Evaluation of NDV-3A Vaccine in Preventing S. Aureus Colonization

Study Overview
=================
Brief Summary
-----------------
The proposed study aims to further evaluate the safety and immunogenicity of a candidate S. aureus vaccine NDV-3A, as well as its efficacy against acquisition of S. aureus

Detailed Description
-----------------
The investigators will conduct a Phase 2 clinical trial to evaluate the safety, immunogenicity, and efficacy of candidate vaccine NDV-3A (NovaDigm Therapeutics, Inc.) to prevent incident nasal acquisition of S. aureus among a population of military recruits at increased risk for S. aureus colonization and disease. Colonization is a risk factor for skin and soft tissue infection (SSTI), and the anterior nares is an important reservoir for S. aureus. Use of S. aureus nasal colonization (specifically, incident nasal colonization with S. aureus post-vaccination) as a primary endpoint will allow the investigators to pursue a statistically-valid and meaningful parameter related to S. aureus SSTI. The proposed trial may yield evidence to warrant evaluation of NDV-3A efficacy against SSTI in a large-scale, Phase 2/3 trial in this high risk population.

Official Title
-----------------
A Phase 2 Double-blind Placebo-controlled Study to Evaluate the Safety, Immunogenicity and Efficacy of NDV-3A Vaccine in Preventing S. Aureus Colonization

Conditions
-----------------
Staphylococcus Aureus

Intervention / Treatment
-----------------
* Biological: NDV-3A
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Active duty, male subject, 17-35 years of age, inclusive, at the time of screening. Assigned to one of the selected companies/battalions Informed of the nature of the study and has agreed to and is able to read, review, and sign the informed consent document prior to screening. Free of known significant health problems as established by the requirements to be enrolled in a military training program before entering into the study. Agrees to be reachable by phone, email or letter at 6 months post-vaccination. Exclusion Criteria: Reports receiving any investigational drug, investigational vaccine, or investigational device within 30 days prior to dosing; subjects will be allowed to receive routine vaccinations associated with training and any other prescribed medications not in the exclusion criteria. Presence of clinically significant SSTI (e.g., cellulitis, abscess) at screening or other skin or skin structure infections that would confound the interpretation of clinical response. Reports a history of allergic response(s), anaphylaxis, or other serious reactions to previous vaccinations. Reports a history of allergies to yeast Reports a history of anaphylaxis or other serious reactions to aluminum. Reports a history of autoimmune disease (psoriasis, etc.) Seropositive for HIV antibody. Reports the use of any immunosuppressive drugs, including systemic corticosteroids (more than 14 days at a dose of >20 mg/day prednisone or equivalent), within 4 weeks prior to dosing. Reports receiving any blood products within 3 months prior to dosing. Reports donating blood/plasma within 28 days prior to dosing. Illness causing temperature ≥ 100.4°F Evidence of abnormal, unresolved laboratory results in the subject's medical record for the following tests: hemoglobin, white blood cell count, platelet count, creatinine, and alanine aminotransferase Any other medical and/or social reason which, in the opinion of the investigator(s), would increase the subject's risk of having an adverse reaction as a result of participation in the study.

Ages Eligible for Study
-----------------
Minimum Age: 17 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blind, placebo-controlled, randomized study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NDV-3A<br>0.5 mL dose containing 300 micrograms of recombinant Als3 protein in phosphate-buffered saline and 0.5 mg aluminum as aluminum hydroxide | Biological: NDV-3A<br>* Single dose administered by intramuscular injection<br>|
| Placebo Comparator: Placebo<br>0.5 mL dose containing phosphate-buffered saline and 0.5 mg aluminum as aluminum hydroxide | Biological: Placebo<br>* Single dose administered by intramuscular injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevent acquisition of incident Staphylococcus aureus nasal colonization | Change in incident Staphylococcus aureus nasal colonization by study day 56 in a population of US Army trainees at Ft. Benning, GA | 56 days post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the efficacy of the NDV-3A vaccine | Describe SSTI rates within the training company as defined by the development of skin and soft tissue infection (SSTI) over the training period as compared to other companies in the battalion as well as historical data | 0-90 days | 
| Evaluation of the efficacy of the NDV-3A vaccine | Describe NDV-3A-associated delay in time to first nasal acquisition of S. aureus colonization | 0-90 days | 
| Evaluation of the efficacy of the NDV-3A vaccine | Describe reduction in cross-sectional prevalence of S. aureus nasal/oral colonization | 0-90 days | 
| Evaluation of safety and tolerability in all subjects | Occurrence of solicited adverse events (AE) over a 7-day follow-up period following vaccination | 0-7 days | 
| Evaluation of safety and tolerability in all subjects | Occurrence of unsolicited AEs over a 28-day follow-up period following vaccination | 0-28 days | 
| Evaluation of safety and tolerability in all subjects | Occurrence of serious adverse events (SAE) or Adverse Events of Special Interest (AESI) at any time during the study period (enrollment to final in-person follow-up visit) | 0-90 days | 
| Measurement and characterization of immunogenicity of NDV-3A | Describe the humoral immune response induced by NDV-3A using ELISA analysis of serum | 0-90 days | 
| Measurement and characterization of immunogenicity of NDV-3A | Describe the cell mediated immune responses induced by NDV-3A using ELISpot analysis of PBMCs | 0-14 days | 
| Describe the impact of NDV-3A on S. aureus acquisition and transmission | Following determination of taxonomy (via sequencing of 16S rRNA), determine the relative abundance and distribution of, and change in, bacterial species colonizing the nose and throat (i.e. nasal/oral microbiome) of military trainees during the training period. | 0-90 days | 
| Describe the impact of NDV-3A on S. aureus acquisition and transmission | Compare the compositions of the nasal/oral microbiome between study groups to assess the impact of NDV-3A vaccine on the nasal/oral microbiome. | 0-90 days | 
| Describe the impact of NDV-3A on S. aureus acquisition and transmission | Utilize a combination of epidemiologic, microbiologic, and genomic data on colonization isolates to describe the intra-class transmission dynamics of S. aureus among congregate military trainees | 0-90 days | 
| Describe the impact of NDV-3A on S. aureus acquisition and transmission | Conduct whole genome sequencing on isolates to describe the intra- and inter-host concordance of infecting and colonizing strains of S. aureus | 0-90 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Als3, SSTI, vaccine, NDV-3A, incident nasal colonization