Safety and Immunogenicity of CVD 1902 Oral Attenuated Vaccine to Prevent S. Paratyphi A Infection

NCT01129453 | Completed Phase 1 DMC

• 4 other identifiers: HP-00045057Paratyphi CVD 1000DMID 09-0020U54AI057168
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine whether CVD 1902 (a live, attenuated, oral vaccine) is safe and effective in the prevention of Salmonella enterica serovar paratyphi A infection.

Conditions

Salmonella

Keywords

Salmonella; Vaccine

Outcome Measures

Primary Outcomes (2)

• To assess the safety and clinical acceptability of CVD 1902 with particular attention to febrile adverse reactions and diarrhea during the first 12 days after inoculation, when administered at a dose of either 10^6, 10^7, 10^8, or 10^9 CFU

  approximately March 2011

• To assess serum antibodies recognizing S. Paratyphi A O polysaccharide and H flagellar antigens, as well as antibody secreting cell (ASC) responses to the O and H antigens as an indication of priming of the mucosal immune system by the vaccine

  approximately April 2011

Secondary Outcomes (4)

• To describe the pattern of fecal shedding of CVD 1902 following vaccination

  approximately March 2011

• To evaluate the CMI responses, with particular emphasis on antigen-specific cytokine production exhibited by peripheral blood mononuclear cells stimulated with soluble antigens, as well as cytotoxic T lymphocytes to S. Paratyphi-infected autologous cells

  approximately March 2011

• To evaluate antigen-specific fecal IgA, serum antibodies with functional bactericidal/opsonophagocytic capacity, and magnitude and persistence of memory T and B cell pools as well as functional genomic and proteomic studies

  approximately April 2011

• To select a well-tolerated and immunogenic dosage level of the vaccine strain for subsequent Phase 2 clinical development

  approximately July 2012

Study Arms (2)

Vaccine-recipients

EXPERIMENTAL

Biological: CVD 1902, a Salmonella enterica Serovar Paratyphi A live, oral vaccine

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

CVD 1902, a Salmonella enterica Serovar Paratyphi A live, oral vaccine BIOLOGICAL

CVD 1902 consists of ΔguaBA, ΔclpX Salmonella enterica serovar Paratyphi A vaccine strain diluted in sterile phosphate buffered saline to achieve the desired inoculum. Form: liquid. Dose: 10\^6, 10\^7, 10\^8, or 10\^9 CFU per mL. Route: oral.

Vaccine-recipients

Placebo OTHER

30 ml of buffer solution (2.0 grams of NaHCO3 dissolved in 150 ml of sterile water) without bacteria, to which food grade corn starch, USP is added, as necessary, to match the turbidity of the vaccine inoculum

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 45 years, inclusive
• Good health as determined by a screening evaluation within 35 days before vaccination
• Able to understand and comply with study requirements
• Provides informed, written consent prior to any study procedures
• Agrees to indefinite storage of unused identifiable clinical specimens at the CVD for use in future research, which may require separate IRB approval
• Agrees not to participate in another investigational vaccine or drug trial during the 6-month study; agrees not to receive a licensed vaccine within 14 days of inoculation (if inactivated) or within 30 days of inoculation (if live attenuated)
• If female, has no childbearing potential, i.e., either surgically sterilized or 1 year postmenopausal, or agrees to abstain from becoming pregnant from the day of screening through Day 56 of the trial by using one of the following methods of birth control: abstinence, intrauterine contraceptive device, oral contraceptives or equivalent hormonal contraception (e.g., progestogen-only implantable, cutaneous hormonal patch, injectable contraceptives, or vaginal hormonal ring), diaphragm or condom in combination with spermicide, or is in a relationship with a vasectomized partner
• Agrees not to donate blood to a blood bank for 12 months after receiving the vaccine

You may not qualify if:

• An acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses (this includes, but is not limited to:
• Diabetes mellitus
• Heart disease (hospitalization for a heart attack or arrhythmia)
• Seizure disorder (febrile seizures as a child \<5 years old or a post-concussive seizure not requiring treatment are acceptable)
• Recurrent infections (\>2 hospitalization for invasive bacterial infections, e.g., pneumonia, meningitis)
• Immunosuppression as a result of underlying illness or treatment with immunosuppressive drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months.
• Active neoplastic disease (or treatment for a neoplastic disease) within past 5 years (excluding non-melanoma skin cancer) or a history of any hematologic malignancy
• Any of the following gastrointestinal conditions:
• History of any of the following types of abdominal surgery:
• Any major gastrointestinal surgery (e.g., intestinal resection or splenectomy)
• Laparotomy (e.g., hysterectomy, Caesarian section, or appendectomy) within the last 3 years
• Laparoscopic abdominal surgery within the past year
• A history of cholelithiasis, cholecystitis, other chronic gall bladder disease or empyema of the gall bladder (these subjects can be included only if gall bladder was surgically removed).
• Crohn's disease, ulcerative colitis, irritable bowel disease, celiac disease, or gastrointestinal ulcers in the past 10 years
• Bleeding in stool (other than small amounts from straining) in past 12 months

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Shin Nippon Biomedical Laboratories (SNBL) Inpatient Facility

Baltimore, Maryland, 21201, United States

Location

University of Maryland, Baltimore Center for Vaccine Development

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Interventions

Vaccines

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Karen L Kotloff, M.D.

  University of Maryland, Baltimore Center for Vaccine Development

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Medicine

Study Record Dates

• First Submitted: May 21, 2010
• First Posted: May 24, 2010
• Study Start: May 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2013
• Last Updated: April 30, 2021

Record last verified: 2021-04

Locations

US (2)