Pentaglobin (human immune globulin IV 10%) / Grifols - LARVOL DELTA

Management of Multi-Drug-Resistant Acinetobacter baumannii Infection in Heart Transplant Patients (ISHLT 2025) - "6 patients with septic shock were treated with iv Pentaglobin 0,25 g/Kg at 12 mL/h for 3 days, a solution containing human plasma proteins, 95 % immunoglobulins (IgG, IgM and IgA). 5 patients developed septic pancytopenia, severe drop of leuocytes, we administered Filgrastim 48 MU for 3 days, an originator recombinant human granulocyte colony-stimulating factor...All other patients are reported fine, leading an autonomous life at home.Conclusion Management of MDR pathogens such as AB is particularly challenging in heart transplants because of concomitant factors of fragility, such as recovering hemodynamics of the early stages and intense immunosuppression. Combining antibiogram-guided therapy, blood purification methods, modulation of immunosuppressants was successful in managing these clinical scenarios."

Clinical • Cerebral Hemorrhage • Hematological Disorders • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • Septic Shock • Transplantation

PENTAGLOBIN® AS EARLY ADJUVANT TREATMENT FOR FEBRILE NEUTROPENIA IN HEMATOLOGICAL PATIENTS COLONIZED BY CARBAPENEM-RESISTANT ENTEROBACTERIACEAE OR PSEUDOMONAS AERUGINOSA: PRELIMINARY ANALYSIS OF GITMO STUDY "PENTALLO" (EBMT 2025) - P2 | "Our preliminary data confirm the relevance of colonization or previous infection by CRE and PA in predicting infection by the same pathogen during neutropenia. Pentaglobin® in association to targeted antimicrobial therapy was able to reduce infection-related mortality in neutropenic hematological patients with a colonization or previous infection by CRE or PA. Clinical Trial Registry: EudraCT 2018-001344-57"

Clinical • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia

PENTALLO: Pentaglobin in CRE and PA Neutropenic Infections (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Gruppo Italiano Trapianto di Midollo Osseo | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Septic Shock • Transplantation

Role of Immunoglobulin in Male Infertility (clinicaltrials.gov) - P=N/A | N=50 | Recruiting | Sponsor: Dr Salma kafeel Qureshi

New trial • Infertility • Sexual Disorders

PENTAGLOBIN® AS EARLY ADJUVANT TREATMENT FOR FEBRILE NEUTROPENIA IN HEMATOLOGICAL PATIENTS COLONIZED BY CARBAPENEM-RESISTANT ENTEROBACTERIACEAE OR PSEUDOMONAS AERUGINOSA: INTERIM ANALYSIS OF GITMO STUDY “PENTALLO" (EBMT 2024) - P2 | "Preliminary data on 84/120 patients show promising results in term of favorable outcome of neutropenic high risk febrile hematologic patients colonized by CRE or PA treated with Pentaglobin® as adjuvant of the best early antibiotic empiric therapy"

Clinical • Bone Marrow Transplantation • Critical care • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Septic Shock

PENTAGLOBIN® AS EARLY ADJUVANT TREATMENT FOR FEBRILE NEUTROPENIA IN HEMATOLOGICAL PATIENTS COLONIZED BY CARBAPENEM-RESISTANT ENTEROBACTERIACEAE OR PSEUDOMONAS AERUGINOSA: INTERIM ANALYSIS OF GITMO STUDY “PENTALLO" (EBMT 2024) - P2 | "Preliminary data on 84/120 patients show promising results in term of favorable outcome of neutropenic high risk febrile hematologic patients colonized by CRE or PA treated with Pentaglobin® as adjuvant of the best early antibiotic empiric therapy"

Clinical • Bone Marrow Transplantation • Critical care • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Septic Shock

Prospective, Randomized Trial of Personalized Medicine With Pentaglobin® After Surgical Infectious Source Control in Patients With Peritonitis (the PEPPER Trial). (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: RWTH Aachen University | Suspended ➔ Recruiting

Enrollment open • Infectious Disease • Septic Shock • IL6

Sepsis Outcome after Major Abdominal Surgery Does Not Seem to Be Improved by the Use of Pentameric Immunoglobulin IgM: A Single-Center Retrospective Analysis. (PubMed, J Clin Med) - "Based on our results, the use of pentameric IgM does not seem to give any clinical advantages in preventing sepsis after major abdominal surgery."

Journal • Retrospective data • Surgery • Infectious Disease • Septic Shock

Potential role of IgM-enriched immunoglobulin as adjuvant treatment in severe SARS-CoV-2 infection. (PubMed, Minerva Anestesiol) - "The present study offers a significant insight concerning the use of IgM-enriched immunoglobulin preparations in patients with SARS-CoV-2 severe infection and also could identifying the specific immunological and biochemical profile of the patient who can more benefit from this therapeutic option."

Journal • Retrospective data • Critical care • Infectious Disease • Novel Coronavirus Disease • 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

PENTALLO: Pentaglobin in CRE and PA Neutropenic Infections (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Gruppo Italiano Trapianto di Midollo Osseo | Trial completion date: Dec 2023 ➔ Jun 2025 | Trial primary completion date: Apr 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Septic Shock • Transplantation

Septic shock due to c. canimorsus treated with igm-enriched immunoglobulin as adjuvant therapy in an immunocompetent woman (ISICEM 2023) - "Adjuvant therapy with IgM-enriched immunoglobulin (Pentaglobin®) was initiated to restore normal values... Data on immunoglobulin therapy in sepsis is conflicting and there is a lack of evidence in patients with invasive C. canimorsus infection. However, following the administration of immunoglobulins the patient showed sustained clinical improvement. Patients with both a high inflammatory load and IgM deficiency might benefit from therapeutic IgM-administration."

Clinical • Critical care • Infectious Disease • Metabolic Disorders • Respiratory Diseases • Septic Shock • IL6

Efficacy and safety of BT595 (10% human intravenous immunoglobulin) in adult patients with chronic immune thrombocytopenia. (PubMed, Transfus Med) - P3 | "The benefit-risk profile of BT595 is favourable."

Journal • Hematological Disorders • Otorhinolaryngology • Pain • Thrombocytopenia • Thrombocytopenic Purpura

BT595, a 10% Human Normal Immunoglobulin, for Replacement Therapy of Primary Immunodeficiency Disease: Results of a Subcohort Analysis in Children. (PubMed, J Clin Immunol) - P3 | "BT595 is effective, convenient, well tolerated, and safe for the treatment of children with PID."

Journal • Immunology • Infectious Disease • Pediatrics • Primary Immunodeficiency

Efficacy, safety and pharmacokinetics of a new 10% normal human immunoglobulin for intravenous infusion, BT595, in children and adults with primary immunodeficiency disease. (PubMed, Vox Sang) - "BT595 is effective, safe and well tolerated for treating patients with PID."

Journal • PK/PD data • Fatigue • Immunology • Infectious Disease • Pain • Primary Immunodeficiency

PENTALLO: Pentaglobin in CRE and PA Neutropenic Infections (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Gruppo Italiano Trapianto di Midollo Osseo | Trial completion date: Dec 2021 ➔ Dec 2023 | Trial primary completion date: Dec 2021 ➔ Apr 2023

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Septic Shock • Transplantation

A human IgM enriched immunoglobulin preparation, Pentaglobin, reverses autoimmune diabetes without immune suppression in NOD mice. (PubMed, Sci Rep) - "Importantly, the impact of Pentaglobin on the immune system was limited to inhibiting beta cell destruction but was not immune depleting nor did it inhibit the immunization response to an irrelevant antigen. These findings indicate that inhibition of deleterious autoimmunity in T1D is possible while leaving protective immunity fully intact."

Journal • Preclinical • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4 • FOXP3

Personalised Medicine With IgGAM Compared With Standard of Care for Treatment of Peritonitis After Infectious Source Control (the PEPPER Trial) (clinicaltrials.gov) - P2 | N=200 | Suspended | Sponsor: RWTH Aachen University | Trial completion date: Dec 2021 ➔ Jan 2027 | Trial primary completion date: Aug 2021 ➔ Sep 2026

Trial completion date • Trial primary completion date • Infectious Disease • Septic Shock • IL6

IgM/IgA-enriched immunoglobulins – more than an IVIg: about multimeric IgA, IgM & J-chain (ISICEM 2022) - " We characterized the IgM/IgA-enriched immunoglobulin Pentaglobin® (76% IgG, 12% IgA, 12% IgM) by measuring the ratio of IgG and IgA subclasses... The results of this study show the biochemical complexity of polyvalent IgM/IgA-enriched immunoglobulins. The data highlight a substantial portion of multimeric IgM and IgA species. The presence of J-chain indicates the potential secretion of IgA and IgM onto mucosa."

Infectious Disease • Respiratory Diseases

Pentaglobin (immunoglobulin M-enriched immunoglobulin) as adjuvant therapy for premature and very low-birth-weight neonates with sepsis. (PubMed, Indian J Pharmacol) - "Neonatal sepsis is more common in premature and VLBW newborns, and Pentaglobin® management of newborn nosocomial sepsis might be used in addition to other therapies."

Clinical • Journal • Critical care • Infectious Disease • Septic Shock

The use of high-dose immunoglobulin M-enriched human immunoglobulin in dogs with immune-mediated hemolytic anemia. (PubMed, J Vet Intern Med) - "Treatment with high-dose Pentaglobin was well tolerated by dogs with primary IMHA but no significant advantage was found in this small study. Additional studies examining larger groups and subpopulations of dogs with primary IMHA associated with a poorer prognosis are warranted."

Journal • Anemia • Hematological Disorders • Immunology

Effect of Intravenous IgM-Enriched Immunoglobulins on Presepsin and Other Sepsis Biomarkers. (PubMed, Front Pharmacol) - "It seems possible that Pentaglobin infusion reduces the Presepsin level in a more effective way if it were administered to a younger population (p = 0.012). In conclusion, age modifies the response of Presepsin to Pentaglobin and is a critical variable when investigating the effect of intravenous IgM-enriched immunoglobulins on sepsis."

Biomarker • Journal • Immunology • Infectious Disease • Septic Shock

The Role of IgM-Enriched Immunoglobulin (Pentaglobin) in Septic Patients with Hematological Disease. (PubMed, Int J Hematol Oncol Stem Cell Res) - "Eleven (69%) patients in the control group were alive after 30 days compared to 11 (34%) patients in the intervention group, p= 0.013. There are no apparent benefits in the use of IgM-rich immunoglobulin in septic patients with hematological disease."

Clinical • Journal • Bone Marrow Transplantation • Hematological Disorders • Immunology • Infectious Disease • Septic Shock • Transplantation

"Impact of pentaglobin in severe COVID 19 pneumonia- a prospective study." (PubMed, Int Immunopharmacol) - "The administration of pentaglobin in COVID -19 patients has no significant effect in reducing the risk of mechanical ventilation or death, in disease worsening or in reduction of inflammation."

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

Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia. (PubMed, Sci Rep) - "Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Immune Modulation • Inflammation • Leukemia • Oncology