hIVIG for COVID-19

(OTAC Trial)

Recruiting at 54 trial locations

Overseen By Gary Collins

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Minnesota

Disqualifiers: Asymptomatic, Prior COVID-19 vaccination, Pneumonia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1 day

820 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on direct-acting antivirals or other anti-SARS-CoV2 agents, you may be included in a specific group for analysis.

What data supports the effectiveness of the drug hIVIG for COVID-19?

Research in animal models, such as mice and hamsters, shows that a similar drug, COVID-HIGIV, significantly reduced the virus in the lungs and improved recovery from infection. This suggests that hIVIG might also be effective in treating COVID-19. ^{1 2 3 4 5}

Is hIVIG safe for humans?

Animal studies have shown that hIVIG is safe, with no signs of toxicity or allergic reactions. Additionally, in vitro studies (tests done in a lab setting) have shown that hIVIG meets safety standards, suggesting it is safe for further evaluation in humans. ^{1 3 4 6 7}

How is the hIVIG treatment for COVID-19 different from other treatments?

hIVIG is unique because it uses hyperimmune immunoglobulin, which contains a high concentration of antibodies from recovered COVID-19 patients, to provide passive immunity. This treatment is administered intravenously and is designed to offer immediate, specific protection against the virus, unlike vaccines that stimulate the body's own immune response over time. ^{1 2 3 4 8}

Research Team

Cavan Reilly, PhD

Principal Investigator

University of Minnesota

Eligibility Criteria

Adults recently diagnosed with COVID-19, not hospitalized but at high risk due to age (≥55 years), immunosuppression, or certain medical treatments like chemotherapy. Participants must agree not to join other SARS-CoV-2 trials until Day 7 and should have started symptoms within the last 5 days.

Inclusion Criteria

I agree not to join another COVID-19 trial until after Day 7 or until my condition worsens.

I agree not to join another COVID-19 trial until after Day 7 or until my condition significantly worsens.

I am over 55 years old or have a condition that weakens my immune system.

Exclusion Criteria

I have not had a heart attack, stroke, blood clot in my lungs or deep veins in the last 28 days.

You have a known deficiency of immunoglobulin A (IgA) or anti-IgA antibodies.

I have received at least one COVID-19 vaccine dose and feel fine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single infusion of anti-COVID-19 hyperimmune intravenous immunoglobulin (hIVIG) or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at days 7, 14, and 28

4 weeks

3 visits (in-person or virtual)

Long-term Follow-up

Participants are monitored for long-term outcomes such as hospitalization, mortality, and healthcare utilization

28 days

Treatment Details

Interventions

• Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)
• Placebo

Trial Overview The trial is testing if a single infusion of anti-COVID-19 hyperimmune intravenous immunoglobulin (hIVIG) is safer and more effective than a placebo in adults with mild to moderate COVID-19. The study randomly assigns participants to receive either hIVIG or placebo and monitors their health status after seven days.

Participant Groups

Group I: Treatment Group Experimental Treatment 1 Intervention

Participants in this group will receive the investigational treatment in addition to standard of care.

Group II: Placebo Group Placebo Group 1 Intervention

Participants in this group will receive a placebo in addition to standard of care.

Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) is already approved in United States, European Union for the following indications:

Approved in United States as hIVIG for:

• Severe COVID-19 in hospitalized patients
• Prevention of severe COVID-19 in immunocompromised patients

Approved in European Union as hIVIG for:

• Severe COVID-19 in hospitalized patients
• Prevention of severe COVID-19 in immunocompromised patients

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)

Collaborator

Trials

15

Recruited

8,800+

Findings from Research

In a study involving 593 hospitalized COVID-19 patients, hyperimmune intravenous immunoglobulin (hIVIG) did not show significant efficacy in improving outcomes compared to placebo when administered alongside standard care, including remdesivir.

While hIVIG infusions were generally well tolerated, they were associated with a higher rate of infusion reactions (18.6% vs 9.5% for placebo), and safety outcomes varied based on the presence of neutralizing antibodies, indicating potential risks for certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial. [2023]

COVID-HIGIV, a human immunoglobulin product, significantly improved survival rates in SARS-CoV-2 infected transgenic mice, indicating its potential as an effective treatment for COVID-19.

The pharmacokinetic profiles of COVID-HIGIV were similar in both healthy and infected mice, suggesting that it can be administered safely and effectively shortly after exposure to the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Effects of Polyclonal Antibodies against SARS-CoV2 in Mice. Jha, A., Doyle-Eisele, M., Revelli, D., et al.[2023]

In a randomized trial involving 461 asymptomatic adults with confirmed SARS-CoV-2 infection, subcutaneous administration of anti-COVID-19 hyperimmune immunoglobulin (C19-IG20%) did not significantly prevent the development of symptomatic COVID-19 compared to placebo.

The treatment was found to be safe, with similar rates of adverse events across all groups, and no severe or life-threatening reactions were reported, indicating that while the treatment was safe, it lacked efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial. Alemany, A., Millat-Martinez, P., Corbacho-Monné, M., et al.[2023]

Hyperimmune immunoglobulin (hIVIG) prepared from humans shows little to no impact on all-cause mortality and clinical improvement in hospitalized patients with moderate-to-severe COVID-19, based on a review of five randomized controlled trials involving 947 participants.

Equine-derived polyclonal antibodies (EpAbs) may reduce mortality and serious adverse events in COVID-19 patients, suggesting potential benefits over hIVIG, although the evidence is still low-certainty and further studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperimmune immunoglobulin for people with COVID-19. Kimber, C., Valk, SJ., Chai, KL., et al.[2023]

COVID-HIGIV, an anti-SARS-CoV-2 immunoglobulin, significantly reduced viral load in the lungs of both hamster and mouse models, indicating its potential effectiveness against COVID-19.

Treatment with COVID-HIGIV also led to less body weight loss and faster recovery to baseline weight in infected animals, along with reduced lung inflammation and damage, supporting its further evaluation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of COVID-HIGIV in animal models of SARS-CoV-2 infection. Jha, A., Barker, D., Lew, J., et al.[2023]

The development of intravenous anti-COVID-19 hyperimmune immunoglobulin resulted in a product with a high concentration of neutralizing antibodies (9.4 times concentrated) and a protein content of 98.1 mg/ml, primarily consisting of IgG (97.6%).

Safety studies in animal models showed no toxicity or allergic reactions, and the immunoglobulin effectively protected immunosuppressed hamsters from SARS-CoV-2, paving the way for future clinical trials in healthy adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and characterization of anti-SARS-CoV-2 intravenous immunoglobulin from COVID-19 convalescent plasma. Razumikhin, M., Smolyanova, T., Nikolaeva, A., et al.[2022]

A new formulation of anti-SARS-CoV-2 intravenous immunoglobulins (VP-IVIg) derived from plasma of vaccinated donors showed higher concentrations of neutralizing antibodies compared to a similar formulation from convalescent donors (CP-IVIg), indicating potentially greater efficacy against COVID-19.

Both VP-IVIg and CP-IVIg met safety and quality standards for intravenous immunoglobulin formulations, suggesting that VP-IVIg could be a viable therapeutic option for immunocompromised patients or those with severe COVID-19, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro Characterization of Anti-SARS-CoV-2 Intravenous Immunoglobulins (IVIg) Produced From Plasma of Donors Immunized With the BNT162b2 Vaccine and Its Comparison With a Similar Formulation Produced From Plasma of COVID-19 Convalescent Donors. Rojas-Jiménez, G., Solano, D., Segura, Á., et al.[2022]

In a randomized controlled trial involving severely immunocompromised hospitalized COVID-19 patients, treatment with COVIG (hyperimmune globulin) significantly reduced the incidence of severe COVID-19, with only 20% of patients experiencing severe disease compared to 88% in the IVIG control group.

These results suggest that COVIG may be an effective treatment option for patients who are severely immunocompromised and hospitalized with COVID-19, especially when other therapies like monoclonal antibodies are not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019: A Randomized, Controlled Trial. Huygens, S., Hofsink, Q., Nijhof, IS., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Effects of Polyclonal Antibodies against SARS-CoV2 in Mice. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Hyperimmune immunoglobulin for people with COVID-19. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy of COVID-HIGIV in animal models of SARS-CoV-2 infection. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Development and characterization of anti-SARS-CoV-2 intravenous immunoglobulin from COVID-19 convalescent plasma. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

In vitro Characterization of Anti-SARS-CoV-2 Intravenous Immunoglobulins (IVIg) Produced From Plasma of Donors Immunized With the BNT162b2 Vaccine and Its Comparison With a Similar Formulation Produced From Plasma of COVID-19 Convalescent Donors. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019: A Randomized, Controlled Trial. [2023]