Pneumococcal Vaccination of Fiji Infants

Pneumococcal Infections Clinical Trial

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 Pneumococcal Conjugate Vaccine (PCV) in the First 4 Months of Life Followed by a Single Dose of 23-Valent Pneumococcal Polysaccharide Vaccine (PPS) at 12 Months of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00170612
• Other study ID #: 03-042
• Secondary ID: FNRERC Reference
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2005
• Last updated: October 20, 2008
• Start date: November 2005
• Est. completion date: August 2008

Study information

• Verified date: October 2008
• Source: University of Melbourne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Fiji: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Description:

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 months dose and 4 weeks later. In addition half of the children will have a blood sample taken at 9 months and the other half will have a sample taken 2 weeks after their 12 month dose of PPS. The 9- and 12-month blood sample will assess the long-term persistence of circulating antibody and avidity maturation following a 1, 2, or 3 dose primary series of PCV. The primary objective is to demonstrate noninferiority at 19 months of age, of those groups receiving PPS at 12 months and those who do not with respect to the proportion of children in each group, with a satisfactory immune response at 19 months of age, measured by OPA to each of the 11 serotypes included in the PPS for which an OPA has been developed. The secondary objective is to assess the immunogenicity and impact on carriage of various Pnc vaccination regimens that combine 1 to 3 doses of PCV with a dose of PPS, concerns regarding the potential for the development of hyporesponsiveness. Endpoints to be evaluated will include serotype specific immunoglobulin G antibody measured by enzyme-linked immunosorbent assay to the 23 serotypes in the PPS, avidity assays to the same serotypes, opsonophagocytic assays to the 11 serotypes for which these assays are currently available, and Pnc carriage by serotype. With hyporesponsiveness as the primary endpoint of interest a scheme of analysis has been proposed which will require a minimum sample size of 500.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 552
• Est. completion date: August 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Weeks to 8 Weeks

Eligibility

Inclusion Criteria:

1. Healthy infant aged between 6 and 8 weeks

2. No significant maternal or perinatal history

3. Written and signed parental/caregiver consent

4. Lives within 30 minutes of the health clinic

5. Family anticipate living in the study area for the next 2 years

Exclusion Criteria:

1. Known allergy to any component of the vaccine

2. Allergic reaction or anaphylactoid reaction with previous vaccines

3. Known immunodeficiency disorder

4. HIV positive mother (many women are tested for HIV antenatally, however a test is not planned; therefore it would be based on clinic records or self report)

5. Known thrombocytopenia or coagulation disorder

6. On immunosuppressive medication

7. Received any blood product since birth

8. Severe congenital anomaly

9. Chronic or progressive disease

10. Seizure disorder

11. History of invasive Pneumococcal, meningococcal, or Haemophilus influenzae diseases

12. Moderate or severe acute infection (temporary exclusion); Minor illnesses such as an uncomplicated upper respiratory tract infection, localized skin infections, or mild diarrhea will not be an exclusion criterion

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

Biological:
• Pneumovax 23
23-valent PPS, 25 micrograms/serotype
• Prevnar
7-valent PCV, 2 micrograms/serotype, except serotype 6B which is 4 micrograms/serotype

Locations

Country	Name	City	State
Fiji	Colonial War Memorial Hospital	Suva

Sponsors (2)

Lead Sponsor	Collaborator
University of Melbourne	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Fiji, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		19 months of age	No
Secondary	Proportion of children showing hyporesponse at 18 months to more than half of all 23 serotypes		18 weeks; 12.5 months of age	No
Secondary	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		18 months of age	No
Secondary	Rate of decline: assessment of antibody levels		12 months	No