample size
Target
820
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Denmark
State/province [10] 0 0
C
Country [11] 0 0
Denmark
State/province [11] 0 0
N
Country [12] 0 0
Denmark
State/province [12] 0 0
Aalborg
Country [13] 0 0
Denmark
State/province [13] 0 0
Copenhagen
Country [14] 0 0
Denmark
State/province [14] 0 0
Hellerup
Country [15] 0 0
Denmark
State/province [15] 0 0
Hvidovre
Country [16] 0 0
Denmark
State/province [16] 0 0
Kolding
Country [17] 0 0
Greece
State/province [17] 0 0
Attica
Country [18] 0 0
India
State/province [18] 0 0
Rajasthan
Country [19] 0 0
India
State/province [19] 0 0
Chandigarh
Country [20] 0 0
Mexico
State/province [20] 0 0
Cdmx
Country [21] 0 0
Mexico
State/province [21] 0 0
NL
Country [22] 0 0
Mexico
State/province [22] 0 0
OA
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Thailand
State/province [24] 0 0
Bangkok
Country [25] 0 0
Thailand
State/province [25] 0 0
Khon Kaen
Country [26] 0 0
Thailand
State/province [26] 0 0
Nonthaburi
Country [27] 0 0
Uganda
State/province [27] 0 0
Entebbe
Country [28] 0 0
Uganda
State/province [28] 0 0
Kampala
Country [29] 0 0
Uganda
State/province [29] 0 0
Lira
Country [30] 0 0
Uganda
State/province [30] 0 0
Masaka
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Other
Name
University of Minnesota
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Allergy and Infectious Diseases (NIAID)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Institutes of Health (NIH)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT04910269
Trial related presentations / publications
Jha A, Barker D, Lew J, Manoharan V, van Kessel J, Haupt R, Toth D, Frieman M, Falzarano D, Kodihalli S. Efficacy of COVID-HIGIV in animal models of SARS-CoV-2 infection. Sci Rep. 2022 Oct 10;12(1):16956. doi: 10.1038/s41598-022-21223-2.
Public notes

Contacts
Principal investigator
Name 0 0
Cavan Reilly, PhD
Address 0 0
University of Minnesota
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Gary Collins
Address 0 0
Country 0 0
Phone 0 0
612-626-9006
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04910269