A Phase I Clinical Study of a GamLPV, a Live Intranasal Bordetella Pertussis Vaccine

A Phase I Clinical Study of a GamLPV, a Live Intranasal Bordetella Pertussis Vaccine; A Randomized Placebo-controlled Dose-escalating Study of Single-use GamLPV Safety and Tolerability in Healthy Human Volunteers

The study contains three periods: screening, inpatient hospitalization and follow-up. And should be leaded as a randomized placebo-controlled study with in chain order enrolled volunteers and dose escalating.

Study Overview

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

Detailed Description

After screening, verifying of inclusion/exclusion criteria and signing of informed consent statement volunteers will be directed in a hospital and hospitalized in individual boxes.

Vaccine (GamLPV) or placebo will be administered to groups of volunteers. Each group includes 12 individuals. The study is dose-escalating, so there will be 3 groups.

Group 1: 9 individuals will be vaccinated intranasally with 2,5*108 bacteria (CFU), 3 individuals will get placebo.

Group 2: 9 individuals will be vaccinated intranasally with 109 bacteria cells(CFU), 3 individuals will get placebo.

Group 3: 9 individuals will be vaccinated intranasally with 4*109 bacteria cells(CFU), 3 individuals will get placebo.

On the third day volunteers will be discharged from hospital. 4 visits will be held during outpatient observation- on 8, 15, 29 and 60 days after administration - for physical examination and laboratory assessment. Beside that it would be suggested to volunteers to extend a deadline of participation in the clinical study until 150-th day.

For each dosing group the consecutive inclusion of volunteers with the intermediate evaluation of the safety parameters is stipulated. The group (12 people) is divided into two parts. Originally the first part (5 volunteers) is included in the study. Randomization will be performed by choosing the envelope with the randomizing number at the day of hospitalization. The volunteer will be given either the investigating laboratory specimen or placebo. The researcher includes in the study the 2nd part of the group (7 people) after the evaluation of the intermediate results of the safety analyses (total blood count, biochemical analysis, urinalysis, general examination of a patient). The researcher compiles the intermediate report with the analysis of the endurance of the investigating dose of the preparation after the evaluation of the intermediate safety results. The criterion of the endurance and the dose safety will be at first the absence of serious undesirable phenomena and clinically important shifts of the laboratory indices connected with the administration of the investigating preparation. The decision about the advisability to continue the study and to pass to the 2nd part of volunteers and (or) to escalate the dose will be made by the "Independent committee for data monitoring (ICDM) for periodical examination of the clinical study, safety data and/or main parameters of the efficacy" as well it must be approved by the Local/Independent Ethical Committee of the Research centerе.

After getting the permission to continue the study the next group will be organized according to the analogous scheme: at first the first group of volunteers and then, after receiving the safety results in a written form, the 2nd group will be included, the decision to pass from the second group to the third will be the same.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Infectious Disease Clinical Hospital No. 1 of the Moscow Healthcare Department

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. Males and females within the age range from 18 to 40 years
2. Health physical condition must be confirmed by routine clinical, laboratory and instrumental methods of diagnosis (absence of gastrointestinal, renal, cardiovascular diseases, hepatic, blood disorders, cancer and infectious diseases)
3. Body-weight index within range from 18 to 30 kg\m2
4. Consent for using of reliable contraception (contraception sheath with spermicidal agents) while study and three months after the end of the study
5. Signed Participant Information Sheet and informed consent
6. Absence of specific antibodies (IgG, IgM, IgA) to Bordetella pertussis (negative ELISA results according to direction for ELISA test-system)
7. Absence of Bordetella pertussis DNA in nasopharyngeal swabs (negative PCR results)

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. Use of any medications (in particular herbal medications and dietary supplements) within 30 days after day 0 at the discretion of the investigator
8. Positive results of HIV, hepatitis B or C
9. Use of narcotic drugs and/or a history of drug/alcohol abuse
10. Allergic diseases in medical history (in particular drug reaction and food allergy)
11. 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
12. Current participation in any other clinical trial or participation (and during the whole study) in any clinical trial in the previous 3 months prior to day 0
13. Inability to adhere to the protocol
14. Acute infectious diseases within 4 weeks prior to screening
15. Wheezing on the results of peakflowmetry
16. Significant ECG changes
17. Pregnancy or lactation (for female volunteers)
18. Systolic blood pressure less than 90 mmHg or over than 130 mmHg; diastolic blood pressure less than 60 mmHg or over 90 mmHg
19. Heart rate less than 60 bpm or more than 90 bpm

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 Vaccine GamLPV; 9 individuals will be vaccinated intranasally with 2,5*10*8 bacteria cells (CFU)	Biological: Vaccine GamLPV; live intranasal vaccine for whooping cough prevention; Other Names: live intranasal Bordetella pertussis vaccine
Placebo Comparator: Group 1 placebo; 3 individuals will get placebo	Other: Placebo; Placebo
Experimental: Group 2 Vaccine GamLPV; 9 individuals will be vaccinated intranasally with 10*9 bacteria cells(CFU)	Biological: Vaccine GamLPV; live intranasal vaccine for whooping cough prevention; Other Names: live intranasal Bordetella pertussis vaccine
Placebo Comparator: Group 2 placebo; 3 individuals will get placebo	Other: Placebo; Placebo
Experimental: Group 3 Vaccine GamLPV; 9 individuals will be vaccinated intranasally with 4*10*9 bacteria cells(CFU)	Biological: Vaccine GamLPV; live intranasal vaccine for whooping cough prevention; Other Names: live intranasal Bordetella pertussis vaccine
Placebo Comparator: Group 3 placebo; 3 individuals will get placebo	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability	Evaluation of general safety and tolerability of medicinal product "GamLPV, a live intranasal vaccine for whooping cough prevention" in healthy human volunteers compared to placebo, detection the most frequent from possible adverse events of GamLPV	the total Time Frame is 150 days after the vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose ranging and optimal dose choice	Dose ranging and optimal dose choice for safety and tolerability of medicinal product GamLPV, a live intranasal vaccine for whooping cough prevention" in further clinical trials	the total Time Frame is 150 days after the vaccination
specific antibody response to B.pertussis	• To assess specific antibody response to B.pertussis after vaccination by "GamLPV, a live intranasal vaccine for whooping cough prevention"	the total Time Frame is 150 days after the vaccination
dynamics of bacteria generation in nasopharynx of human volunteers	To see if the attenuated B.pertussis bacteria have the ability to colonise the human respiratory tract after vaccination by "GamLPV, a live intranasal vaccine for whooping cough prevention" and to assess dynamics of bacteria generation in nasopharynx of human volunteers	the total Time Frame is 150 days after the vaccination
the B- and T-cell immune responses to B.pertussis	To assess the B- and T-cell immune responses to B.pertussis in response to vaccination by "GamLPV, a live intranasal vaccine for whooping cough prevention"	the total Time Frame is 150 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 13, 2017
• Primary Completion (Actual): December 19, 2017
• Study Completion (Actual): December 27, 2017

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: April 28, 2017
• First Posted (Actual): May 3, 2017

Study Record Updates

• Last Update Posted (Actual): December 28, 2017
• Last Update Submitted That Met QC Criteria: December 27, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: vaccine; Immunologic Factors; bordetella pertussis; whooping cough
• 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-01

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