An Open Study of the Safety and Pharmacokinetics of a Medicinal Product for Emergency Prevention of Ebola
An Open Study of the Safety and Pharmacokinetics of a Medicinal Product for Emergency Prevention of Ebola
This Phase I clinical trial was developed to study drug safety, tolerability, and
 pharmacokinetics of the medicine for Ebola fever emergency prevention based on monoclonal
 recombinant antibodies in single use in healthy volunteers with a dose escalation. A
 consecutive recruitment of people who signed the Informed Consent Form into three groups of
 volunteers with different drug doses is made according to the volunteers' screening results.
 The total number of volunteers receiving the drug will be not less then 25 people.The purpose
 of this study is to assess safety, tolerability, and pharmacokinetics of a medicine for Ebola
 fever emergency prevention based on monoclonal recombinant antibodies in a single dose in
 healthy volunteers.
The results of the screening of volunteers who signed the informed consent Form, is a
 sequence set in three groups of volunteers with different doses of the drug, the total number
 of volunteers who received the drug will be at least 25 people.

 Taking into account the fact that for the first time the drug is studied on people, initially
 five volunteers will be hospitalized. Their dose of the studied medicine will be 1.4 mg/kg of
 weight. After confirmation of safety based on observation results on the 60th day of the
 study, the investigation will continue with the participation of five more volunteers. Safety
 will be studied on these five volunteers with a single use of dose of 7 mg/kg of weight.

 After an intermediate safety assessment on the 60th day, 15 more volunteers will be included
 in the study. They will get the medicine with the dose of 14 mg/kg of weight.

 If necessary, understudies in an amount of not more than 4 people may be included. Volunteers
 are replaced before the injection of the medicine. If a volunteer got the medicine, he could
 not be replaced.

 After evaluating the safety analyzes' intermediate results (blood test and blood chemistry,
 urinalysis, immunological safety, clinical evaluation of general health status) obtained on
 day 60 of the study, the Researcher, in agreement with the Ethics Committee, makes a decision
 to include the second group (five people) to study the drug at a dosage of 7 mg/kg of weight.
 After the evaluation of intermediate safety results on the 60th day of the study of
 volunteers from the second group, 15 more volunteers will be included in the study. After the
 intermediate evaluation of safety on the 60th day of study, 15 more volunteers will be
 included in the study and get the medicine in a dose of 14 mg/kg of weight. Wherein the third
 part of volunteers is planned to be included consistently: in the beginning 5 volunteers will
 be included and after the intermediate safety evaluation on the 28th day the rest 10
 volunteers will be included in the study.

 The safety and tolerability assessment will be based on the registration of adverse events
 during the study. Changes in instrumental (ECG) and laboratory indicators (blood test and
 blood chemistry, blood coagulation system indicators, urinalysis, immunological status),
 dynamics of vital signs (blood pressure, heart rate, body temperature) will be also
 evaluated.

 Pharmacokinetic parameters will be calculated by a model-independent method. Immunological
 methods (ELISA) will be used for studying the level of specific antibodies and the duration
 of their circulation in the human body.

 Sampling of biological material involves:

 Urinalysis: at screening, before administration of the drug after 48 hours and on 7, 10, 14,
 21, 28, 45, 60 and 90 days of the study; urine samples for a pregnancy test taken at
 screening and on the day of hospitalization (in addition to volunteers women).

 to define security settings (General clinical and biochemical** blood tests, including a
 study of the coagulation system): at screening, before dosing, 48 hours, and 7, 10, 14, 21,
 28, 45, 60 and 90 days of the study; immune status***- the drug, 7, 10, 14, 21, 28, 45, 60
 and 90 days of the study; will also be determining the level of specific antibodies to the
 drug (with detection with the determination of class, subclass, immunoglobulins and
 assessment of their functional activity) is the drug, 7, 10, 14, 21, 28, 45, 60 and 90 days
 of the study; **biochemical blood analysis includes a determination of: total protein, urea,
 creatinine, aspartataminotransferase (AST), alanine aminotransferase (ALT), alkaline
 phosphatase, total bilirubin, glucose, cholesterol, creatine phosphokinase, CRP,
 concentration of electrolytes (sodium, potassium), coagulation include: PI+, INR, APTT,
 fibrinogen.

 *** evaluation of the immunological status includes: determining the number and relative
 content of subpopulations of T - and b-lymphocytes (CD3, CD 4, CD 8, CD 16, CD19), phagocytic
 activity of white blood cells, immunoregulatory index, content of serum immunoglobulins major
 classes (A, M, G, E), circulating immuno complexes, the detection of antibodies to the mouse
 immunoglobulin, the content of anti-inflammatory cytokines (TNF-α, ИЛ1, IL-6, IFN-γ).

 Blood samples for testing for hepatitis b and C, HIV and syphilis will be taken once at
 screening visit.

 In addition there will be samples of whole blood for analysis of pharmacokinetic parameters:
 before drug administration, through 1, 4, 8, 24, 36, 48 and 96 hours after drug
 administration, and 7, 10, 14, 21, 28, 45, 60 and 90 days study.
Inclusion Criteria:

 -  men and women aged 18 to 45 years;

 -  written informed consent;

 -  consent to use of effective contraception methods during the whole period of
 participation in the study; (using one of the following methods: abstinence, condoms
 (male or female with or without spermicide), diaphragm or cervical cap with a
 spermicidal tool, intrauterine device);

 -  body mass index (BMI) is 18.5 ≤ BMI ≤ 30;

 -  absence of acute infections/exacerbations of chronic at the time of participation in
 the study and for 7 days before initiation of therapy;

 -  absence of allergic disease severe disease (anaphylaxis, angioedema, polymorphic
 exudative eczema, serum sickness);

 -  no history of severe complications in a previous application of immunobiological
 preparations;

 -  lack of history, but also according to screening tests, pathology of the
 gastrointestinal tract, liver, kidneys, cardiovascular system, Central nervous system,
 musculoskeletal, urogenital and endocrine systems that can influence the evaluation of
 the results of the study;

 -  negative pregnancy test blood or urine (for women of childbearing age) not more than
 24 hours before receiving the first dose of study drug;

 -  negative tests for HIV, hepatitis b and C, syphilis;

 -  negative urine test for drug traces;

 -  negative test for alcohol content in breath;

 -  absence of malignant blood diseases;

 -  absence of malignant tumors;

 -  negative allergological study on the epithelium and the proteins of the mouse.

 -  anti-mouse antibody titer less than 1:500;

 -  indicators of the General analysis of blood, biochemical analysis of blood total IgE
 at screening within the normal values.

 *( will be provided normal reference values of the laboratory performing the study)

 -  no history of previous vaccination against Ebola, including during clinical studies

 Exclusion Criteria:

 -  volunteer participation in any other clinical trial within the last 90 days;

 -  respiratory symptoms in the last 3 days;

 -  treatment with steroids for the last 10 days (excluding preparations for intranasal
 administration and topical application);

 -  allergic reactions to proteins/epithelium of the mouse in history or about the results
 of laboratory studies on the screening, the titer of anti-mouse antibodies according
 to the study of 1:500 and more; introduction immunoglobulins or other blood products
 within the last 6 months;

 -  treatment with immunosuppressive drugs and/or immunomodulators within 6 months prior
 to the study;

 -  the use of other drugs based on murine monoclonal antibodies in history;

 -  regular past or current use of narcotic drugs;

 -  pregnancy or breast-feeding;

 -  systolic blood pressure less than 100 mm of mercury.St. or above 139 mm Hg.St;
 diastolic blood pressure less than 60 mm of mercury.St. or higher 90 mm. Hg.St.; heart
 rate less than 60 beats/min or more than 90 beats/min;

 -  aggravation of allergic diseases, the presence of anaphylactic reactions or angioedema
 in history;

 -  allergic reactions to the drug components;

 -  the presence of comorbid disease that may influence the assessment of the research
 results: active tuberculosis, chronic diseases of the liver and kidneys, expressed
 violations of function of thyroid gland and other endocrine system diseases
 (diabetes), severe diseases of the hematopoietic system, epilepsy and other diseases
 of the Central nervous system, myocardial infarction in anamnesis, myocarditis,
 endocarditis, pericarditis, ischemic heart disease, autoimmune disorders, severe
 chronic diseases that require hospital observation, and other diseases according to
 the researcher, will not allow the volunteer to participate in the study or may
 influence the research and/or its results (including the valuation of security);

 -  donating blood (450 ml blood or plasma, and more) in less than 2 months before the
 study;

 -  receiving history more than 5 units (0.25 l of ethanol) of alcohol per week;

 -  Smoking more than 10 cigarettes per day;

 -  planned hospitalization and/or surgical intervention during participation in the
 study.