ShigellosisPhase 1NCT02445963
Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR)
A Phase 1 study testing Shigella flexneri 2a InvaplexAR in people with Shigellosis and Bacillary Dysentery, run by U.S. Army Medical Research and Development Command at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Shigellosis, Bacillary Dysentery
- What is being tested?
- Shigella flexneri 2a InvaplexAR
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2015to 13 May 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 30Show fewer
- 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..
- Chronic sinusitis/rhinitis.
- Current or planned use of nasal topical corticosteroids and/or nasal spray medications in the 4 weeks prior to dosing or during the study vaccination period.
- Current or recent history (in the past 5 years) of reactive airway disease (asthma), chronic obstructive pulmonary disease, or chronic bronchitis.
- History of Bell's palsy.
- Chronic use (weekly or more often) of anti-diarrheal, anti-constipation, or antacid therapy (excluding use associated with spicy meals).
- Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis.
- Personal or family history of inflammatory arthritis.
- Positive blood test for HLA-B27.
- History of allergy to any vaccine.
- Prior Exposure to Shigella
- Serum IgG titer ≥ 2500 to Shigella flexneri 2a LPS.
- History of microbiologically confirmed Shigella infection in the past 3 years.
- Received previous experimental Shigella vaccine or live Shigella challenge.
- Travel to countries with symptoms of travelers' diarrhea where Shigella or other enteric infections are endemic (most of the developing world) within the past 6 months prior to dosing.
- Occupation involving handling of Shigella bacteria currently, or in the past 3 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
Walter Reed Army Institute of Research, Clinical Trials Center
Silver Spring, Maryland, 20910
About this study
Official title: 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
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).
Read the detailed description
The vaccine will be administered on Days 0,14, and 28. Volunteers (10 per group [8 minimum]) will receive the same dose at each vaccination dependent upon group assignment. Groups will be divided according to the table below. An interval no less than 1 week will separate the third dose of a group from the first dose of the next group (receiving an increased InvaplexAR dose). Blood, stool, and saliva specimens will be collected at pre-specified intervals to examine systemic and mucosal vaccine antigen-specific immune responses. Ocular tear samples will be collected in groups C and D. Vaccine safety will be actively monitored during vaccination and for 28 days following the third vaccine dose. The decision to advance to the next dose level is based on the safety assessment (not immunogenicity). A dose level with no occurrence of stopping criteria in the 7 days following the last vaccine dose will prompt moving to the next higher level. All safety data will be summarized and reviewed with the research monitor prior to dose escalation. In addition, a report of all safety data will be provided to the sponsor's safety office for informational purposes.
- Conditions
- Shigellosis, Bacillary Dysentery
- Being tested
- Shigella flexneri 2a InvaplexAR
- Medical subject headings
- Dysentery, Bacillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Shigella flexneri 2a InvaplexARBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 10 μg S. flexneri 2a Invaplex | Active comparator | 10 subjects vaccinated on days 0, 14, 28 Receives: Biological: Shigella flexneri 2a InvaplexAR |
| 50 μg S. flexneri 2a Invaplex | Active comparator | 10 subjects vaccinated on days 0, 14, 28 Receives: Biological: Shigella flexneri 2a InvaplexAR |
| 250 μg S. flexneri 2a Invaplex | Active comparator | 10 subjects vaccinated on days 0, 14, 28 Receives: Biological: Shigella flexneri 2a InvaplexAR |
| 500 μg S. flexneri 2a Invaplex | Active comparator | 10 subjects vaccinated on days 0, 14, 28 Receives: Biological: Shigella flexneri 2a InvaplexAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Treatment Related Adverse Events
Number of adverse events related to the vaccine for each arm
Measured: 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.
Measured: 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
ASC responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ASC responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ASC response was defined as > 10 ASCs above baseline.
Measured: 56 Days
IgG and IgA Antigen-Specific Antibody Lymphocyte Supernatant (ALS) Mucosal Responses
ALS responses were assessed using isolated peripheral blood mononuclear cells (PBMCs). For each antigen, pre- and post-vaccination samples were tested on the same plates for total and vaccine-specific numbers. The ALS responses indirectly reflect intestinal immune responses through measurement of antigen-specific B-lymphocytes in systemic circulation before homing to gut effector sites. An ALS response was defined as a ≥ 4-fold increase over baseline ALS titers.
Measured: 56 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2015 (estimated)
- Study start1 Oct 2015
- Primary completion13 May 2016
- Study completion13 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ShigellosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Christopher Duplessis, MD, MPH, MS, Principal investigator, Enteric Diseases Department Naval Medical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02445963
- Sponsor's protocol ID
- S-15-19
- Other IDs
- A-18716, NMRC.2015.0003
- Status last verified
- Feb 2021
- First submitted
- 13 May 2015
- Last updated
- 12 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 37666695
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02445963
- Acronym / sponsor ID
- S-15-19
- Conditions
- Shigellosis, Bacillary Dysentery
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Study start
- 1 Oct 2015 (actual)
- Primary completion
- 13 May 2016 (actual)
- Study completion
- 13 May 2016 (actual)
- First posted
- 15 May 2015 (estimated)
- Results
- Posted 22 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The vaccine will be administered on Days 0,14, and 28. Volunteers (10 per group [8 minimum]) will receive the same dose at each vaccination dependent upon group assignment. Groups will be divided according to the table below. An interval no less than 1 week will separate the third dose of a group from the first dose of the next group (receiving an increased InvaplexAR dose). Blood, stool, and saliva specimens will be collected at pre-specified intervals to examine systemic and mucosal vaccine antigen-specific immune responses. Ocular tear samples will be collected in groups C and D. Vaccine safety will be actively monitored during vaccination and for 28 days following the third vaccine dose. The decision to advance to the next dose level is based on the safety assessment (not immunogenicity). A dose level with no occurrence of stopping criteria in the 7 days following the last vaccine dose will prompt moving to the next higher level. All safety data will be summarized and reviewed with the research monitor prior to dose escalation. In addition, a report of all safety data will be provided to the sponsor's safety office for informational purposes.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 10 μg S. flexneri 2a Invaplex | Active comparator | Biological: Shigella flexneri 2a InvaplexAR10 subjects vaccinated on days 0, 14, 28 |
| 50 μg S. flexneri 2a Invaplex | Active comparator | Biological: Shigella flexneri 2a InvaplexAR10 subjects vaccinated on days 0, 14, 28 |
| 250 μg S. flexneri 2a Invaplex | Active comparator | Biological: Shigella flexneri 2a InvaplexAR10 subjects vaccinated on days 0, 14, 28 |
| 500 μg S. flexneri 2a Invaplex | Active comparator | Biological: Shigella flexneri 2a InvaplexAR10 subjects vaccinated on days 0, 14, 28 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Shigella flexneri 2a InvaplexARThe 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. | Biological | 10 μg S. flexneri 2a Invaplex, 250 μg S. flexneri 2a Invaplex, 50 μg S. flexneri 2a Invaplex, 500 μg S. flexneri 2a Invaplex |
Primary outcome
Number of Treatment Related Adverse Events
Time frame: 166 days
Number of adverse events related to the vaccine for each arm
Antibody Titers Against IgG and IgA Immunizing Antigens
Time frame: At screening and Days 0, 14, 28, 35, 42, and 56
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.
2 secondary outcomes
IgG and IgA Antigen-Specific Antibody Secreting Cell (ASC) Mucosal Responses
Time frame: 56 Days
IgG and IgA Antigen-Specific Antibody Lymphocyte Supernatant (ALS) Mucosal Responses
Time frame: 56 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37666695Duplessis 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Duplessis, MD, MPH, MS principal investigator
Enteric Diseases Department Naval Medical Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Shigella flexneri 2a InvaplexAR in people with Shigellosis and Bacillary Dysentery, run by U.S. Army Medical Research and Development Command at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Treatment Related Adverse Events (time frame: 166 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02445963, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2021.