A Phase 1/2 Clinical Trial of a GamLPV, a Live Intranasal Bordetella Pertussis Vaccine

Study Overview
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Brief Summary
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The study should be leaded as a randomized double-blind placebo-controlled comparative research of potency and safety of a GamLPV, a live intranasal Bordetella pertussis vaccine, using two dosing schedules and methods of application in healthy human volunteers. The study contains three periods: screening, inpatient hospitalization and follow-up.

Detailed Description
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Subjects are divided into two groups - 25 volunteers in each group. Group 1 will receive vaccine/placebo by drop method. Group 2 will receive vaccine/placebo with nasal actuator. After 60 days both groups will repeatedly receive the same dose of vaccine/placebo by the same methods of application. In each group there are 5 volunteers given placebo. Monitoring examination of volunteers is carrying out during 60 days after first and second vaccination. Each group (25 persons) shall be divided into three cohorts (5, 7 and 13 persons). The arm that will receive the drug/ placebo by the dripping method comprises cohorts 1, 3, and 5, and the arm that will receive the drug using the applicator comprises cohorts 2, 4, and 6. Initially, the first and second cohorts (of 5 volunteers each) will be included into the study, respectively. The main purpose of this study is selection of methods of applications and dosing schedules of GamLPV, a live intranasal Bordetella pertussis vaccine.

Official Title
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Randomized Double-blind Placebo-controlled Comparative Research of Potency and Safety of a GamLPV, a Live Intranasal Bordetella Pertussis Vaccine, Using Two Dosing Schedules and Methods of Application in Healthy Human Volunteers

Conditions
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Whooping Cough

Intervention / Treatment
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* Biological: Vaccine GamLPV
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 to 40 (inclusively); Healthy verified diagnosis according to standard clinical, laboratory and instrumental examination methods (no somatic disorder of the gastro-intestinal tract (GIT), liver, kidneys, cardiovascular system (CVS), infectious, hematological diseases, cancers (including if the preliminary standard clinical laboratory tests did not reveal any diseases); BMI froim 18 to 30 kg/m2 (inclusively); Consent to use of reliable birth control methods during the test period and for 3 months thereafter (a condom with spermicide); Signed FactSheet and Informed Consent to Participation in the Study. No specific IgM to the pertussis agent (negative IFA finding according to manufacturer's instruction for the anti-pertussis antibody detection test system); Specific anti-pertussis IgG ≤ 45 EU/ml No B.pertussis DNA in nasopharyngeal swabs (based on RT-PCR). Exclusion Criteria: Whooping cough in past medical history Vaccination against whooping cough over the past decade Any other anti-infective immunization during last year Any medical condition (renal diseases, hepatic disorders, haematological malignancies, malignant neoplasms and other diseases) which, in the opinion of the investigator, might interfere with the evaluation of the study objectives Vaccine-associated diseases or clinically significant vaccinal reactions in medical history Clinically significant abnormal laboratory values at the discretion of the investigator Positive results of HIV, hepatitis B or C Use of narcotic drugs and/or a history of drug/alcohol abuse Allergic diseases in medical history (in particular drug reaction and food allergy) The subject has donated blood/plasma or suffered from blood loss of at least 450 ml (1 unit of blood) within 6 weeks prior to screening Current participation in any other clinical trial Inability to adhere to the protocol Acute infectious diseases within 4 weeks prior to screening Wheezing on the results of peakflowmetry Significant ECG changes Pregnancy or lactation (for female volunteers) Systolic blood pressure less than 90 mmHg or over than 130 mmHg; diastolic blood pressure less than 60 mmHg or over 90 mmHg Heart rate less than 60 bpm or more than 90 bpm Specific anti-pertussis IgG ≥ 45 EU/ml The presence of B.pertussis DNA in nasopharyngeal swabs (based on RT-PCR).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Present clinical trial is a randomized placebo-controlled study for selection of dosing schedules and application methods of GamLPV, a live intranasal Bordetella pertussis vaccine. The study is blinded for volunteers.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 Drop method<br>Group 1 will receive vaccine/placebo by drop method. | Biological: Vaccine GamLPV<br>* live intranasal vaccine for whooping cough prevention<br>* Other names: live intranasal Bordetella pertussis vaccine;Other: Placebo<br>* Placebo<br>|
| Experimental: Group 2 Nasal actuator<br>Group 2 will receive vaccine/placebo with nasal actuator. | Biological: Vaccine GamLPV<br>* live intranasal vaccine for whooping cough prevention<br>* Other names: live intranasal Bordetella pertussis vaccine;Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| methods of applications | selection of methods of applications of GamLPV, a live intranasal Bordetella pertussis vaccine (drop method or nasal actuator is important for vaccination) | the total Time Frame is 140 days after the vaccination | 
| dosing schedules | selection of dosing schedules of GamLPV, a live intranasal Bordetella pertussis vaccine (repeated administration in 60 days) | the total Time Frame is 140 days after the vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| specific antibody response to B.pertussis | Evaluation of the antibody response after single and double intranasal vaccine administration in healthy volunteers with nasal actuator and by drop method compared to placebo. Detection of antibody level (IgG and IgA) in blood serum and nasopharyngeal aspirates in healthy human volunteers by ELISA. | the total Time Frame is 140 days after the vaccination | 
| cell immune responses to B.pertussis | Evaluation of cell immune response parameters after single and double intranasal vaccine administration in healthy volunteers with nasal actuator and by drop method compared to placebo. Detection of induced INF- γ and IL-17 quantity in PBMC supernatant (by ELISA). | the total Time Frame is 140 days after the vaccination | 
| dynamics of bacteria generation in nasopharynx of human volunteers | Evaluation of bacterial load in oropharynx/nasopharynx over time after single and double intranasal vaccine administration in healthy volunteers with nasal actuator and by drop method (B.pertussis DNA detection by RT-PCR method in nasopharyngeal swabs) | the total Time Frame is 140 days after the vaccination | 
| Comparative assessment of immunogenicity | Comparative analysis of GamLPV immunogenicity after single and double intranasal vaccine administration in healthy volunteers with nasal actuator and by drop method (by antibody response evaluation by ELISA) | the total Time Frame is 140 days after the vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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whooping cough, Bordetella pertussis, Live vaccine, Immunological factors, antibody response, cell immune response