Clinical Trial: Pneumococcal Vaccination of Fiji Infants

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Single-Blind Open-Label Randomized Phase II Study of the Safety, Immunogenicity and Impact on Pneumococcus (Pnc) Carriage of the Pnc Vaccination Regimens Combining 1, 2, or 3 Doses of 7-Valent Pneum

Brief Summary: Pneumonia is the most common reason for admission of Fijian children to hospitals. The most common germ causing pneumonia is "streptococcus pneumoniae." It is a common cause of meningitis (infection around the brain and spinal cord), ear infections, and blood infections and it lives in the nose of humans. A vaccine has been developed that will help prevent these common diseases but prevents only about one quarter of pneumonia cases and it is expensive. This study explores new ways of giving this vaccine that are affordable, safe, and effective in countries such as Fiji. About 550 Fijian infants presenting at 6 weeks of age, for their first diptheria, tetanus, toxoid, pertussis vaccine immunization, to one of the participating Health Centers or Colonial War Memorial Hospital in urban Suva, Fiji will be enrolled. Children will remain in the study for 2 years. Study procedures include full vaccination against 7 types of pneumococcus, blood tests, and nasal swabs.

Detailed Summary: This research project began as a study of alternative strategies for Pnc (Pneumococcus) immunization for children in developing countries. In the original study, infants presenting to a health center in urban Fiji were randomized to receive 1, 2, or 3 doses of PCV (Prevnar) followed by a dose of 23-valent PPS (Pneumococcal polysaccharide vaccine) at 6 or 9 months of age. The regimens were compared with each other and with 2 control groups with respect to immunogenicity, impact on carriage of vaccine type Pnc, and response to a small dose of PPS at 15 months of age. After the trial was underway and 228 infants had been recruited, concerns were raised about the safety of PPS in infancy. Specifically concerns were raised that it might result in later immunological hyporesponsiveness in some of the recipients, to some of the serotypes. After a thorough review it was decided to proceed with the study, but to modify it so that it addressed directly the issue of potential hyporesponsiveness, while not giving PPS to any children under 12 months of age. This protocol represents the completion of the study with the new design for the children already enrolled, and a new design for a further cohort of children who will be enrolled. The newly designed trial will be a single blind, open-label, randomized, controlled trial of 550 healthy infants. Infants will be randomized to 1 of 8 equal groups to receive 0, 1, 2, or 3 doses of PCV (Pneumococcal conjugate vaccine), with or without a booster of PPS at 12 months of age. Two control groups will be recruited, 1 will receive no PCV in infancy and the other will receive a dose of PPS at 12 months of age. At 18 months of age, all infants will receive a 20 percent dose of PPS to stimulate and allow the assessment of immunological memory. At 2 years of age, any child who has received no or one dose of PCV (Groups E, F, G and H) will receive a single dose of PCV. Blood samples will be taken at 18 weeks age, 12 months of age, before the 18
Sponsor: University of Melbourne

Current Primary Outcome: For each serotype assayed (23 for ELISA and 11 for functional assays) the proportion of children responding to the micro-PPS dose at 18 months and the GMC of the response will be compared between children who receive PPS at 12 months and those who do not [ Time Frame: 19 months of age ]

Original Primary Outcome:

Current Secondary Outcome:

  • Proportion of children showing hyporesponse at 18 months to more than half of all 23 serotypes [ Time Frame: 18 weeks; 12.5 months of age ]
  • Immunogenicity and carriage: Immune responses following the primary series of conjugate vaccination, measured by ELISA and OPA will be compared between the group receiving two doses of PCV and those receiving 3 doses of vaccine [ Time Frame: 18 months of age ]
  • Rate of decline: assessment of antibody levels [ Time Frame: 12 months ]


Original Secondary Outcome:

Information By: University of Melbourne

Dates:
Date Received: September 13, 2005
Date Started: November 2005
Date Completion:
Last Updated: October 20, 2008
Last Verified: October 2008