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

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 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.

Study Overview

• Status: Unknown
• Conditions: Whooping Cough
• Intervention / Treatment: Other: Placebo; Biological: Vaccine GamLPV

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • Infectious Disease Clinical Hospital No. 1 of the Moscow Healthcare Department
    • Contact: Marina Rusanova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female aged 18 to 40 (inclusively);
2. 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);
3. BMI froim 18 to 30 kg/m2 (inclusively);
4. Consent to use of reliable birth control methods during the test period and for 3 months thereafter (a condom with spermicide);
5. Signed FactSheet and Informed Consent to Participation in the Study.
6. No specific IgM to the pertussis agent (negative IFA finding according to manufacturer's instruction for the anti-pertussis antibody detection test system);
7. Specific anti-pertussis IgG ≤ 45 EU/ml
8. No B.pertussis DNA in nasopharyngeal swabs (based on RT-PCR).

Exclusion Criteria:

1. Whooping cough in past medical history
2. Vaccination against whooping cough over the past decade
3. Any other anti-infective immunization during last year
4. 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
5. Vaccine-associated diseases or clinically significant vaccinal reactions in medical history
6. Clinically significant abnormal laboratory values at the discretion of the investigator
7. Positive results of HIV, hepatitis B or C
8. Use of narcotic drugs and/or a history of drug/alcohol abuse
9. Allergic diseases in medical history (in particular drug reaction and food allergy)
10. 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
11. Current participation in any other clinical trial
12. Inability to adhere to the protocol
13. Acute infectious diseases within 4 weeks prior to screening
14. Wheezing on the results of peakflowmetry
15. Significant ECG changes
16. Pregnancy or lactation (for female volunteers)
17. Systolic blood pressure less than 90 mmHg or over than 130 mmHg; diastolic blood pressure less than 60 mmHg or over 90 mmHg
18. Heart rate less than 60 bpm or more than 90 bpm
19. Specific anti-pertussis IgG ≥ 45 EU/ml
20. The presence of B.pertussis DNA in nasopharyngeal swabs (based on RT-PCR).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation
• Investigators: Principal Investigator: Marina Rusanova, Infectious Disease Clinical Hospital No. 1 of the Moscow Healthcare Department

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Anticipated): May 29, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 29, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: antibody response; Immunological factors; whooping cough; Bordetella pertussis; Live vaccine; cell immune response
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Whooping Cough; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: GamLPV-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No