PNEUMONIOS: Phase III Multi-centre Clinical Trial

Inspiration

Postbiotics are new classes of natural molecules released during human microbiome’s metabolic activities. These metabolites regulate host-microbe interaction and intestinal homeostasis, being beneficial for our health. Because of their intrinsic low toxicity and immunomodulatory properties, they represent a novel solution for a number of medical applications, in particular for COVID-19 infected individuals.

Name of entity

POSTBIOTICA S.R.L

What it does

Postbiotica is a novel biopharmaceutical company engaged in the discovery and development of postbiotics. In particular, Postbiotica has developed a new food supplement product, FOSBIOTICimm. FOSBIOTICimm, is a new postbiotic-based food supplement produced by Postbiotica which contains an active ingredient, Fermented fructo-oligosaccharide (FOS) or ‘ImmunoFOS.’ Of special importance for COVID-19 infections, FOSBIOTICimm does not contain live bacteria which could otherwise be dangerous for immunocompromised individuals. FOSBIOTICimm modulates the inflammatory response of epithelial and immune cells to pathogens, favoring the maintenance of a proficient epithelial barrier. FOSBIOTICimm can also increase the production of the anti- inflammatory cytokine IL-10 by peripheral blood mononuclear cells, while keeping IL-12 unaffected or slightly reduced. This process allows for the control of inflammatory responses without affecting the initiation of a protective immune response since IL-12 is a potent cytokine that enhances the cytotoxic activity of T lymphocytes and resting natural killer cells. As a consequence, FOSBIOTICimm can protect from an endotoxin shock in preclinical mouse models of lipopolysaccharide administration.

How I built it

Thanks to PBtech®, Postbiotica designed and developed a new immunomodulatory Postbiotic (PB-600F/ImmunoFOS) that could control an overt inflammation and increase barrier properties of mucosal surfaces. As a result, hosts could be protected from infection-related conditions. FOSBIOTICimm, is a new food supplement formulated by Postbiotica containing the active ingredient ImmunoFOS®.

Phase

Clinical Trial Phase III

Study design and study duration

COVID-19 is a highly infective virus with a mortality rate associated with age and comorbidities (including cardiovascular disorders, diabetes, chronic respiratory disorders, hypertension and cancer). One of the major causes of deaths is complications related to the immunopathology of pneumonia. It is thought that COVID-19 once inside the human respiratory tract, it infects and multiplies in cells lining the airway, causing damage that activates the immune system. For reasons that are not yet clear, some people, especially the elderly with comorbidities, may have impaired immune systems that undergo an exaggerated inflammatory response. This triggers an overproduction of inflammatory mediators leading to a cytokine storm often associated with a flood of immune cells into the lung. Given the capacity of FOSBIOTIC to control inflammation without affecting the initiation of an immune response and to protect epithelial barriers, we want to evaluate whether its administration to confirmed COVID-19 infected individuals reduces their risk to develop morbidities and in particular the access to intensive care units. We believe that FOSBIOTIC could be used to prevent exaggerated inflammatory responses and to protect against the cytokine storm associated with COVID-19 infection thus reducing the cases of intensive care need, also demonstrating to be cost-effective. PNEUMONIOS is a multi-center, controlled, 1:1 randomized, double blind, trial of FOSBIOTICimm versus placebo in patients with confirmed COVID-19 infection in symptomatic patients. FOSBIOTICimm administration duration will last a maximum of 30 days. The time of permanence of patients in a specific state of their disease will be recorded and incorporated in a composite primary outcome, with clinical recovery and death accounted for in the competitive risk analysis. Specifically, the following states are defined: 0 = oligo symptomatic COVID+; 1 = hospitalized; 2 = non-invasive assisted ventilation; 3 = invasive ventilation (ICU); 4 = death; 5 = clinical recovery; 6 =viral recovery. Out-patients will record their symptoms for duration and intensity on a diary. Clinicians will record whether the patients will need admission to ICU, the length of stay and whether they are recovered from the infection.

Description of study treatment/product/intervention

Patients will be enrolled consecutively. In case of self-administration, patients will be asked to record daily in a diary their symptoms for duration and intensity as well as concomitant medications taken. Clinicians will record whether the patients will need hospitalization and/or admission to ICU, the length of stay and whether they are recovered from the infection.

Objectives

Primary endpoint: To demonstrate that FOSFBIOTIC administration in addition to the standard of care as compared to the standard of care alone is associated to lower rate of severe or critical infection or acute respiratory distress syndrome (ARDS) within the first 14 days after randomization in patients with a diagnosis of COVID-19 infection. Secondary objectives: To evaluate the need for ICU admittance and the total ICU length of stay in COVID-19 infected patients treated or not with FOSBIOTIC. To analyse all-cause mortality rate in the FOSBIOTIC experimental group versus control group. To analyze Sequential Organ Failure Assessment (SOFA) scores at baseline and on study days 1, 3, 7, 14, 21 and 28 To evaluate Organ support, according to the number of days within the first 28 days after enrollment when patients do not receive specific forms of support To evaluate duration of clinical symptoms. Exploratory endpoints: To evaluate the plasma level of cytokines (eg IL-10, IL-6, etc) and IgA in FOSBIOTIC experimental group versus control group.