Saint Claude, France

A Study of Dabrafenib Plus Cetuximab/Panitumumab With FOLFOX in the First Line of Therapy in People With Metastatic Colorectal Cancer

The purpose of the study is to evaluate the efficacy and toxicity of first-line FOLFOX with dabrafenib and cetuximab or panitumumab in patients with previously untreated metastatic inoperable colorectal cancer who have MSS and BRAF mutation.

A Safety and Pharmacokinetics Study of Complarate (Tocilizumab Biosimilar Solution) and Actemra® in Healthy Volunteers

Complarate (tocilizumab, solution) is being developed as a biosimilar to the drug Actemra®, a solution for subcutaneous injection. Tocilizumab is a recombinant humanized monoclonal antibody to the human interleukin-6 (IL-6) receptor from the immunoglobulin G1 (IgG1) subclass. Tocilizumab binds to and inhibits both soluble and membrane IL-6 receptors (sIL-6R and mIL-6R). This I phase study is aimed to compare the pharmacokinetics and safety of the drugs Complarate and Actemra® after their single subcutaneous administration to healthy volunteers at a dose of 162 mg. The study included healthy volunteers aged 18-45 years at the time of signing the informed consent form. The study included a screening period, single administration of study/comparator drug and a follow up period. Allocation of patients to treatment groups was carried out by randomization in a ratio of 1:1 to the study drug and comparator drug. 256 patients (128 to the study drug group and 128 to the comparator drug group) are being randomized.

An Efficacy and Safety Study of GNR-086 (canakinumab Biosimilar) and Ilaris® in Patients with Adult-onset Still's Disease

GNR-086 is being developed as a proposed biosimilar to Ilaris®, a lyophilisate for the preparation of a solution for subcutaneous administration. Canakinumab is a fully human monoclonal antibody of the immuniglobulin G1 (IgG1(kappa)) isotype that binds specifically and with high affinity to interleukin-1β (IL-1β). Canakinumab, by binding to human IL-1β, blocks the interaction of this cytokine with its receptors, thereby functionally neutralizing the biological activity of this cytokine, without preventing either the binding of the natural inhibitor IL-1Ra, or the binding of IL-1α to IL-1 receptors. IL-1β is recognized as one of the main pro-inflammatory cytokines in various inflammatory conditions. This III phase study is aimed to compare the efficacy, safety and immunogenicity of GNR-086 and Ilaris®. The study will enroll patients with the confirmed diagnosis of adult-onset Still's disease in accordance with the classification criteria of Yamaguchi M. et al. (J. Rheumatology, 1992), and the duration of the disease at least 2 months before inclusion into the study. 148 paitnts will be randomised 2:1 to receive either GNR-098 or Ilaris®. Participants will receive canakinumab 4 mg/kg suncutaneously every 4 weeks for 24 weeks following the study extension.

Bacteriophages in Addition to Antibiotics for the Treatment of Patients with Infective Endocarditis

Given the steady increase in antibiotic resistance in bacteria and the decreasing number of new antibacterial drugs, phage therapy may prove to be a revolutionary safe approach, especially attractive for the following reasons: phages are easily isolated from a diverse environment and affect only the pathogenic cell without affecting neighbouring cells, they are able to successfully target bacteria with multiple resistance and, therefore, can potentially replace antibiotic therapy. A feature of bacteriophages is their high specificity, which at the same time may be a limitation for their widespread use in the absence of knowledge about bacterial sensitivity. The above-mentioned suggests the possibility of using a cocktail of bacteriophages selected taking into account the expected spectrum of pathogens and their sensitivity. A similar strategy was first developed by Zurabov F. (2021), who proposed adaptive phagotherapy for the prevention of recurrent nosocomial pneumonia, the specificity of which was the selection of bacteriophages not for an individual patient, but for the entire spectrum of bacteria circulating in the intensive care unit with continuous clinical and microbiological studies with monitoring of efficacy. Based on the collection of hospital bacteria of 66 antibiotic-resistant strains, a complex preparation of bacteriophages for inhalation administration was developed. The study included 83 patients in chronic critical condition with recurrent pneumonia in whom high safety and efficacy of the new approach were convincingly demonstrated. The undeniable advantage of phagotherapy is its targeted effect on pathogenic bacteria without affecting the microbiota, and therefore the absence of such side effects as mucous membrane candidiasis, antibiotic-associated diarrhoea, pseudomembranous colitis, etc. A number of studies have demonstrated the absence of any side effects, which is probably due to the fact that bacteriophages are natural inhabitants of the environment in harmony with humans. A number of studies have demonstrated the absence of any side effects, which is probably due to the fact that bacteriophages are natural inhabitants of the environment, harmoniously co-existing with humans. A separate advantage of phage therapy is the ability of several types of phages to affect the same bacterial strains, which minimises the risk of developing resistance to bacteriophages. The success of phagotherapy in patients with IE has been demonstrated in only a small number of experimental and clinical studies. The treatment with BF does not yet have a strong evidence base from randomised clinical trials, but the available clinical data from a variety of pathologies (skin, soft tissue and joint infections, implanted intracardiac devices), suggest that phage therapy may be an effective adjunct to conventional antibiotic therapy or even as a stand-alone treatment. Since currently the most common pathogens of IE are staphylococci, in particular S. aureus, the largest number of studies on the use of BF has been noted in this etiological affiliation of IE. As S. aureus-induced IE is more often associated with an unfavourable course, this is what prompted the search for new approaches to therapy, and the first studies on the use of BF represented a salvage therapy, especially in the context of multidrug resistance. In general, no more than 10 modern experimental and clinical studies on the possibility of using bacteriophages in staphylococcal IE are presented, including 3 separate clinical observations and one description of a series of 13 cases of IE. In an experimental rat model of S. aureus MSSA IE showed high efficacy of combined therapy with flucloxacillin with phage cocktail (intravenous form) with respect to vegetation sterility in 9/12 rats. Similar success was obtained in the experiment of IE caused by S. aureus MRSA when treated with a combination of bacteriophages with vancomycin. This type of pathogen is characterised by a high incidence of antibiotic resistance, which makes the use of BF in this group of patients particularly useful. In 2019 was one of the first to present a clinical observation of a 65-year-old patient with non-ischaemic dilated cardiomyopathy and IE of intracardiac device, uncontrolled course of infection against the background of repeated change of antibiotic therapy. The use of intravenous anti-staphylococcal cocktail AB-SA01 for 28 days 2 times a day in combination with antibiotic therapy allowed to achieve complete control of infection with subsequent heart transplantation [30]. In 2019 was demonstrated a similar observation of successful application of intravenous anti-staphylococcal cocktail AB-SA01 for 14 days twice a day in a patient with IE of S. aureus prosthetic valve and ineffectiveness of antibiotic therapy. Combined treatment with BF allowed to achieve complete recovery of the patient. The efficacy and safety of intravenous anti-staphylococcal cocktail AB-SA01 for 14 days twice a day in 13 patients with severe S.aureus infections, including IE. The researchers did not note any side effects, but the conclusion on the efficacy of therapy required further studies. Pneumococcal bacteriophage Cpl-1 was investigated in an experiment on rats with IE caused by Str. pneumoniae, demonstrating rapid blood sanitation and reduction of pathogen concentration in vegetations. Also, researchers investigated the efficacy of phage therapy in IE caused by Pseudomonas aeruginosa in an experiment. The combination of BF and ciprofloxacin caused rapid sanitation of vegetations. Among the dangerous and difficult to treat pathogens of IE, it is necessary to highlight the representatives of enterococci - Ent. faecalis and Ent. faecium, characterised by the ability to develop multidrug resistance, which has increased markedly over the last 10 years. According to some data, the incidence of enterococci in fatal IE can reach 97%. A distinctive feature of enterococci is their ability to form biofilms, which significantly complicates the therapy of IE. BF has a unique ability to destroy biofilms based on the layer-by-layer penetration of BF into deeper layers of vegetation. In an experiment proved that BFs are able to penetrate vegetations, including in IE caused by E. faecalis. There have been no clinical studies on the efficacy of BF in enterococcal IE. In an experiment on modelling vegetations from human blood ex vivo, another study showed the possibility of synergy of BF with antibacterial drugs (daptomycin, ceftraroline), including the restoration of sensitivity of enterococci to antibacterial drugs. Thus, the treatment of IE, even with a known etiology, is a global challenge. Considering the fact that IE is often found among comorbid, elderly and debilitated patients, with high cardiac surgery perioperative risk, as well as the high frequency of IE with unidentified etiology not because of association with hard-to-cultivate pathogens, but because of low concentration of typical pathogen in blood due to previous antibiotic therapy, prolonged effective antibiotic therapy is often the only safe solution in such cases. Taking into account the limited spectrum of effective antibacterial drugs, it is extremely important to study the efficacy and safety of phagotherapy in combination with antibacterial drugs in IE. The most optimal is the study of phagotherapy in the form of phage cocktail to the most common typical pathogens of IE with application at the initial stages of treatment as part of empirical antibacterial therapy. It is assumed that such an early start of effective treatment will avoid the development of resistance to antibacterial drugs and lead to rapid relief of IE activity with subsequent transfer of patients to outpatient treatment regimes. The advantage of the presented treatment algorithm is the possibility to cover all patients with IE before the etiological affiliation is established, which will make it possible to obtain the treatment effect already at the early stages of therapy.

Safety and Efficacy of MILEP Versus Standard EEP

Efficacy, Safety, and Tolerability of 4-MUST Tablets in Chronic Cholecystitis and Biliary Dyskinesia

Efficacy and Safety of Ranquilon in Patients With Anxiety Disorders Due to Neurasthenia and Adaptation Disorders

Study to Evaluate the Efficacy and Safety of Using Different Doses of Graminidin With Anesthetic for the Treatment of Acute Infectious-inflammatory Diseases of the Pharynx in Comparison With Septolete Total, Lozenges

Predictors of Poor Prognosis in HFpEF

Heart failure with preserved ejection fraction (HFpEF) is a serious condition with an unfavorable prognosis. The investigators aimed to evaluate in patients with HFpEF: - the prognostic significance of standard resting hemodynamic parameters compared to key cardiac reserves; - the prognostic significance of clinical parameters (sex, age, NYHA class, extra-cardiac diseases, therapy); - the prognostic significance of biological markers of hemodynamic stress and biomarkers of inflammation and fibrosis; - to identify independent predictors of adverse prognosis of HFpEF.

Safety, Tolerability, and Pharmacokinetic Parameters of Increasing Doses of Ingavirin Forte, Capsules, During Single and Subsequent Multiple Oral Administration in Healthy Volunteers