Recombinant Attenuated Salmonella Typhi Vaccine Vectors Producing Streptococcus Pneumoniae PspA

NCT01033409 | Completed Phase 1 DMC

• 1 other identifier: 09-RASV-Sp-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pneumonia

Keywords

Salmonella Typhi; pneumonia; oral; vaccine

Outcome Measures

Primary Outcomes (1)

• Safety (adverse events, including fever, grade 3 laboratory or systemic AEs, bacteremia, through 6 months), stool cultures and blood cultures

  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.

  6 months

Study Arms (4)

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.

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.

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.

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.

Biological: Salmonella Typhi-vectored pneumonia vaccine

Interventions

Salmonella Typhi-vectored pneumonia vaccine BIOLOGICAL

Liquid, oral dosage administered once at 10\^7 CFU in 10 mL phosphate-buffered saline

Also known as: RASV strains

S. Typhi-vectored pneumo vaccine 10^7

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Arizona State University: lead

Study Sites (1)

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104, United States

Location

MeSH Terms

Conditions

Pneumonia

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Sharon Frey, MD

  Saint Louis University Center for Vaccine Development, St. Louis, MO USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2009
• First Posted: December 16, 2009
• Study Start: August 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: November 2, 2011

Record last verified: 2011-11

Locations

US (1)