trimodulin (BT588) / Grifols - LARVOL DELTA

Early Health Outcomes Model on the Impact of Trimodulin in the Management of Patients With Severe Community-Acquired Pneumonia on Invasive Mechanical Ventilation Based on the CIGMA Phase 2 Randomized Placebo-Controlled Trial (ISPOR 2025) - "Adding trimodulin to SoC reduces ICU LOS and mortality, leading to improved LE and QALYs in patients with sCAP on IMV compared to SoC alone. The effects are more pronounced in patients with inflammatory disease stage, indicated by CRP levels ≥70mg/L."

Clinical • HEOR • P2 data • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • CRP

ESsCAPE: Efficacy and Safety of Trimodulin (BT588) in Subjects with Severe Community-acquired Pneumonia (sCAP) (clinicaltrials.gov) - P3 | N=590 | Recruiting | Sponsor: Biotest | Trial completion date: Apr 2025 ➔ Dec 2026 | Trial primary completion date: Feb 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Infectious Disease • Pneumonia • Respiratory Diseases • CRP

TRICOVID: Efficacy and Safety of Trimodulin (BT588) in Subjects With CAP Including COVID-19 Pneumonia (clinicaltrials.gov) - P3 | N=390 | Active, not recruiting | Sponsor: Biotest | Trial completion date: Aug 2025 ➔ May 2025 | Recruiting ➔ Active, not recruiting | Trial primary completion date: Aug 2025 ➔ May 2025

Enrollment closed • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL6

Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID). (PubMed, Eur J Med Res) - P2 | "Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESSCOVID WAS REGISTERED PROSPECTIVELY AT CLINICALTRIALS.GOV ON OCTOBER 6, 2020.: NCT04576728."

Journal • P2 data • Critical care • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Thrombocytopenia

MODULATION OF NET RELEASE BY PLASMA DERIVED IMMUNOGLOBULINS: TRIMODULIN (POLYVALENT IGM, IGA, IGG SOLUTION) VS. STANDARD IVIG (EWRR 2024) - No abstract available

Inflammation

Modulation of NET release by plasma derived immunoglobulins: Trimodulin (polyvalent IgM, IgA, IgG solution) vs. standard IVIg (ISICEM 2024) - "The results of this in vitro study demonstrate that modulation of NET release may be a viable mode of action for trimodulin, which may be relevant in the treatment of severe lung infectious diseases. The superior immunomodulatory effects of trimodulin on neutrophils could be mediated by the additional IgM and IgA antibodies within trimodulin. Further studies are needed to unravel the mechanism and clinical relevance of these findings."

Infectious Disease • Respiratory Diseases

ESsCAPE: Efficacy and Safety of Trimodulin (BT588) in Subjects With Severe Community-acquired Pneumonia (sCAP) (clinicaltrials.gov) - P3 | N=590 | Recruiting | Sponsor: Biotest | Trial completion date: Dec 2024 ➔ Apr 2025

Trial completion date • Infectious Disease • Pneumonia • Respiratory Diseases • CRP

TRICOVID: Efficacy and Safety of Trimodulin (BT588) in Subjects With CAP Including COVID-19 Pneumonia (clinicaltrials.gov) - P3 | N=390 | Recruiting | Sponsor: Biotest | Trial completion date: Mar 2024 ➔ Aug 2025 | Trial primary completion date: Mar 2024 ➔ Aug 2025

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL6

The immunomodulating activity of trimodulin (polyvalent IgM, IgA, IgG solution): a post hoc analysis of the phase II CIGMA trial. (PubMed, Crit Care) - "This post hoc pharmacodynamic analysis of a blinded phase II trial suggests that trimodulin compensates for, and more rapidly modifies, the dysregulated inflammatory response seen in sCAP patients. Trimodulin was associated with significantly lower mortality and more VFD in subgroups with high CRP and low ALC. This effect was particularly marked in patients who also had low baseline IgM values. These findings require confirmation in prospective trials."

Immunomodulating • Journal • P2 data • Retrospective data • Immunology • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • CRP

Biochemical Characterization of a New 10% IVIG Preparation [IgG Next Generation (BT595)/Yimmugo] Obtained from a Manufacturing Process Preserving IgA/IgM Potential of Human Plasma. (PubMed, Drugs R D) - "Yimmugo constitutes a new high quality IVIG preparation derived from a novel manufacturing process that takes advantage of the full therapeutic immunoglobulin potential of human plasma."

Journal • Infectious Disease

ESsCAPE: Efficacy and Safety of Trimodulin (BT588) in Subjects With Severe Community-acquired Pneumonia (sCAP) (clinicaltrials.gov) - P3 | N=590 | Recruiting | Sponsor: Biotest | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2023 ➔ Jun 2023

Enrollment open • Trial initiation date • Infectious Disease • Pneumonia • Respiratory Diseases • CRP

ESsCAPE: Efficacy and Safety of Trimodulin (BT588) in Subjects With Severe Community-acquired Pneumonia (sCAP) (clinicaltrials.gov) - P3 | N=590 | Not yet recruiting | Sponsor: Biotest

New P3 trial • Infectious Disease • Pneumonia • Respiratory Diseases • CRP

ESsCOVID: Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19 (clinicaltrials.gov) - P2 | N=166 | Completed | Sponsor: Biotest | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • CRP

TRICOVID: Efficacy and Safety of Trimodulin (BT588) in Subjects With Moderate or Severe COVID-19 (clinicaltrials.gov) - P3 | N=334 | Recruiting | Sponsor: Biotest | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2022 ➔ Jan 2023

Enrollment open • Trial initiation date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

TRICOVID: Efficacy and Safety of Trimodulin (BT588) in Subjects With Moderate or Severe COVID-19 (clinicaltrials.gov) - P3 | N=334 | Not yet recruiting | Sponsor: Biotest

New P3 trial • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

A randomized, placebo-controlled, double-blind, multi-center, phase III trial to assess the efficacy and safety of trimodulin (BT588) in adult hospitalized subjects with moderate or severe COVID-19 (clinicaltrialsregister.eu) - P3 | N=334 | Ongoing | Sponsor: Biotest AG

New P3 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP

Is trimodulin better? (ISICEM 2022) - No abstract available

The Functional Role of IgA in the IgM/IgA-Enriched Immunoglobulin Preparation Trimodulin. (PubMed, Biomedicines) - "The fine-tuned balance between immunomodulatory and anti-pathogenic effects of trimodulin were shown to be dose-dependent. Summarized, our data demonstrate the functional role of IgA in trimodulin, highlighting the importance of this immunoglobulin class in immunoglobulin therapy."

Journal • Immune Modulation • Immunology • Inflammation

Polyvalent immunoglobulin preparations inhibit pneumolysin-induced platelet destruction. (PubMed, Thromb Haemost) - "In this study, we compared the efficacy of a standard intravenous immunoglobulin preparation (IVIG, 98% IgG; Privigen, CSL Behring, USA) and an IgM/IgA-enriched immunoglobulin preparation (21% IgA, 23% IgM, 56% IgG; trimodulin, Biotest AG, Germany) to inhibit pneumolysin-induced platelet destruction. The capacity to antagonize pneumolysin mainly depended on the final IgG content. As both polyvalent immunoglobulin preparations efficiently prevent pneumolysin-induced platelet destruction and maintain platelet function in vitro, they represent promising candidates for clinical studies on supportive treatment of pneumococcal pneumonia to reduce progression of respiratory distress."

Journal • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases

The Dual Role of a Polyvalent IgM/IgA-Enriched Immunoglobulin Preparation in Activating and Inhibiting the Complement System. (PubMed, Biomedicines) - "IgM/IgA provide a balancing effect on the complement system. Trimodulin may enhance phagocytosis and opsonophagocytosis in patients with severe infections and prevent excessive pathogen lysis and release of harmful anaphylatoxins."

Journal • Immune Modulation • Immunology • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases

Immunomodulation: Immunoglobulin Preparations Suppress Hyperinflammation in a COVID-19 Model via FcγRIIA and FcαRI. (PubMed, Front Immunol) - "We show that COVID-19 associated inflammation could be reduced by addition of human immunoglobulin preparations (IVIG and trimodulin), while trimodulin elicits stronger immune modulation by more powerful ITAMi signaling. Besides IgG, the IgA component of trimodulin in particular, is of functional relevance for immune modulation in this assay setup, highlighting the need to study IgA mediated immune response."

Journal • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

ESsCOVID: Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19 (clinicaltrials.gov) - P2; N=164; Active, not recruiting; Sponsor: Biotest; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • CRP

ESsCOVID: Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19 (clinicaltrials.gov) - P2; N=164; Recruiting; Sponsor: Biotest; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease

ESsCOVID: Efficacy and Safety of Trimodulin in Subjects With Severe COVID-19 (clinicaltrials.gov) - P2; N=164; Not yet recruiting; Sponsor: Biotest

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease

Biotest AG: Biotest phase II study for the treatment of severe COVID-19 patients with trimodulin approved (PharmiWeb) - "Biotest announced today that the ESsCOVID (Escape from severe COVID-19) trial for treatment of COVID-19 patients with trimodulin was approved by...Ethics Committee in Spain. In addition, the study has now also been submitted for approval in Russia and Brazil....Approximately 160 adult patients with severe COVID-19 are planned to be enrolled....Biotest aims for an expedited approval of trimodulin....'With the approval of the trial we are now preparing the initiation of selected study centers...'"

New P2 trial • Infectious Disease • Novel Coronavirus Disease