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

NCT ID: NCT00342628

Last Updated: 2012-06-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

301 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-07-31

Study Completion Date

2011-01-31

Brief Summary

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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

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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.

Conditions

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Typhoid Fever

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Vi-rEPA plus DTP

Vi-rEPA and DTP at 2, 4, 6 months, and Vi-rEPA at 12 months

Group Type EXPERIMENTAL

Vi-rEPA conjugate vaccine for typhoid fever

Intervention Type BIOLOGICAL

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.

DTP

Intervention Type BIOLOGICAL

DTP, diphtheria, tetanus toxoid and pertussis vaccine were from the Ministry of Health, Vietnam for routine infant immunization

Hib-TT plus DTP

Hib-TT and DTP at 2,4 and 6 months, Hib-TT at 12 months

Group Type ACTIVE_COMPARATOR

Hib-TT

Intervention Type BIOLOGICAL

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

DTP

Intervention Type BIOLOGICAL

DTP, diphtheria, tetanus toxoid and pertussis vaccine were from the Ministry of Health, Vietnam for routine infant immunization

EPI

DTP at 2,4 and 6 months

Group Type ACTIVE_COMPARATOR

DTP

Intervention Type BIOLOGICAL

DTP, diphtheria, tetanus toxoid and pertussis vaccine were from the Ministry of Health, Vietnam for routine infant immunization

Interventions

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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.

Intervention Type 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

Intervention Type BIOLOGICAL

DTP

DTP, diphtheria, tetanus toxoid and pertussis vaccine were from the Ministry of Health, Vietnam for routine infant immunization

Intervention Type BIOLOGICAL

Other Intervention Names

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Vi conjugate Hib conjugate EPI vaccine

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Feng-Ying (Kimi) Lin, MD, MPH

Role: STUDY_DIRECTOR

PDMI, NICHD, NIH

Locations

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Thanh Thuy District Health Center

Việt Trì, Phu Tho, Vietnam

Site Status

Countries

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Vietnam

References

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Acharya IL, Lowe CU, Thapa R, Gurubacharya VL, Shrestha MB, Cadoz M, Schulz D, Armand J, Bryla DA, Trollfors B, et al. Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report. N Engl J Med. 1987 Oct 29;317(18):1101-4. doi: 10.1056/NEJM198710293171801.

Reference Type BACKGROUND
PMID: 3657877 (View on PubMed)

Crump JA, Mintz ED. Global trends in typhoid and paratyphoid Fever. Clin Infect Dis. 2010 Jan 15;50(2):241-6. doi: 10.1086/649541.

Reference Type BACKGROUND
PMID: 20014951 (View on PubMed)

Gilman RH, Terminel M, Levine MM, Hernandez-Mendoza P, Hornick RB. Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet. 1975 May 31;1(7918):1211-3. doi: 10.1016/s0140-6736(75)92194-7.

Reference Type BACKGROUND
PMID: 48834 (View on PubMed)

Klugman KP, Gilbertson IT, Koornhof HJ, Robbins JB, Schneerson R, Schulz D, Cadoz M, Armand J. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet. 1987 Nov 21;2(8569):1165-9. doi: 10.1016/s0140-6736(87)91316-x.

Reference Type BACKGROUND
PMID: 2890805 (View on PubMed)

Kossaczka Z, Lin FY, Ho VA, Thuy NT, Van Bay P, Thanh TC, Khiem HB, Trach DD, Karpas A, Hunt S, Bryla DA, Schneerson R, Robbins JB, Szu SC. Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam. Infect Immun. 1999 Nov;67(11):5806-10. doi: 10.1128/IAI.67.11.5806-5810.1999.

Reference Type BACKGROUND
PMID: 10531232 (View on PubMed)

Mai NL, Phan VB, Vo AH, Tran CT, Lin FY, Bryla DA, Chu C, Schiloach J, Robbins JB, Schneerson R, Szu SC. Persistent efficacy of Vi conjugate vaccine against typhoid fever in young children. N Engl J Med. 2003 Oct 2;349(14):1390-1. doi: 10.1056/NEJM200310023491423. No abstract available.

Reference Type BACKGROUND
PMID: 14523155 (View on PubMed)

Levine MM, Ferreccio C, Abrego P, Martin OS, Ortiz E, Cryz S. Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine. 1999 Oct 1;17 Suppl 2:S22-7. doi: 10.1016/s0264-410x(99)00231-5.

Reference Type BACKGROUND
PMID: 10506405 (View on PubMed)

Lin FY, Vo AH, Phan VB, Nguyen TT, Bryla D, Tran CT, Ha BK, Dang DT, Robbins JB. The epidemiology of typhoid fever in the Dong Thap Province, Mekong Delta region of Vietnam. Am J Trop Med Hyg. 2000 May;62(5):644-8. doi: 10.4269/ajtmh.2000.62.644.

Reference Type BACKGROUND
PMID: 11289678 (View on PubMed)

Lin FY, Ho VA, Khiem HB, Trach DD, Bay PV, Thanh TC, Kossaczka Z, Bryla DA, Shiloach J, Robbins JB, Schneerson R, Szu SC. The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. N Engl J Med. 2001 Apr 26;344(17):1263-9. doi: 10.1056/NEJM200104263441701.

Reference Type BACKGROUND
PMID: 11320385 (View on PubMed)

Ochiai RL, Acosta CJ, Danovaro-Holliday MC, Baiqing D, Bhattacharya SK, Agtini MD, Bhutta ZA, Canh DG, Ali M, Shin S, Wain J, Page AL, Albert MJ, Farrar J, Abu-Elyazeed R, Pang T, Galindo CM, von Seidlein L, Clemens JD; Domi Typhoid Study Group. A study of typhoid fever in five Asian countries: disease burden and implications for controls. Bull World Health Organ. 2008 Apr;86(4):260-8. doi: 10.2471/blt.06.039818.

Reference Type BACKGROUND
PMID: 18438514 (View on PubMed)

Sinha A, Sazawal S, Kumar R, Sood S, Reddaiah VP, Singh B, Rao M, Naficy A, Clemens JD, Bhan MK. Typhoid fever in children aged less than 5 years. Lancet. 1999 Aug 28;354(9180):734-7. doi: 10.1016/S0140-6736(98)09001-1.

Reference Type BACKGROUND
PMID: 10475185 (View on PubMed)

Szu SC, Stone AL, Robbins JD, Schneerson R, Robbins JB. Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals. J Exp Med. 1987 Nov 1;166(5):1510-24. doi: 10.1084/jem.166.5.1510.

Reference Type BACKGROUND
PMID: 3681191 (View on PubMed)

Taylor DN, Levine MM, Kuppens L, Ivanoff B. Why are typhoid vaccines not recommended for epidemic typhoid fever? J Infect Dis. 1999 Dec;180(6):2089-90. doi: 10.1086/315159. No abstract available.

Reference Type BACKGROUND
PMID: 10558978 (View on PubMed)

Other Identifiers

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OH99-CH-N050

Identifier Type: REGISTRY

Identifier Source: secondary_id

999999050

Identifier Type: -

Identifier Source: org_study_id

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