Single-ascending-dose Study of the Safety and Immunogenicity of NasoVAX

Study Overview
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Brief Summary
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This is a Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects will be screened within 28 days of randomization (Day 1).

Detailed Description
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This is a Phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of NasoVAX in healthy adults 18 to 49 years of age. Subjects will be screened within 28 days of randomization (Day 1). Approximately 60 subjects who meet all inclusion and no exclusion criteria and provide written informed consent will be enrolled into 3 sequential cohorts of 20 subjects each defined by the viral particle dose (1×10(9th), 1×10(10th), and 1×10(11th) vp). Within each cohort and its sentinel group, subjects will be randomized in a 3:1 ratio to receive 1 intranasal dose of NasoVAX or placebo (Day 1). A sentinel group of 5 subjects from each cohort will be dosed and followed through Day 8. Dosing of the remainder of each cohort may proceed if no events meeting stopping criteria have occurred. The SRC, consisting of the Investigator, the Medical Monitor, and a Sponsor Representative, will review AE, reactogenicity, and laboratory data through Day 8 for all subjects in each cohort before subjects are randomized to the next higher dose. If any event meeting stopping criteria occur, the SRC will review all available safety information before additional patients are dosed.

Official Title
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Single-ascending-dose Study of the Safety and Immunogenicity of NasoVAX

Conditions
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Influenza

Intervention / Treatment
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* Biological: NasoVAX


Participation Criteria
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Eligibility Criteria
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Subjects who meet all of the following criteria may be included in the study: Men and women 18 to 49 years of age, inclusive Good general health status as determined by the Investigator Adequate venous access for repeated phlebotomies Screening laboratory results within institutional normal range or Grade 1 elevation if the Investigator documents clinical insignificance. Creatine kinase or bilirubin may be Grade 2 if associated with normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the Investigator considers the result not to be clinically significant due to vigorous exercise or Gilbert's syndrome Negative drug and alcohol screen at Screening and predose on Day 1 For women who have not been surgically sterilized or have laboratory confirmation of postmenopausal status, negative pregnancy test Willingness to practice a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with a postmenopausal partner, monogamous relationship with vasectomized partner, vasectomy, surgical sterilization (hysterectomy, or bilateral tubal ligation, salpingectomy, or oophorectomy), licensed hormonal methods, intrauterine device (IUD), or consistent use of a barrier method (eg, condom, diaphragm) with spermicide for 28 days after the NasoVAX/placebo dose Willingness to participate and comply with all aspects of the study through the entire study period, including nasopharyngeal swabs and blood and urine samples Provision of written informed consent Subjects who meet any of the following criteria will be excluded from the study: Pregnant, possibly pregnant, or lactating women Household contacts of pregnant women, children < 5 years of age, or immunocompromised individuals for the period up through 2 weeks postvaccination Persons who care for pregnant women, children < 5 years of age, or immunocompromised individuals for the period up through 2 weeks postvaccination Body mass index > 35.0 kg/m2 Positive results for HIV, hepatitis B virus, or hepatitis C virus at Screening Asthma or other chronic lung disease that is greater than mild in severity. Specifically excluded are participants with the any of the following events in the past year: Daily symptoms Daily use of short acting beta 2 agonists Use of inhaled steroids or theophylline Use of pulse systemic steroids Emergency care or hospitalization related to asthma or other chronic lung disease Systemic steroids for asthma exacerbation History of diabetes mellitus (gestational diabetes is allowed if treatment was not required postpartum and serum glucose is currently in the normal range) History of coronary artery disease, arrhythmia, or congestive heart failure Clinically significant ECG abnormality as determined by the Investigator Poorly controlled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 95 mmHg) at Screening or predose on Day 1 History of anaphylaxis or angioedema Known allergy to any of the ingredients in the vaccine formulation History of chronic rhinitis, nasal septal defect, cleft palate, nasal polyps, or other nasal abnormality that might affect vaccine administration Previous nasal surgery or nasal cauterization Any symptoms of upper respiratory infection or temperature > 38°C within 3 days before Day 1 Any symptoms within 24 hours before Day 1 of upper respiratory illness of allergy flare-up that, in the opinion of the Investigator, presents as nasal congestion or rhinorrhea that could inhibit the proper administration of the IP Known or suspected malignancy, excluding non-melanoma skin cancers and other early stage surgically excised malignancies that the Investigator considers to be exceedingly unlikely to recur Immunocompromised individuals, including those who have used corticosteroids (including intranasal steroids), alkylating drugs, antimetabolites, radiation, immune-modulating biologics, or other immunomodulating therapies within 90 days before Day 1 or those who plan use during the study period Use of statin medication within 30 days before Day 1 (see list in Section 6.8.1) Receipt of intranasal medications (including over-the-counter medications) within 30 days before Day 1 Receipt of any investigational product (IP) within 30 days before Day 1 Receipt of any vaccine within 30 days before Day 1 Receipt of intranasal vaccine within 90 days before Day 1 Receipt of any influenza vaccine within 6 months before Day 1 Any change in medication for a chronic medical condition within 30 days before Day 1 Past regular use or current use of intranasal illicit drugs Smoking of any type (eg, cigarettes, electronic cigarettes, marijuana) or use of any tobacco product within 30 days before Day 1 Any medical, psychiatric, or social condition or occupational or other responsibility that in the judgment of the Investigator would interfere with or serve as a contraindication to protocol adherence, assessment of safety (including reactogenicity), or a subject's ability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Sequential Assignment
Interventional Model Description: Single ascending dose study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NasoVAX low dose<br>NasoVAX administered by intranasal spray at a single dose of 1×10(9th) viral particles (vp) versus placebo | Biological: NasoVAX<br>* Single ascending dose study<br>|
| Experimental: NasoVAX medium dose<br>NasoVAX administered by intranasal spray at a single dose of 1×10(10th) viral particles (vp) versus placebo | Biological: NasoVAX<br>* Single ascending dose study<br>|
| Experimental: NasoVAX high dose<br>NasoVAX administered by intranasal spray at a single dose of 1×10(11th) viral particles (vp) versus placebo | Biological: NasoVAX<br>* Single ascending dose study<br>|
| Placebo Comparator: Placebo<br>Normal saline administered by intranasal spray at a single dose | Biological: NasoVAX<br>* Single ascending dose study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-Emergent Adverse Events in Participants [Safety and Tolerability] | Adverse events (AEs): counts and percentages of subjects with AEs Day 1 to day 29 and Medically attended AEs (MAEs), serious AEs (SAEs), new-onset chronic illnesses (NCIs) from Day 1 to Day 181 | Day 1 to Day 181 | 
| Number of Treatment-Emergent Reactogenicity Events in Participants [Safety and Tolerability] | Reactogenicity: counts and percentages of subjects with 'yes' to any reactogenicity event (nasal irritation, sneezing, nasal congestion, sore throat, change in smell, change in taste, change in vision, eye pain, headache, fatigue, muscle ache, nausea, vomiting, diarrhea, chills, fever) | 14-days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HAI Immune Response | Antibody level measured by hemagglutination inhibition (HAI) in serum | Day 1 to Day 181 | 
| Microneutralization Immune Response | Antibody level measured by microneutralization in serum | Day 1 to Day 181 |