hIVIG for COVID-19

(OTAC Trial)

Recruiting at 54 trial locations

Overseen By Mamta Jain, MD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called hyperimmune intravenous immunoglobulin (hIVIG) to determine its effectiveness for people recently diagnosed with COVID-19 who do not require hospitalization. The researchers aim to discover if a single infusion of hIVIG can improve symptoms and overall health compared to a placebo. Suitable candidates for this trial include adults who tested positive for COVID-19 within the last 5 days and have an ongoing condition that weakens their immune system, such as taking certain medications or having HIV. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that a treatment called hyperimmune intravenous immunoglobulin (hIVIG) is being tested for safety in treating COVID-19. One study found that by the seventh day after treatment, the safety of hIVIG was similar to a placebo, with both groups experiencing similar side effects. Another article mentions ongoing uncertainty about the effectiveness and safety of hIVIG for COVID-19 patients. However, results so far have not revealed any major safety concerns.

Since this trial is in an advanced phase, earlier tests likely indicated that the treatment is generally well-tolerated. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COVID-19?

Most treatments for COVID-19 focus on antiviral drugs or anti-inflammatory medications to reduce symptoms and viral load. However, hIVIG (hyperimmune immunoglobulin) is unique because it harnesses antibodies specifically targeting SARS-CoV-2, the virus causing COVID-19. This treatment is derived from the plasma of recovered COVID-19 patients, providing a concentrated dose of antibodies that can bolster the immune response more directly than standard options. Researchers are excited about hIVIG because it has the potential to offer immediate immune support, potentially reducing the severity and duration of COVID-19 symptoms more effectively than existing treatments.

What evidence suggests that hIVIG might be an effective treatment for COVID-19?

Research has shown that hyperimmune immunoglobulin (hIVIG), a treatment available to participants in this trial, may aid in managing COVID-19. One study found that hIVIG improved survival chances for COVID-19 patients with weakened immune systems. Another study suggested that hIVIG could lessen the severity of COVID-19 symptoms. These findings indicate that hIVIG might help people recover better if they are recently diagnosed with COVID-19. Although more research is needed, early results are promising for those considering this treatment. ^{1 3 6 7 8}

Who Is on the Research Team?

Cavan Reilly, PhD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

Citations

1. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(22)00101-5/fulltext

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

2. sciencedirect.com sciencedirect.com/science/article/pii/S2589537023000755

Articles Subcutaneous anti-COVID-19 hyperimmune ... We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9887673/

Hyperimmune immunoglobulin for people with COVID‐19 - PMC Several clinical trials investigating the safety and effectiveness of hIVIG were conducted, and their results must be interpreted with care. Thus, we must ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04910269

Study Details | NCT04910269 | Outpatient Treatment With ... 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 ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2808084

SARS-CoV-2 Hyperimmune Immunoglobulins Following ... Recently, survival benefit was observed for patients with COVID-19 and immunodeficiency treated with hyperimmune anti-SARS-CoV-2 IVIGs (hCoV-2IG) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35093205/

a double-blind, placebo-controlled, phase 3, randomised trial Hyperimmune immunoglobulin for hospitalised patients with COVID-19 ... safety outcome at day 7 was similar for the hIVIG (24%) and placebo ...

7. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015167.pub2/full

Hyperimmune immunoglobulin for people with COVID‐19 We are uncertain whether hyperimmune immunoglobulin is an effective treatment for people hospitalised with COVID‐19, and whether it affects the number of ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8506918/

Hyperimmune immunoglobulin for people with COVID‐19 - PMC Using a living systematic review approach, to assess whether hyperimmune immunoglobulin therapy is effective and safe in the treatment of people with COVID-19.