Assessment of the Clinical Effect of Dialyzable Leukocyte Extracts in Individuals With Acute Respiratory Infection (Suspected or Confirmed Cases of COVID-19) (FUTURE-T)

Dialyzable Leukocyte Extract (DLE) (Transferon oral®) is a dialyzed extract obtained from human leukocytes. Its active ingredient is a complex mixture of low molecular weight peptides obtained from dialysis (12 kDa), and subsequent ultrafiltration (10 kDa) of lysed leukocyte and platelet concentrates. This product is manufactured by Laboratory of Scientific Research (Pharma-FT) at the Nacional School of Biological Sciences (ENCB), National Polytechnic Institute (IPN) using a patented method in Mexico (MX/a/2011/013852), USA (US9328152B2), EU (EPA-126128), Canada (2860260), Peru (000969-2014/DIN) and Colombia (14138326).

DLE is a complex drug, the active principle is multiple peptide units. Thus, DLE cannot be fully characterized, requiring the application of analytical techniques that can describe the overall behavior of all of its components (peptide polydispersity).

Two orthogonal techniques have been used to determine the molecular weight of the peptide components of DLE based on their migration through a polymer matrix. The molecular weight of 10 kDa was determined by polyacrylamide gels electrophoresis under denaturing conditions (SDS-PAGE), while a molecular weight lower than 15 kDa was determined by molecular exclusion chromatography.

The peptide nature of DLE has been demonstrated using an aminogram method. This method includes the acidic hydrolysis of the peptide components until free amino acids are obtained, which are derivatized and identified based on the retention time of an amino acid standard using reverse phase chromatography (RP-UPLC). Additionally, the peptides of this drug were determined to be highly soluble by RP-UPLC coupled to UV, while mass spectometry, coupled to RP-UPLC, exhibited consistent ionization patterns.

Non-clinical and clinical studies relevant to this research. Experimentally, in a murine model of virus infection, administration of DLE showed a decrease in serum concentrations for TNF and IL-6, accompanied by an increase of IFN. In humans, viral etiology is responsible for 90-95% of cases of respiratory tract infections. The common viruses involved in respiratory diseases are rhinoviruses (∼50%), coronaviruses (∼10%), adenoviruses, respiratory syncytial virus, influenza, and parainfluenza viruses (which generally add up between 10% to 15%), human metapneumovirus (<5 %). The first evidence that DLE might have a therapeutic effect in respiratory infections arose from the analysis of a series of cases (36 adults and 63 children) with allergic rhinitis who received DLE in addition to the standard treatment. 11% of adults and 25.4% of children reported a decrease in the frequency of respiratory infections. Similarly, in a series of 70 adults and 54 children with persistent moderate asthma who received treatment with DLE as adjuvant therapy, 44% of adults and 31% of children reported a decrease in the frequency of respiratory infections, in addition to the improvement of allergic symptoms. In a study of 52 individuals, the effectiveness of DLE was evaluated by reducing the severity and frequency of infectious symptoms. That study showed a decrease in the frequency and in the severity of the infectious respiratory symptoms (77.1%) in pediatric patients. In comparison, 82.4% of adults decrease the frequency and/or diminish the severity of infectious respiratory symptoms. In a clinical follow-up of pediatric patients with sepsis to whom DLE was added to the standard treatment decrease in C-reactive protein levels, reduction in the neutrophil count at 72 hours after hospitalization, and an increase in the survival rate of 30% was reported.