An Open Study of the Safety and Pharmacokinetics of a Medicinal Product for Emergency Prevention of Ebola — 03-AT-2017  

Healthy Clinical Trial

Official title: An Open, Dose Escalation Safety and Pharmacokinetics Study of the Medicine for Ebola Fever Emergency Prevention Based on Monoclonal Recombinant Antibodies With a Single Application in 3 Groups of Healthy Volunteers

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Emergencies
• Healthy

• NCT number: NCT03428347
• Study type: Interventional
• Source: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
• Status: Completed
• Phase: Phase 1
• Start date: March 12, 2018
• Completion date: December 29, 2018