Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00342628
Recruitment Status : Completed
First Posted : June 21, 2006
Results First Posted : June 27, 2012
Last Update Posted : June 27, 2012
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Tracking Information
First Submitted Date  ICMJE June 19, 2006
First Posted Date  ICMJE June 21, 2006
Results First Submitted Date  ICMJE March 30, 2012
Results First Posted Date  ICMJE June 27, 2012
Last Update Posted Date June 27, 2012
Study Start Date  ICMJE July 2006
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2012)
Number of Infants With Adverse Reactions After Vaccination [ Time Frame: at 2, 4, 6 and 12 months ]
Number of infants with Fever>=38.0 C, Induration>=2.5cm at DTP site, Induration>=2.5cm,Vi-rEPA/Hib-TT site, Erythema>=2.5cm, at DTP site, Erythema>=2.5cm, Vi-rEPA/Hib-TT site, Inconsolable crying<4hr, Inconsolable crying>=4hr per injection with Vi conjugate vaccine given in conjunction with DTP in infants.
Original Primary Outcome Measures  ICMJE
 (submitted: June 19, 2006)
Routine typhoid vaccine administered along with DTP.
Change History Complete list of historical versions of study NCT00342628 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2012)
  • IgG Anti-Vi Levels [ Time Frame: cord sera, infants' sera at 7, 12 and 13 months ]
    IgG anti-Vi was measured by ELISA and expressed as ELISA units (EU)in all sera.
  • Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin [ Time Frame: Cord sera, and infants' sera at 7, 12 and 13 months of age ]
    IgG anti-diphtheria toxoid (DT), -tetanus toxoid (TT) and -pertussis toxin (PT) were measured by ELISA in sera of 30 randomly chosen infants per group.
  • Antibody Responses to Hib CP [ Time Frame: Cord sera and infant sera at 7, 12, and 13 months ]
    IgG anti-Hib CP was measured by ELISA in sera of 30 randomly chosen infants per group
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants
Official Title  ICMJE Evaluation of the Safety, Immunogenicity and Compatibility With DTP of an Investigational Vi-rEPA Conjugate Vaccine for Typhoid Fever When Administered to Infants in Vietnam Concurrently With DTP
Brief Summary

The purpose of this study is to evaluate the safety, immunogenicity, and compatibility of our Vi-rEPA conjugate administered to infants with their routine vaccinations.

We propose to recruit 300 full term healthy newborns in Vietnam and randomly divide them to receive Vi-rEPA plus DTP, Hib-TT (not yet used in Vietnam) plus DTP, or DTP alone. Consent is obtained following interviews of mothers during prenatal visits, or after delivery. All vaccines will be administered at 2, 4, and 6 months. A booster of Vi-rEPA or Hib-TT conjugate will be administered at 12 months of age and reactions monitored at 6, 24 and 48 hours after each injection. Maternal and cord blood samples are collected during labor and at delivery. Blood will be taken at 7, and 12 months of age from all study infants and at 13 months from infants injected with Vi-rEPA or with Hib-TT at 12 months. The blood samples will be assayed for Vi, Hib, diphtheria, tetanus and pertussis antibodies.

The levels of serum IgG anti-Vi elicited by Vi-rEPA administered to infants by the above schedule will be compared to those elicited by this vaccine in 2 to 5 year-olds in the efficacy trial conducted in Dong Thap Province, Vietnam.

Detailed Description

Typhoid fever remains common, serious, and difficult-to-treat throughout the world including Vietnam. Limitations of the three licensed typhoid vaccines have prevented their use for routine vaccination of infants. The most recent, Vi polysaccharide typhoid vaccine is useful only in individuals greater than or equal to 5 years of age because of its age-related and T-cell independent properties. The immunogenicity of Vi in individuals less than 5 years-old has been improved by binding it to a protein. In 2 to 4-year-olds, 2 injections of the Vi conjugate induced higher levels of serum IgG anti-Vi than Vi in 5 to 14-year-olds.

A double-blind, placebo controlled and randomized efficacy study in 2 -to-5 years old children in Vietnam showed an over-all efficacy after 27 months of active surveillance followed by 19 months of passive surveillance of 89%. Subsequently a dosage study in the same age group showed the highest antibody levels were induced by the 25 mcg dose.

Now we wish to evaluate the safety, immunogenicity, and compatibility of our Vi-rEPA conjugate administered to infants with their routine vaccinations.

We propose to recruit 300 full term healthy newborns in Vietnam and randomly divide them to receive Vi-rEPA plus DTP (Group A), Hib-TT (not yet used in Vietnam) plus DTP (Group B), or DTP alone (Group C). Maternal and cord blood are taken routinely on all deliveries in Vietnam; these sera will be retrieved for storage when consent is obtained following interviews of mothers during prenatal visits, or after delivery. All vaccines will be administered at 2, 4, and 6 months. A booster of Vi-rEPA or Hib-TT conjugate will be administered at 12 months of age and reactions monitored at 6, 24 and 48 hours after each injection. Blood will be taken at 7, and 12 months of age from all study infants and at 13 months from infants injected with Vi-rEPA or with Hib-TT at 12 months. The blood samples will be assayed for Vi, Hib, diphtheria, tetanus and pertussis antibodies.

The levels of serum IgG anti-Vi elicited by Vi-rEPA administered to infants by the above schedule will be compared to those elicited by this vaccine in 2 to 5 year-olds in the efficacy trial conducted in Dong Thap.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Typhoid Fever
Intervention  ICMJE
  • Biological: Vi-rEPA conjugate vaccine for typhoid fever
    Vi-rEPA contains a 25 ug/dose of Vi (Sanofi-Pasteur Lot 130) and rEPA in 0.2 N NaCl, 10 mM phosphate PH 7.2 and 0.01% thimerosal.
    Other Name: Vi conjugate
  • Biological: Hib-TT
    Hib-TT is Hemophilus influenzae type b-tetanus toxoid conjugate vaccine (ActHib, NDC#49281-545-05 Sanofi-Pasteur, France) in single-dose vials containing 10 ugof Hib CP conjugated to 24 ug of tetanus toxoid
    Other Name: Hib conjugate
  • Biological: DTP
    DTP, diphtheria, tetanus toxoid and pertussis vaccine were from the Ministry of Health, Vietnam for routine infant immunization
    Other Name: EPI vaccine
Study Arms  ICMJE
  • Experimental: Vi-rEPA plus DTP
    Vi-rEPA and DTP at 2, 4, 6 months, and Vi-rEPA at 12 months
    Interventions:
    • Biological: Vi-rEPA conjugate vaccine for typhoid fever
    • Biological: DTP
  • Active Comparator: Hib-TT plus DTP
    Hib-TT and DTP at 2,4 and 6 months, Hib-TT at 12 months
    Interventions:
    • Biological: Hib-TT
    • Biological: DTP
  • Active Comparator: EPI
    DTP at 2,4 and 6 months
    Intervention: Biological: DTP
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 22, 2012)
301
Original Enrollment  ICMJE
 (submitted: June 19, 2006)
300
Actual Study Completion Date  ICMJE January 2011
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Healthy full-term newborns.
  • Birth weights of >=2500 grams.

Exclusion criteria:

  • Newborns without maternal and cord blood samples
  • Newborns born to mothers with serious medical problems.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Vietnam
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00342628
Other Study ID Numbers  ICMJE 999999050
OH99-CH-N050 ( Registry Identifier: NICHD IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
Study Sponsor  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Feng-Ying (Kimi) Lin, MD, MPH PDMI, NICHD, NIH
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP