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

Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation

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.

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.

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.

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

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

• To assess specific antibody response to B.pertussis after vaccination by "GamLPV, a live intranasal vaccine for whooping cough prevention"

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

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"

Inclusion Criteria: Males and females within the age range from 18 to 40 years 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) Body-weight index within range from 18 to 30 kg\m2 Consent for using of reliable contraception (contraception sheath with spermicidal agents) while study and three months after the end of the study Signed Participant Information Sheet and informed consent Absence of specific antibodies (IgG, IgM, IgA) to Bordetella pertussis (negative ELISA results according to direction for ELISA test-system) Absence of Bordetella pertussis DNA in nasopharyngeal swabs (negative PCR results) 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 Use of any medications (in particular herbal medications and dietary supplements) within 30 days after day 0 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 or participation (and during the whole study) in any clinical trial in the previous 3 months prior to day 0 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