An Open Study of the Safety and Pharmacokinetics of a Medicinal Product for Emergency Prevention of Ebola
Condition: Healthy
MeSH terms: Emergencies
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): GamEMab
Intervention type(s): Biological
Intervention description(s): drug for emergency prevention of Ebola based on recombinant monoclonal antibodies
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ebola; Ebola Virus Disease; Monoclonal antibody