Safety Study of Live Attenuated Influenza Vaccine, CodaVax, Delivered Via Intranasal Spray

Study Overview
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Brief Summary
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This study is being conducted to assess the safety, tolerability, and immunogenicity of the live-attenuated CodaVax-H1N1 influenza vaccine as compared to normal saline placebo both administered via intranasal spray to healthy adults.

Official Title
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A Randomized Double-Blind, Placebo Controlled, Phase I Study of the Safety, Tolerability and Immunogenicity of a Live Attenuated H1N1 Vaccine in Healthy Individuals

Conditions
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Influenza

Intervention / Treatment
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* Biological: CodaVax-H1N1 influenza vaccine
* Biological: Normal Saline Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult volunteers, aged 18 to 45 years (at the time of screening) in good general health in the opinion of the Medical Investigator or delegate, with no significant medical history and no clinically significant abnormal findings at screening. Participants must use highly effective, double contraception from the Screening Visit and up to the Follow-up Visit (Day 30). Must be willing to comply with the following conditions to prevent the spread of Genetically modified organisms (GMO) according the Office of Gene Technology Regulator (OGTR) Licence (DIR 144): Hygiene measures intended to prevent interpersonal transmission of study drug must be implemented, including but not limited to frequent handwashing with soap or hand disinfectant, respiratory hygiene and cough etiquette within 7 days following vaccination Blood, tissue or organs must not be donated within 7 days of vaccination Severely immunosuppressed persons who require a protective environment are not to be cared for by the participant within 7 days of vaccination Contact is not to be made with severely immunosuppressed persons who require a protective environment within 7 days of vaccination All tissues and materials used to collect respiratory secretions are to be sealed in a primary container and placed within a secondary container so that it is not accessible to children or animals for 7 days until it is returned to the study site for disposal, for 7 days within vaccination Contact is not to be made with infants <6 months of age within 7 days of vaccination. Adequate venous access in the left or right arms to allow collection of a number of blood samples. Must be sero-susceptible ≤10 hemagglutination inhibition (HAI) titre to CA/07/2009 Influenza virus (pre-screen). Laboratory Testing: Full blood examination and biochemistry within the laboratory defined normal range unless deemed not clinically significant by the investigator, however a small drop below the normal range for Absolute Neutrophil Count (ANC) may be acceptable as per investigator discretion; Urinalysis: Negative urine glucose, negative or trace urine protein, negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic urinalysis within institutional range) Able to communicate effectively with study personnel and considered reliable, willing and cooperative in terms of compliance with the protocol requirements Participant does not intend to start or change an existing physical conditioning regimen prior to or during the study period Participant has voluntarily given written informed consent to participate in the study (prior study entry) Participant is available for the duration of the study Exclusion Criteria: Immunodeficiency (including HIV) or autoimmune disorder, or participant is currently taking drugs (excluding steroids, see exclusion criteria 16) or was undergoing a form of treatment within 3 months prior to study entry that affects the immune system, or participant is living with somebody with the same Participant is not to have had Guillain-Barre Syndrome Received blood or blood products in the 3 months prior to screening Received another vaccine within 30 days before screening Received another influenza vaccine from 2016 to present year Participants with plans to travel to the Northern Hemisphere during the Screening period Participated in another clinical study (involving any investigational product or device) within 60 days before screening Suffered previous anaphylactic reaction to foods, vaccines, drugs or hymenoptera stings, or has a history of severe allergic reactions (e.g. clinically severe urticaria, asthma) Participants with active asthma or a history of childhood asthma which was treated with corticosteroids. Participants with a known egg allergy If female, pregnant, planning to become pregnant, or lactating, or participants is living with somebody who is pregnant or lactating. Participant has a history of, or current evidence at the time of screening of abuse of alcohol or any drug substance, licit or illicit, or current alcohol consumption is > 4 standard drinks (or equivalent) per day History of any psychiatric illness or psychological disorder which may impair the ability to provide written informed consent or participate in the study Current or history of significant neurological, cardiovascular, pulmonary (including asthma), hepatic, rheumatic, autoimmune, hematological, metabolic or renal disorder Clinically significant abnormal laboratory value at screening as determined by the Investigator Known or suspected impairment/alteration of immune function, including: Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks /≥2 mg/kg body weight / day prednisone ≥2 weeks) within 60 days prior to Day 0 (use of inhaled, IN, or topical corticosteroids is allowed, unless used for the management of asthma - see exclusion criteria 9). Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks /≥2 mg/kg body weight/day prednisone ≥ 2 weeks) within 60 days prior to Day 0. Or participant is living with somebody with the same Unusual dietary habits and excessive or unusual vitamin intake likely, in the opinion of the Investigator, to affect safety parameters Participant is sero-positive to hepatitis C virus or hepatitis B virus. Body temperature (oral) ≥38.0ºC or acute illness within 5 days prior to vaccination Any other significant finding that, in the opinion of the Investigator, would increase the risk of the individual having an adverse outcome from participating in this study Participant is a member of the team or is related or in a dependent relationship with a member of the study team, as defined as the Sponsor or study site personnel

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normal Saline Placebo<br>Saline (0.9%) | Biological: Normal Saline Placebo<br>* Saline (0.9%) administered intranasally via sprayer<br>|
| Experimental: CodaVax-H1N1<br>Live-attenuated influenza vaccine | Biological: CodaVax-H1N1 influenza vaccine<br>* CodaVax-H1N1, a live attenuated vaccine (LAIV) strain based on the A/California/07/2009 (H1N1) influenza virus, administered once intranasally via a sprayer at a dose of 8 x10^5 plaque forming units (PFU).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactions to vaccine | Number of solicited local and systemic reactions for CodaVax-H1N1 and placebo | 6 days | 
| Adverse events (AEs) | Number of subjects with AEs for CodaVax-H1N1 and placebo | 30 days | 
| Serious adverse events (SAEs) | Number of subjects with SAEs for CodaVax-H1N1 and placebo | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAI antibody titers against A/California/07/2009 | Geometric mean titers (GMT) of anti-A/California/07/2009 (H1N1) antibodies (Hemagglutination inhibition, HAI) for each treatment arm | Day 0 and 30 | 
| Increase in HAI titer against A/California/07/2009 | Geometric mean fold increase (GMFI) of anti-A/California/07/2009 (H1N1) HAI serum antibodies for each treatment arm | Day 0 and 30 | 
| HAI sero-response | The proportion of participants, regardless of sero-status, within each treatment arm who experience an H1N1 CA/07/2009 specific sero-response post-dose. Sero-response is defined as a ≥4-fold rise in HAI titer from baseline. | Day 0 and 30 | 
| Serum IgG response | The proportion of participants within each treatment arm with a greater or equal to 2-fold rise in serum lgG antibody responses to whole virus CA/07/2009 by ELISA | Day 0 and 30 | 
| Increase in serum IgG | Geometric mean fold increase (GMFI) within each treatment arm in serum lgG antibody responses to whole virus CA/07/2009 by ELISA | Day 0 and 30 | 
| Serum IgA response | The proportion of participants within each treatment arm with a greater or equal to 2-fold rise in serum lgA antibody responses to whole virus CA/07/2009 by ELISA | Day 0 and 30 | 
| Increase in serum IgA | Geometric mean fold increase (GMFI) within each treatment arm in serum lgA antibody responses to whole virus CA/07/2009 by ELISA | Day 0 and 30 | 
| Salivary IgA Response | The proportion of participants within each treatment arm with a greater or equal to 2-fold rise in salivary lgA antibody responses to whole virus CA/07/2009 by ELISA | Day 0 and 30 | 
| Increase in salivary IgA | Geometric mean fold increase (GMFI) within each treatment arm in salivary lgA antibody responses to whole virus CA/07/2009 by ELISA | Day 0 and 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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live-attenuated vaccine, influenza vaccine