Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR)
A Phase 1 Open-label, Dose Escalating Study of Artificial Shigella Flexneri 2a InvaplexAR Administered Intranasally to Healthy, Adult Volunteers to Evaluate Safety and Immunogenicity
3 other identifiers
interventional
38
1 country
1
Brief Summary
This study is an open-label, dose-escalating Phase 1 investigation of S. flexneri 2a InvaplexAR vaccine. A total of up to 40 subjects will receive one of four S. flexneri 2a InvaplexAR vaccine doses. The vaccine will be administered intranasally (without adjuvant).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2015
Shorter than P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2015
CompletedFirst Posted
Study publicly available on registry
May 15, 2015
CompletedStudy Start
First participant enrolled
October 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 13, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 13, 2016
CompletedResults Posted
Study results publicly available
July 22, 2020
CompletedFebruary 12, 2021
February 1, 2021
8 months
May 13, 2015
June 9, 2020
February 10, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Treatment Related Adverse Events
Number of adverse events related to the vaccine for each arm
166 days
Antibody Titers Against IgG and IgA Immunizing Antigens
Serum samples will be assayed for antibody titers against the immunizing antigens LPS, IpaB, IpaC, and S. flexneri 2a Invaplex at screening, and Days 0, 14, 28, 35, 42, and 56 for 36 subjects. Previously established high-titer specimens will be included on each plate to track day to day interassay variation. For each antigen, pre- and post-vaccination serum samples will be assayed side-by-side. The antibody titer assigned to each sample will represent the geometric mean of duplicate tests performed on 2 different days. Reciprocal endpoint titers \< 5 will be assigned a value of 2.5 for computational purposes. Seroconversion will be defined as a \> 4-fold increase in endpoint titer between pre-and post-vaccination samples AND a post-vaccination reciprocal titer \>10.
At screening and Days 0, 14, 28, 35, 42, and 56
Secondary Outcomes (2)
IgG and IgA Antigen-Specific Antibody Secreting Cell (ASC) Mucosal Responses
56 Days
IgG and IgA Antigen-Specific Antibody Lymphocyte Supernatant (ALS) Mucosal Responses
56 Days
Study Arms (4)
10 μg S. flexneri 2a Invaplex
ACTIVE COMPARATOR10 subjects vaccinated on days 0, 14, 28
50 μg S. flexneri 2a Invaplex
ACTIVE COMPARATOR10 subjects vaccinated on days 0, 14, 28
250 μg S. flexneri 2a Invaplex
ACTIVE COMPARATOR10 subjects vaccinated on days 0, 14, 28
500 μg S. flexneri 2a Invaplex
ACTIVE COMPARATOR10 subjects vaccinated on days 0, 14, 28
Interventions
The investigational product is S. flexneri 2a InvaplexAR. The product is composed of three individual components IpaB, IpaC, and LPS. The components were assembled into the high molecular weight S. flexneri 2a InvaplexAR complex and subsequently purified by ion-exchange chromatography yielding a bulk lot.
Eligibility Criteria
You may qualify if:
- Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
- Completion and review of comprehension test (achieved \> 70% accuracy).
- Signed informed consent document.
- Available for the required follow-up period and scheduled clinic visits.
- Women: Negative pregnancy test with understanding (through informed consent process) to not become pregnant nor to breastfeed during the study or within 3 months following last vaccination
You may not qualify if:
- Health problems (for example, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension, or any other conditions that might place the subjects at increased risk of adverse events)- study clinicians, in consultation with the PI, will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Research Monitor as appropriate.
- Clinically significant abnormalities on physical examination (chronic sinusitis or seasonal rhinitis) which compromise identification and interpretation of potential vaccine associated adverse effects.
- Use of immunosuppressive and/or immunomodulative drugs such as corticosteroids or chemotherapeutics that may influence antibody development.
- Immunosuppressive illnesses (including IgA deficiency defined by serum IgA below level of detection or \<7mg/dL).
- Participation in research involving another investigational product (defined as receipt of an investigational product or exposure to an invasive investigational device) 30 days before planned date of first vaccination or anytime throughout the duration of the study until the last study safety visit.
- Positive blood test for HBsAG, HCV, HIV-1/HIV-2.
- Clinically significant abnormalities on basic laboratory screening.
- Presence of significant unexplained laboratory abnormalities that in the opinion of the PI may potentially confound the analysis of the study results.
- Current smoker or smoker in past 1 year ('smoker' defined as daily cigarette, cigar, or pipe use for a period of at least 1 month).
- Research specific
- Structural abnormalities on sinus/nasal cavity examination.
- Rhinoplasty.
- Nasal polyps.
- Nasal ulcers.
- Deviated nasal septum. This question is being used to determine whether the volunteer has a clinically significant deviated septum that causes nasal obstruction (thereby causing difficulty breathing), interferes with normal sinus drainage, or obscures visualization of the posterior nasal cavity complicating examination and safety monitoring..
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Walter Reed Army Institute of Research, Clinical Trials Center
Silver Spring, Maryland, 20910, United States
Related Publications (1)
Duplessis C, Clarkson KA, Ross Turbyfill K, Alcala AN, Gutierrez R, Riddle MS, Lee T, Paolino K, Weerts HP, Lynen A, Oaks EV, Porter CK, Kaminski R. GMP manufacture of Shigella flexneri 2a Artificial Invaplex (InvaplexAR) and evaluation in a Phase 1 Open-label, dose escalating study administered intranasally to healthy, adult volunteers. Vaccine. 2023 Oct 6;41(42):6261-6271. doi: 10.1016/j.vaccine.2023.08.051. Epub 2023 Sep 2.
PMID: 37666695DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Christopher Duplessis, MD
- Organization
- Walter Reed Army Institute of Research (WRAIR) Clinical Trials Center (CTC)
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher Duplessis, MD, MPH, MS
Enteric Diseases Department Naval Medical Research Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2015
First Posted
May 15, 2015
Study Start
October 1, 2015
Primary Completion
May 13, 2016
Study Completion
May 13, 2016
Last Updated
February 12, 2021
Results First Posted
July 22, 2020
Record last verified: 2021-02