Trimodulin for Severe Community-acquired Pneumonia

(ESsCAPE Trial)

Recruiting at 156 trial locations

Overseen By Claudia Schulte

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Biotest

Must not be taking: Immunoglobulins, Interferons, Immunosuppressants

Disqualifiers: Pregnancy, ECMO, Severe lung disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: 120

Duration: 5 days

590 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called trimodulin for individuals with severe community-acquired pneumonia, a serious lung infection requiring mechanical ventilation. Researchers aim to determine if trimodulin, when added to standard care, is safer and more effective than a placebo plus standard care. The trial seeks patients hospitalized with pneumonia who need mechanical ventilation. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that trimodulin, a new antibody treatment, has undergone testing to ensure safety. In earlier studies, patients with severe community-acquired pneumonia (a serious lung infection) who received trimodulin experienced better health outcomes. Most importantly, trimodulin was generally well-tolerated, with most people not experiencing serious side effects.

Previous trials examined the use of trimodulin alongside standard care to determine its effectiveness in aiding recovery. The results suggested that trimodulin is safe for patients with severe pneumonia. While some side effects occurred, they were mostly mild and infrequent.

Overall, testing has suggested that trimodulin is safe for people with severe pneumonia. The current trial is in a later stage, indicating that trimodulin has already demonstrated likely safety in earlier tests. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Trimodulin is unique because it combines three types of antibodies—IgM, IgA, and IgG—into one intravenous solution. Unlike standard treatments for severe community-acquired pneumonia, which typically involve antibiotics and supportive care, Trimodulin specifically targets multiple pathways of the immune system. This multi-pronged approach could enhance the body's ability to fight off infections more effectively, offering a potentially powerful alternative to current therapies. Researchers are excited about Trimodulin because it might provide quicker and more robust responses in patients who are severely ill.

What evidence suggests that trimodulin might be an effective treatment for severe community-acquired pneumonia?

Research has shown that trimodulin, which participants in this trial may receive, may help treat severe community-acquired pneumonia (sCAP). In earlier studies, trimodulin boosted the body's ability to fight bacteria. This treatment combines antibodies that work together to combat infections more effectively. Early results indicated that patients who received trimodulin had better outcomes than those who only received standard treatment. These findings suggest that trimodulin is a promising option for people with severe pneumonia who need extra support. ^{1 2 3 4 6}

Who Is on the Research Team?

Ricard Ferrer Roca, MD

Principal Investigator

Hospital Vall d'Hebron

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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]

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Trimodulin

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05722938

Efficacy and Safety of Trimodulin (BT588) in Subjects With ... The main objective of the trial is to assess the efficacy and safety of trimodulin as adjunctive treatment to standard of care (SoC) compared to placebo ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5924663/

Efficacy and safety of trimodulin, a novel polyclonal ... A novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, ...

3. biotest.com biotest.com/de/en/r_d/pipeline/trimodulin.cfm

Trimodulin Biotest's IgM Concentrate shows encouraging results in life-threatening pneumonia - Phase II trial with IgM Concentrate completed in patients with severe ...

4. publications.ersnet.org publications.ersnet.org/content/erj/early/2025/08/07/1399300300392-2025

Trimodulin Supports Antibacterial Defence and Restricts ... Our findings in preclinical pneumonia models suggest that trimodulin could be a promising therapy for sCAP patients. We provide evidence that ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05531149

Efficacy and Safety of Trimodulin (BT588) in Subjects With ... The main objectives of the trial are to assess the efficacy and safety of trimodulin as adjunctive treatment to standard of care (SoC) compared to placebo ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11321023/

Efficacy and safety of trimodulin in patients with severe COVID ... In a previous phase II clinical trial, trimodulin improved outcomes of patients with severe community-acquired pneumonia (sCAP) on invasive ...