Trimodulin for Severe Community-acquired Pneumonia

(ESsCAPE Trial)

Recruiting in Palo Alto (17 mi)

+173 other locations

Overseen by Ricard Ferrer Roca, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Biotest

Must not be taking: Immunoglobulins, Interferons, Immunosuppressants

Disqualifiers: Pregnancy, ECMO, Severe lung disease, others

Stay on Your Current Meds

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests if trimodulin, added to usual care, helps adults with severe lung infections who need breathing machines recover faster by boosting their immune system.

Do I need to stop my current medications to join the trial?

The trial requires that you stop certain medications before starting the treatment. Specifically, you must not have been treated with polyvalent immunoglobulin preparations in the last 21 days, certain predefined medications in the last 2 days, or any type of interferon in the last 21 days before starting the trial treatment.

What data supports the effectiveness of the drug Trimodulin for severe community-acquired pneumonia?

Research shows that Trimodulin, a mix of different antibodies, helped reduce death rates in patients with severe pneumonia who had high levels of inflammation markers. It also helps balance the immune system, which can be beneficial in fighting severe infections. ^{1 2 3 4 5}

Is trimodulin safe for humans?

Trimodulin has been studied in patients with severe community-acquired pneumonia and showed a good safety profile, with no major safety concerns reported. It has also been tested for its immune-modulating effects in other conditions, like COVID-19, and was found to help reduce inflammation without significant safety issues. ^{1 2 3 4 5}

Research Team

Ricard Ferrer Roca, MD

Principal Investigator

Hospital Vall d'Hebron

Eligibility Criteria

Adults hospitalized with severe community-acquired pneumonia who need mechanical ventilation can join this trial. They must not have COVID-19, should show signs of inflammation, and agree to use contraception. Excluded are those with severe kidney or liver issues, certain blood disorders, obesity or malnutrition extremes, other serious lung diseases or heart failure, recent cancer treatments outside the lungs/head/neck area, and those on specific medications.

Inclusion Criteria

You have high levels of C-reactive protein, which shows inflammation in your body.

I have been diagnosed with active pneumonia.

Written informed consent

Exclusion Criteria

I am not on immunosuppressants, except for those prescribed for pneumonia.

You have allergies to human proteins or components of trimodulin/placebo.

I haven't had treatments for cancers in the chest, head, neck, or blood in the last year.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive trimodulin or placebo once daily for 5 consecutive days as adjunctive treatment to standard of care

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a follow-up phase comprising maximally 23 days followed by an end-of-follow-up visit/telephone call on day 29 [+3]

23-26 days

End-of-follow-up visit/telephone call on day 29 [+3]

Extended Follow-up

For subjects still in the hospital after day 29, an extended follow-up is conducted until discharge or until day 90. For all subjects alive on day 29, a closing visit/telephone call on day 91 [+10] will be done

Up to 90 days

Closing visit/telephone call on day 91 [+10]

Treatment Details

Interventions

• Placebo (Other)
• Trimodulin (Anti-infective Agent)

Trial Overview The trial is testing Trimodulin as an extra treatment alongside standard care for adults with severe pneumonia requiring breathing support compared to a placebo plus standard care. It also looks at how the body processes Trimodulin and its effects on the disease.

Participant Groups

Group I: Trimodulin Experimental Treatment 1 Intervention

Trimodulin (human IgM, IgA, IgG solution) for intravenous (IV) administration.

Group II: Placebo Placebo Group 1 Intervention

Human albumin 1%

Who Is Running the Clinical Trial?

Biotest

Lead Sponsor

Trials

22

Recruited

2,900+

Findings from Research

In a post hoc analysis of the phase II CIGMA trial involving 160 patients with severe community-acquired pneumonia, trimodulin treatment significantly reduced mortality and increased ventilator-free days, especially in patients with low baseline IgM and low absolute lymphocyte counts.

Trimodulin was shown to rapidly normalize inflammatory markers like procalcitonin and C-reactive protein, indicating its potential to effectively modulate the dysregulated immune response in severe pneumonia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immunomodulating activity of trimodulin (polyvalent IgM, IgA, IgG solution): a post hoc analysis of the phase II CIGMA trial. Singer, M., Torres, A., Heinz, CC., et al.[2023]

In a phase II study involving 160 patients with severe community-acquired pneumonia, trimodulin did not show a significant difference in ventilator-free days or overall mortality compared to placebo.

However, post hoc analyses indicated that trimodulin may reduce all-cause mortality in specific patient subsets with high C-reactive protein and low immunoglobulin M levels, suggesting potential targeted benefits that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study). Welte, T., Dellinger, RP., Ebelt, H., et al.[2021]

Trimodulin, an IgM/IgA-enriched immunoglobulin preparation, activates the complement system and enhances opsonophagocytosis, which helps clear pathogens more effectively compared to standard intravenous IgG preparations.

In patients with severe infections, trimodulin may help balance the complement system, preventing excessive inflammation and tissue damage by inhibiting the complement-dependent cytotoxicity pathway, thus reducing harmful effects associated with severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Dual Role of a Polyvalent IgM/IgA-Enriched Immunoglobulin Preparation in Activating and Inhibiting the Complement System. Schmidt, C., Weißmüller, S., Bohländer, F., et al.[2023]

Trimodulin, a new immunoglobulin preparation containing ~21% IgA, shows significant immunomodulatory and anti-pathogenic effects, particularly through its interaction with the FcαRI receptor on neutrophils.

The IgA component of trimodulin can inhibit inflammation and enhance the phagocytosis of bacteria like Staphylococcus aureus, indicating its important role in immunoglobulin therapy and suggesting that its effects are dose-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Functional Role of IgA in the IgM/IgA-Enriched Immunoglobulin Preparation Trimodulin. Bohländer, F., Weißmüller, S., Riehl, D., et al.[2023]

The study established an in vitro model to investigate how human immunoglobulins, particularly IgA and IgG, modulate inflammation in COVID-19, revealing that both types of antibodies play important roles in immune responses.

Intravenous immunoglobulin preparations, especially trimodulin, were found to effectively reduce COVID-19 related inflammation, with trimodulin showing stronger immune modulation due to its IgA component, suggesting that IgA should be further studied in the context of COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation: Immunoglobulin Preparations Suppress Hyperinflammation in a COVID-19 Model via FcγRIIA and FcαRI. Bohländer, F., Riehl, D., Weißmüller, S., et al.[2022]

References

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

The immunomodulating activity of trimodulin (polyvalent IgM, IgA, IgG solution): a post hoc analysis of the phase II CIGMA trial. [2023]

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

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study). [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Dual Role of a Polyvalent IgM/IgA-Enriched Immunoglobulin Preparation in Activating and Inhibiting the Complement System. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Functional Role of IgA in the IgM/IgA-Enriched Immunoglobulin Preparation Trimodulin. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Immunomodulation: Immunoglobulin Preparations Suppress Hyperinflammation in a COVID-19 Model via FcγRIIA and FcαRI. [2022]