Clinical trial NCT00342628: Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Typhoid Fever
Keywords: Antibody
Reactions
Vaccine
Conjugate Vaccine
Typhoid Fever
Trial
Safety
Immunogenicity
Comparability
DTP
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2006-06-21
Enrollment: 301
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Infants With Adverse Reactions After Vaccination
timeFrame: at 2, 4, 6 and 12 months
Secondary outcomes:
measure: IgG Anti-Vi Levels
timeFrame: cord sera, infants' sera at 7, 12 and 13 months
measure: Antibody Responses to Tetanus Toxoid, Diphtheria Toxoid, and Pertussis Toxin
timeFrame: Cord sera, and infants' sera at 7, 12 and 13 months of age
measure: Antibody Responses to Hib CP
timeFrame: Cord sera and infant sera at 7, 12, and 13 months
Other outcomes:
Locations:
city: Viet Tri
country: Vietnam
facility: Thanh Thuy District Health Center
state: Phu Tho Province
Study officials:
affiliation: PDMI, NICHD, NIH
name: Feng-Ying (Kimi) Lin, MD, MPH
role: STUDY_DIRECTOR
References:
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