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

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

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

Study Overview

• Status: Completed
• Conditions: Staphylococcus Aureus
• Intervention / Treatment: Biological: NDV-3A; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 382
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Fort Benning, Georgia, United States, 31905
      • Fort Benning

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NDV-3A; 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; Single dose administered by intramuscular injection
Placebo Comparator: Placebo; 0.5 mL dose containing phosphate-buffered saline and 0.5 mg aluminum as aluminum hydroxide	Biological: Placebo; Single dose administered by intramuscular injection

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

Collaborators and Investigators

• Sponsor: NovaDigm Therapeutics, Inc.
• Collaborators: Uniformed Services University of the Health Sciences; Infectious Diseases Clinical Research Program
• Investigators: Principal Investigator: Jason W Bennett, MD, USU IDCRP

Publications and helpful links

General Publications

• Yeaman MR, Filler SG, Chaili S, Barr K, Wang H, Kupferwasser D, Hennessey JP Jr, Fu Y, Schmidt CS, Edwards JE Jr, Xiong YQ, Ibrahim AS. Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection. Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5555-63. doi: 10.1073/pnas.1415610111. Epub 2014 Dec 8.
• Schmidt CS, White CJ, Ibrahim AS, Filler SG, Fu Y, Yeaman MR, Edwards JE Jr, Hennessey JP Jr. NDV-3, a recombinant alum-adjuvanted vaccine for Candida and Staphylococcus aureus, is safe and immunogenic in healthy adults. Vaccine. 2012 Dec 14;30(52):7594-600. doi: 10.1016/j.vaccine.2012.10.038. Epub 2012 Oct 22.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2018
• Primary Completion (Actual): July 19, 2019
• Study Completion (Actual): October 15, 2019

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (Actual): March 6, 2018

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: vaccine; Als3; SSTI; NDV-3A; incident nasal colonization
• Other Study ID Numbers: NDV3A-006; IDCRP-104 (Other Identifier: IDCRP, USU)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No