Flebogamma 5% DIF (human immune globulin intravenous 5%) / Grifols - LARVOL DELTA

Incidence of BK Virus Replication in Patients Undergoing HLA and ABO Desensitization (WTC 2025) - "The desensitization protocol was similar for both: Rituximab 375 mg/m² one month before transplantation, except in HLA DD, where it was administered at the end of apheresis and immunoglobulin sessions... The incidence of BK virus replication in high immunological risk patients is higher in ABOi compared to HLAi (LD). It is lower than in HLAi (DD) patients, although the latter group universally receives thymoglobulin. In desensitization protocols with living donors, a significant difference was observed in patients who received CMV-specific immunoglobulin, although its role remains to be defined."

Clinical • Infectious Disease • Renal Disease

Attenuation of neutrophil adhesion and formation of neutrophil extracellular traps by pooled human immune globulins. (PubMed, Front Pharmacol) - "These findings show the dose-dependent efficacy of pooled human immune globulins, specifically Flebogamma® DIF against experimentally and pathologically induced NETosis and neutrophil adhesion to corneal epithelial cells, in vitro. The results from this study support the continued clinical development of Flebogamma® 5% DIF as a novel and efficacious treatment for the signs and symptoms of dry eye disease."

Journal • Dry Eye Disease • Ophthalmology

Safety and tolerability of pooled human immune globulins after topical ophthalmic administration in New Zealand White rabbits. (PubMed, Cutan Ocul Toxicol) - "Administration of immune globulins had no effect on intraocular pressure. Flebogamma® 5% DIF and Flebogamma® 10% DIF were well-tolerated by NZW rabbits following single and repeat dose topical ophthalmic administration, supporting the future development of topical pooled human immune globulins for the treatment of ocular surface disease."

Journal • Preclinical • Dry Eye Disease • Ophthalmology

Rapid desensitization to intravenous immunoglobulins (EAACI 2023) - "The desensitization procedure consisted of a 3-solution 12-step protocol with Plangamma®, Flebogamma® or Privigen®, administered at fixed intervals every 15 minutes until the target dose was reached.ResultsThe initial adverse reactions reported were cutaneous symptoms (urticaria and erythema) in all patients, and hypotension in 1 patient...Undiluted IDTs yielded a positive result with Plangamma® (50mg/ml) in 1, and Flebogamma® (50mg/ml) in 1 out of 4 patients...All desensitizations were tolerated and a total of 48 rapid desensitizations were successfully administered. ConclusionA rapid desensitization procedure to IVIG has shown to be safe and effective in patients with a hypersensitivity reaction to immunoglobulins."

Allergy • Immunology

Surveillance of anti-SARS-CoV-2 antibodies in plasma pools and in immunoglobulin medicinal products manufactured since 2020 has shown high neutralizing activity against SARS-CoV-2 and current variants (CIS 2023) - "Methods Healthy donors plasma pools collected in the US and Europe, and the subsequent intravenous (Flebogamma DIFand Gamunex-C, Grifols) and subcutaneous (Xembify, Grifols) IgG manufactured batches were followed from March 2020...Intravenous and subcutaneous IgG products efficiently neutralized the current circulating VOC, Omicron BA.5. Further research is warranted to assess whether a clinical protective titer against SARS-CoV-2 and passive immunization is achieved in patients with immunodeficiencies treated with IgG products."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

FORCE: Study of the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-polio Syndrome (clinicaltrials.gov) - P2/3 | N=191 | Terminated | Sponsor: Instituto Grifols, S.A. | Active, not recruiting ➔ Terminated

Trial termination

FORCE: Study of the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-polio Syndrome (clinicaltrials.gov) - P2/3 | N=210 | Active, not recruiting | Sponsor: Instituto Grifols, S.A. | Suspended ➔ Active, not recruiting | Trial completion date: Sep 2023 ➔ Dec 2022 | Trial primary completion date: Jun 2023 ➔ Dec 2022

Enrollment closed • Trial completion date • Trial primary completion date

FORCE: Study of the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-polio Syndrome (clinicaltrials.gov) - P2/3 | N=210 | Suspended | Sponsor: Instituto Grifols, S.A. | Recruiting ➔ Suspended

Trial suspension

FORCE: Study of the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-polio Syndrome (clinicaltrials.gov) - P2/3; N=210; Recruiting; Sponsor: Instituto Grifols, S.A.; Trial completion date: Dec 2022 ➔ Sep 2023; Trial primary completion date: Jun 2022 ➔ Jun 2023

Clinical • Trial completion date • Trial primary completion date

Study to Evaluate the Safety and Efficacy of High Dose IVIG in Hospitalized Participants With Coronavirus Disease (COVID-19) (clinicaltrials.gov) - P2; N=100; Completed; Sponsor: Instituto Grifols, S.A.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP • PCR

Anti-SARS-CoV-2 Antibodies Within IVIg Preparations: Cross-Reactivities With Seasonal Coronaviruses, Natural Autoimmunity, and Therapeutic Implications. (PubMed, Front Immunol) - " 13 samples from 5 commercial IVIg preparations from pre-pandemic donors (HyQvia (Baxalta Innovations GmbH); Privigen (CSL Behring); Intratect (Biotest AG); IgVena (Kedrion S.p.A); and Flebogamma (Grifols S.A.) were blindly screened using a semi-quantitative FDA-approved and validated enzyme-linked immunosorbent assay (ELISA) (Euroimmun, Lubeck, Germany)... Pre-pandemic IVIg donors have either natural autoantibodies or pre-pandemic cross-reactive antibodies against antigenic protein fragments conserved among the "common cold" - related coronaviruses. The findings are important in: (a) assessing true anti-SARS-CoV-2-IgG seroprevalence avoiding false positivity in IVIg-receiving patients; (b) exploring potential protective benefits in patients with immune-mediated conditions and immunodeficiencies receiving acute or chronic maintenance IVIg therapy, and (c) validating data from a recent controlled study that showed significantly lower in-hospital mortality in the..."

Journal • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Study to Evaluate the Safety and Efficacy of High Dose IVIG in Hospitalized Participants With Coronavirus Disease (COVID-19) (clinicaltrials.gov) - P2; N=100; Active, not recruiting; Sponsor: Instituto Grifols, S.A.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Results of Grifols' AMBAR clinical trial published in Alzheimer's & Dementia: The Journal of The Alzheimer's Association (PRNewswire) - "Alzheimer's & Dementia: The Journal of the Alzheimer's Association...today has published the results of Grifols' AMBAR study....The findings of the AMBAR clinical trial demonstrate a delay in the cognitive and functional decline in AD patients when their plasma is replaced with albumin and immunoglobulin (plasma-derived proteins) following the process of plasma extraction, using the plasmapheresis technique."

P2/3 data • Alzheimer's Disease • CNS Disorders

Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens. (PubMed, Immunotherapy) - "For SARS-CoV-2, positive reactivity was observed at IVIG concentrations ranging from 100 μg/ml with Gamunex-C to 1 mg/ml with Flebogamma 5% DIF. Gamunex-C and Flebogamma DIF contain antibodies reacting against SARS-CoV-2 antigens. Studies to confirm the utility of IVIG preparations for COVID-19 management may be warranted."

Journal • Novel Coronavirus Disease

Study to Evaluate the Safety and Efficacy of High Dose IVIG in Hospitalized Participants With Coronavirus Disease (COVID-19) (clinicaltrials.gov) - P2; N=100; Not yet recruiting; Sponsor: Instituto Grifols, S.A.

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

How to select and manage the gamma-globulin therapy according to each different clinical entities considering tolerance, comorbidity and patient quality of life (ICA 2012) - Presentation time: 11.05.2012, 10:00-16:30; P=NA, N=106; 42% reported mild adverse effects in the first infusion with IVIG preparations 4% moderate adverse effects and 1.8% severe reactions; Of 65 patients with Flebogamma, 13 were switched to Privigen due to lower volume and timing of infusion, intense headache and progression of renal failure; One patient changed from Privigen to Flebogamma due to less tolerance

Clinical data • Immunology

Efficacy and safety study of IVIG in hospitalized subjects with COVID-19 Estudio de eficacia y seguridad de IGIV en sujetos hospitalizados con COVID-19 (clinicaltrialsregister.eu) - P2; N=100; Ongoing; Sponsor: Instituto Grifols, S.A

Clinical • New P2 trial

FORCE: Study of the Efficacy and Safety of Immune Globulin Intravenous (Human) Flebogamma® 5% DIF in Patients With Post-polio Syndrome (clinicaltrials.gov) - P2/3; N=210; Recruiting; Sponsor: Grifols Therapeutics LLC; Trial completion date: Jun 2021 ➔ Dec 2022; Trial primary completion date: Jan 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date

AMBAR (Alzheimer’s Management By Albumin Replacement) Phase 2B/3 Trial: complete clinical, biomarker and neuroimaging results (CTAD 2019) - P2/3; "The distribution of AEs over time showed an accumulation of events during the conventional TPE period with a progressive decrease during the LVPE period. Percentage of patients with infections was higher in patients treated with PE-A without IVIG (62.8%), not only than those treated with high dose and low dose albumin + IVIG (39.2 and 39.5%, respectively) but also than those in the placebo arm (41.8%)."

Biomarker • Clinical • P2/3 data • P2b data • FDG PET • MRI

Plasma exchange for Alzheimer's disease Management by Albumin Replacement (AMBAR) trial: Study design and progress. (PubMed, Alzheimers Dement (N Y)) - "...The study evaluates PE with different replacement volumes of therapeutic albumin (5% and 20% Albutein, Grifols), with or without intravenous immunoglobulin (Flebogamma 5% DIF, Grifols)...The study has been designed to demonstrate clinical efficacy, defined as slow decline of the patient's cognition and brain function. The sample size has adequate power to detect differences between any of the active treatment groups and the control group, as well as between the three active treatment groups combined and the control group."

Journal