CompletedNCT03455309Updated Jan 29, 2020

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

A Phase 2 interventional study of NDV-3A and Placebo in Staphylococcus Aureus, sponsored by NovaDigm Therapeutics, Inc.. Completed at 1 site in United States. Open to male participants aged 17 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-01-29.

Sponsored by NovaDigm Therapeutics, Inc. · Phase 2, Interventional, and Prevention

Phase: Phase 2
Study type: Interventional
Enrollment: 382
Allocation: Randomized
Ages: 17 Years to 35 Years
Sex: Male

Study 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

Read the 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.

Conditions studied

Staphylococcus Aureus

Keywords

Als3
SSTI
vaccine
NDV-3A
incident nasal colonization

Who can participate

Ages eligible: 17 Years to 35 Years
Sexes eligible: Male
Accepts healthy volunteers: Yes

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

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 design

Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 382 participants (actual)

Study arms

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
Placebo comparator
Placebo
0.5 mL dose containing phosphate-buffered saline and 0.5 mg aluminum as aluminum hydroxide
Biological: Placebo

Interventions

BiologicalNDV-3A
Single dose administered by intramuscular injection
BiologicalPlacebo
Single dose administered by intramuscular injection

What researchers measure

Primary outcomes

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
Time frame: 56 days post-vaccination

Secondary outcomes

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
Time frame: 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
Time frame: 0-90 days
Evaluation of the efficacy of the NDV-3A vaccine
Describe reduction in cross-sectional prevalence of S. aureus nasal/oral colonization
Time frame: 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
Time frame: 0-7 days
Evaluation of safety and tolerability in all subjects
Occurrence of unsolicited AEs over a 28-day follow-up period following vaccination
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 0-90 days

Study locations

1 site

Fort Benning
Fort Benning, Georgia 31905, United States

References and documents

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. PubMed 25489065 ↗
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. PubMed 23099329 ↗

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03455309
Lead sponsor: NovaDigm Therapeutics, Inc.
Collaborators: Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences
Responsible party: Sponsor
First posted: Mar 6, 2018
Start date: Jan 30, 2018
Primary completion: Jul 19, 2019
Completion: Oct 15, 2019
Last update: Jan 29, 2020

Study contacts

Jason W Bennett, MD

principal investigator · USU IDCRP

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jan 2020. You cannot join it, but the record below documents what was studied.

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