PneumoniaPhase 1NCT01033409
Recombinant Attenuated Salmonella Typhi Vaccine Vectors Producing Streptococcus Pneumoniae PspA
A Phase 1 study testing Salmonella Typhi-vectored pneumonia vaccine in people with Pneumonia, run by Arizona State University at 1 site in United States.
Trial summary
In this Phase I clinical study, three recombinant, avirulent Salmonella Typhi (RASV) strains each expressing the Streptococcus pneumoniae surface protein, PspA, will be compared as live biological vaccine vectors to evaluate safe and tolerable, single, oral dose levels in adult subjects. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Pneumonia
- What is being tested?
- Salmonella Typhi-vectored pneumonia vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Jul 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects will be healthy adults who fully understand the purpose and details of the study.
- Age: 18-40 years inclusive at the time of enrollment
- Sex: Male or non-pregnant female Note: For females, negative pregnancy test at the time of entry. Females agree to use effective birth control measures to prevent pregnancy for one month prior to vaccination and for 28 days after vaccination and while on antibiotics.
- Willing and able to remain in the inpatient facility for the duration of approximately 13-15 days and longer if needed.
- In good health
- Willing and able to provide past medical history
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- History of normal,regular bowel habits defined by at least 3 stools per week and less than three stools per day without frequent (greater than one per month) use of laxatives or antidiarrheal agents
- Normal physical examination
- Laboratory evaluation:
- Urine dipstick: negative or trace protein Negative urine glucose Complete blood count: WBC, hemoglobin and neutrophil count within normal limits SGPT (ALT) and alkaline phosphatase within normal limits Blood urea nitrogen (BUN), creatinine within normal limits Nonreactive ELISA for HIV-1 Negative HCV-Ab Negative HBSAg Negative nasopharyngeal (a nose and throat swab) culture for S. pneumoniae
- Normal gallbladder ultrasound (ie, no gall stones)
- Able to understand and follow enteric precautions, i.e., practice good hygiene, wash hands thoroughly after using the toilet and avoid food preparation for others until shedding has resolved.
- Lives and works in situations with access to restrooms or bathrooms with flush toilets.
- Willing to avoid eating undercooked poultry and eggs.
- Able to read and willing to sign informed consent form.
- Willing and able to complete a questionnaire to demonstrate an understanding of various protocol issues including potential adverse effects and precautions to limit the spread of Salmonella as discussed in the informed consent.
- Willing and able to undergo rectal swabbing or stool collection.
- Willing and able to maintain a daily memory aid of potential vaccine-associated adverse events, record oral temperatures and collect stool specimens
- Agrees to not be involved in another study during this trial unless discussed with the investigator and approved.
Who cannot join
- History of Salmonella infection or vaccination
- History of pneumococcal vaccine
- Employed as a health care worker with any patient contact, child care provider, long-term care, assisted living or nursing home care taker, or food handler. Has close contact with children less than one year of age, and has close or intimate contact with immunocompromised persons.
- Pregnant or lactating women
- Placement of any prosthetic device of any kind, including but not limited to, orthopedic implants, CNS shunts, endovascular grafts or shunts, cardiac pacemakers, and cochlear implants
- History of splenectomy
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- History of gall bladder disease
- History of gastric achlorhydria or use of B12
- Frequent antacid or H2 blocker usage (i.e., Tagamet) (more than once a week)
- History of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications. [Persons with vitiligo or thyroid disease (e.g. taking thyroid hormone replacement) are not excluded.]
- History of medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol
- History of diarrheal illness within 30 days prior to enrollment (Diarrhea is defined as loose, watery stools occurring more than three times a day lasting more than a day and/or associated with fever.)
- History of anaphylaxis or other serious adverse reactions to vaccines
- History of allergy to ciprofloxacin and quinolones, ampicillin, penicillin, amoxicillin and third generation cephalosporins.
- History of any antibiotic therapy within 14 days prior to vaccination
- Receipt of live attenuated vaccine within 30 days prior to the study
- Receipt of any vaccine within 14 days prior to the study
- Use of experimental agents within 30 days prior to the study
- Receipt of blood products or immune globulin within 6 months prior to the study
- Donation of a unit of blood within 56 days prior to vaccination and for the duration of the study
- Persons taking inhaled steroids will be excluded.
- Persons who required pulsed steroids for conditions other than poison ivy will be excluded.
- Persons who required pulsed steroids for poison ivy within 14 days prior to vaccination will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Saint Louis University Center for Vaccine Development
St Louis, Missouri, 63104
About this study
Official title: Comparative Phase I Safety and Immunogenicity in Adult Volunteers of Three Recombinant Attenuated Salmonella Typhi Vaccine Vectors Producing Streptococcus Pneumoniae Surface Protein Antigen PspA
In this Phase I clinical study, three recombinant, avirulent Salmonella Typhi (RASV) strains each expressing the Streptococcus pneumoniae surface protein, PspA, will be compared as live biological vaccine vectors to evaluate safe and tolerable, single, oral dose levels in adult subjects.
Read the detailed description
The use of attenuated Salmonella strains that are unable to cause clinical disease but trigger a self-limiting infection leading to stimulation of protective immunity presents an attractive alternative to killed and subunit vaccines. Live, attenuated Salmonella strains have been shown to be excellent carriers, or vectors, for prokaryotic or eukaryotic antigens, being able to stimulate strong systemic and local immune responses against the expressed antigens. Three Salmonella Typhi strains have been engineered to express a gene encoding the alpha-helical domain of the Streptococcus pneumoniae surface protein, PspA, and will serve as live biological vaccine vectors in the proposed clinical trial to evaluate maximum safe and tolerable single dose levels after their oral administration to subjects. In this Phase I study, healthy young adults 18-40 years of age will participate in a dose escalating, dose sequential study divided into four Arms to receive doses of 10^7, 10^8, 10^9 and 10^10 CFU. Each Arm (1-4) will consist of 3 groups of 5 subjects per group to receive a single oral dose of one of three recombinant attenuated S. Typhi vaccine vectors producing the pneumococcal antigen PspA. Each group per Arm will receive the same dose of one of the three vaccines for a total of 60 subjects (15 subjects per dose-escalating Arm, 3 groups per Arm, 5 subjects per group). Subject participation lasts 6 months after receiving the oral vaccine dosage with approximately the first 12-15 days (study Days 0-14) in confinement. Release criteria include 2 negative blood cultures in a row through study Day 7 (inpatient monitoring for 8 days) and 2 negative stool cultures in a row through study Day 5. The objectives of the study are 1) to evaluate maximum safe tolerable single dose levels of the three recombinant attenuated S. Typhi vaccine vectors using dose-escalation, dose-sequential studies in healthy adult subjects, and 2) to evaluate immunogenicity of the three recombinant attenuated S. Typhi vaccine vectors with regard to their abilities to induce mucosal and systemic antibody responses to the S. pneumoniae PspA and S. Typhi antigens. The vaccines are not anticipated to prevent disease. Although the immune responses generated by the vaccine vectors may confer some degree of protection against future infection with S. pneumoniae and S. Typhi, such protection is incidental. It is not the goal of this study to develop or test either a pneumonia or typhoid vaccine, but to select the S. Typhi vector that provides optimal delivery of the PspA antigen in a safe and immunogenic manner.
- Conditions
- Pneumonia
- Being tested
- Salmonella Typhi-vectored pneumonia vaccine
- Keywords
- Salmonella Typhi, pneumonia, oral, vaccine
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Salmonella Typhi-vectored pneumonia vaccineBiological
Also called RASV strains
Liquid, oral dosage administered once at 10^7 CFU in 10 mL phosphate-buffered saline
Salmonella Typhi-vectored pneumonia vaccineBiological
Also called RASV strains
Liquid, oral dosage administered once at 10^8 CFU in 10 mL phosphate-buffered saline
Salmonella Typhi-vectored pneumonia vaccineBiological
Also called RASV strains
Liquid, oral dosage administered once at 10^9 CFU in 10 mL phosphate-buffered saline
Salmonella Typhi-vectored pneumonia vaccineBiological
Also called RASV strains
Liquid, oral dosage administered once at 10^10 CFU in 10 mL phosphate-buffered saline
| Study group | Role | What they receive |
|---|---|---|
| S. Typhi-vectored pneumo vaccine 10^7 | Experimental | Arm 1 will evaluate three attenuated S. Typhi strains administered to 3 groups of 5 subjects in single oral doses (10^7 CFU) for safety and immunogenicity. Dose escalation for each strain will proceed after demonstrating the safety and tolerability of 10^7 CFU oral dosage through Day 28. Receives: Biological: Salmonella Typhi-vectored pneumonia vaccine |
| S. Typhi-vectored pneumo vaccine 10^8 | Experimental | Arm 2 will evaluate three attenuated S. Typhi strains administered to 3 groups of 5 subjects in single oral doses (10^8 CFU) for safety and immunogenicity. Dose escalation for each strain will proceed after demonstrating the safety and tolerability of 10^8 CFU oral dosage through Day 28. Receives: Biological: Salmonella Typhi-vectored pneumonia vaccine |
| S. Typhi-vectored pneumo vaccine 10^9 | Experimental | Arm 3 will evaluate three attenuated S. Typhi strains administered to 3 groups of 5 subjects in single oral doses (10^9 CFU) for safety and immunogenicity. Dose escalation for each strain will proceed after demonstrating the safety and tolerability of 10^9 CFU oral dosage through Day 28. Receives: Biological: Salmonella Typhi-vectored pneumonia vaccine |
| S. Typhi-vectored pneumo vaccine 10^10 | Experimental | Arm 4 will evaluate three attenuated S. Typhi strains administered to 3 groups of 5 subjects in single oral doses (10^10 CFU) for safety and immunogenicity. Dose escalation for each strain will proceed after demonstrating the safety and tolerability of 10^10 CFU oral dosage through Day 28. Receives: Biological: Salmonella Typhi-vectored pneumonia vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (adverse events, including fever, grade 3 laboratory or systemic AEs, bacteremia, through 6 months), stool cultures and blood cultures
Measured: 6 months
Secondary outcomes (1)
Immunogenicity as measured by ELISA (IgA and IgG, PspA , S. Typhi LPS and OMPs) for days 0, 7, 28, 84 and 160 and ELISPOT (IgA PspA , S. Typhi LPS and OMPs) on Days 0 and 7.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2009 (estimated)
- Study startAug 2009
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- More trials run by Arizona State UniversityThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arizona State University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sharon Frey, MD, Principal investigator, Saint Louis University Center for Vaccine Development, St. Louis, MO USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01033409
- Sponsor's protocol ID
- 09-RASV-Sp-01
- Status last verified
- Nov 2011
- First submitted
- 16 Nov 2009
- Last updated
- 2 Nov 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Phase I Safety and Immunogenicity in Adult Volunteers of Three Recombinant Attenuated Salmonella Typhi Vaccine Vectors Producing Streptococcus Pneumoniae Surface Protein Antigen PspA
- ClinicalTrials.gov ID
- NCT01033409
- Acronym / sponsor ID
- 09-RASV-Sp-01
- Conditions
- Pneumonia
- Keywords
- Salmonella Typhi, pneumonia, oral, vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Arizona State UniversityUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 16 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this Phase I clinical study, three recombinant, avirulent Salmonella Typhi (RASV) strains each expressing the Streptococcus pneumoniae surface protein, PspA, will be compared as live biological vaccine vectors to evaluate safe and tolerable, single, oral dose levels in adult subjects.
Detailed description
The use of attenuated Salmonella strains that are unable to cause clinical disease but trigger a self-limiting infection leading to stimulation of protective immunity presents an attractive alternative to killed and subunit vaccines. Live, attenuated Salmonella strains have been shown to be excellent carriers, or vectors, for prokaryotic or eukaryotic antigens, being able to stimulate strong systemic and local immune responses against the expressed antigens. Three Salmonella Typhi strains have been engineered to express a gene encoding the alpha-helical domain of the Streptococcus pneumoniae surface protein, PspA, and will serve as live biological vaccine vectors in the proposed clinical trial to evaluate maximum safe and tolerable single dose levels after their oral administration to subjects. In this Phase I study, healthy young adults 18-40 years of age will participate in a dose escalating, dose sequential study divided into four Arms to receive doses of 10^7, 10^8, 10^9 and 10^10 CFU. Each Arm (1-4) will consist of 3 groups of 5 subjects per group to receive a single oral dose of one of three recombinant attenuated S. Typhi vaccine vectors producing the pneumococcal antigen PspA. Each group per Arm will receive the same dose of one of the three vaccines for a total of 60 subjects (15 subjects per dose-escalating Arm, 3 groups per Arm, 5 subjects per group). Subject participation lasts 6 months after receiving the oral vaccine dosage with approximately the first 12-15 days (study Days 0-14) in confinement. Release criteria include 2 negative blood cultures in a row through study Day 7 (inpatient monitoring for 8 days) and 2 negative stool cultures in a row through study Day 5. The objectives of the study are 1) to evaluate maximum safe tolerable single dose levels of the three recombinant attenuated S. Typhi vaccine vectors using dose-escalation, dose-sequential studies in healthy adult subjects, and 2) to evaluate immunogenicity of the three recombinant attenuated S. Typhi vaccine vectors with regard to their abilities to induce mucosal and systemic antibody responses to the S. pneumoniae PspA and S. Typhi antigens. The vaccines are not anticipated to prevent disease. Although the immune responses generated by the vaccine vectors may confer some degree of protection against future infection with S. pneumoniae and S. Typhi, such protection is incidental. It is not the goal of this study to develop or test either a pneumonia or typhoid vaccine, but to select the S. Typhi vector that provides optimal delivery of the PspA antigen in a safe and immunogenic manner.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| S. Typhi-vectored pneumo vaccine 10^7 | Experimental | Biological: Salmonella Typhi-vectored pneumonia vaccineArm 1 will evaluate three attenuated S. Typhi strains administered to 3 groups of 5 subjects in single oral doses (10^7 CFU) for safety and immunogenicity. Dose escalation for each strain will proceed after demonstrating the safety and tolerability of 10^7 CFU oral dosage through Day 28. |
| S. Typhi-vectored pneumo vaccine 10^8 | Experimental | Biological: Salmonella Typhi-vectored pneumonia vaccineArm 2 will evaluate three attenuated S. Typhi strains administered to 3 groups of 5 subjects in single oral doses (10^8 CFU) for safety and immunogenicity. Dose escalation for each strain will proceed after demonstrating the safety and tolerability of 10^8 CFU oral dosage through Day 28. |
| S. Typhi-vectored pneumo vaccine 10^9 | Experimental | Biological: Salmonella Typhi-vectored pneumonia vaccineArm 3 will evaluate three attenuated S. Typhi strains administered to 3 groups of 5 subjects in single oral doses (10^9 CFU) for safety and immunogenicity. Dose escalation for each strain will proceed after demonstrating the safety and tolerability of 10^9 CFU oral dosage through Day 28. |
| S. Typhi-vectored pneumo vaccine 10^10 | Experimental | Biological: Salmonella Typhi-vectored pneumonia vaccineArm 4 will evaluate three attenuated S. Typhi strains administered to 3 groups of 5 subjects in single oral doses (10^10 CFU) for safety and immunogenicity. Dose escalation for each strain will proceed after demonstrating the safety and tolerability of 10^10 CFU oral dosage through Day 28. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Subjects will be healthy adults who fully understand the purpose and details of the study.
- Age: 18-40 years inclusive at the time of enrollment
- Sex: Male or non-pregnant female Note: For females, negative pregnancy test at the time of entry. Females agree to use effective birth control measures to prevent pregnancy for one month prior to vaccination and for 28 days after vaccination and while on antibiotics.
- Willing and able to remain in the inpatient facility for the duration of approximately 13-15 days and longer if needed.
- In good health
Key exclusion criteria (23 listed)
- History of Salmonella infection or vaccination
- History of pneumococcal vaccine
- Employed as a health care worker with any patient contact, child care provider, long-term care, assisted living or nursing home care taker, or food handler. Has close contact with children less than one year of age, and has close or intimate contact with immunocompromised persons.
- Pregnant or lactating women
- Placement of any prosthetic device of any kind, including but not limited to, orthopedic implants, CNS shunts, endovascular grafts or shunts, cardiac pacemakers, and cochlear implants
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 |
|---|---|---|
| Salmonella Typhi-vectored pneumonia vaccineAlso: RASV strainsLiquid, oral dosage administered once at 10^7 CFU in 10 mL phosphate-buffered saline | Biological | S. Typhi-vectored pneumo vaccine 10^7 |
| Salmonella Typhi-vectored pneumonia vaccineAlso: RASV strainsLiquid, oral dosage administered once at 10^8 CFU in 10 mL phosphate-buffered saline | Biological | S. Typhi-vectored pneumo vaccine 10^8 |
| Salmonella Typhi-vectored pneumonia vaccineAlso: RASV strainsLiquid, oral dosage administered once at 10^9 CFU in 10 mL phosphate-buffered saline | Biological | S. Typhi-vectored pneumo vaccine 10^9 |
| Salmonella Typhi-vectored pneumonia vaccineAlso: RASV strainsLiquid, oral dosage administered once at 10^10 CFU in 10 mL phosphate-buffered saline | Biological | S. Typhi-vectored pneumo vaccine 10^10 |
Primary outcome
Safety (adverse events, including fever, grade 3 laboratory or systemic AEs, bacteremia, through 6 months), stool cultures and blood cultures
Time frame: 6 months
1 secondary outcome
Immunogenicity as measured by ELISA (IgA and IgG, PspA , S. Typhi LPS and OMPs) for days 0, 7, 28, 84 and 160 and ELISPOT (IgA PspA , S. Typhi LPS and OMPs) on Days 0 and 7.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2011.
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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.
Sharon Frey, MD principal investigator
Saint Louis University Center for Vaccine Development, St. Louis, MO USA
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 Salmonella Typhi-vectored pneumonia vaccine in people with Pneumonia, run by Arizona State University 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 19 inclusion and 23 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 2 Nov 2011. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety (adverse events, including fever, grade 3 laboratory or systemic AEs, bacteremia, through 6 months), stool cultures and blood cultures (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Nov 2011.