Pneumococcal Vaccination of Fiji Infants

October 20, 2008 updated by: University of Melbourne

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

552

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Fiji
      • Suva, Fiji
        • Colonial War Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 1 month (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
PCV at 6 weeks, 10 weeks, and 14 weeks; PPS at 18 months
Biological: Pneumovax 23
23-valent PPS, 25 micrograms/serotype
Biological: Prevnar
7-valent PCV, 2 micrograms/serotype, except serotype 6B which is 4 micrograms/serotype
Experimental: B
PCV at 6 weeks, 10 weeks, and 14 weeks; PPS at 12 months and 18 months
Biological: Pneumovax 23
23-valent PPS, 25 micrograms/serotype
Biological: Prevnar
7-valent PCV, 2 micrograms/serotype, except serotype 6B which is 4 micrograms/serotype
Experimental: C
PCV at 6 weeks and 14 weeks; PPS at 18 months
Biological: Pneumovax 23
23-valent PPS, 25 micrograms/serotype
Biological: Prevnar
7-valent PCV, 2 micrograms/serotype, except serotype 6B which is 4 micrograms/serotype
Experimental: D
PCV at 6 weeks and 14 weeks; PPS at 12 months and 18 months
Biological: Pneumovax 23
23-valent PPS, 25 micrograms/serotype
Biological: Prevnar
7-valent PCV, 2 micrograms/serotype, except serotype 6B which is 4 micrograms/serotype
Experimental: E
PCV at 14 weeks; PPS at 18 months
Biological: Pneumovax 23
23-valent PPS, 25 micrograms/serotype
Biological: Prevnar
7-valent PCV, 2 micrograms/serotype, except serotype 6B which is 4 micrograms/serotype
Experimental: F
PCV at 14 weeks; PPS at 12 months and 18 months
Biological: Pneumovax 23
23-valent PPS, 25 micrograms/serotype
Biological: Prevnar
7-valent PCV, 2 micrograms/serotype, except serotype 6B which is 4 micrograms/serotype
Experimental: G
No PCV; PPS at 12 months and 18 months
Biological: Pneumovax 23
23-valent PPS, 25 micrograms/serotype
Active Comparator: H
No PCV; PPS at 18 months
Biological: Pneumovax 23
23-valent PPS, 25 micrograms/serotype

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
19 months of age

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
18 months of age
Rate of decline: assessment of antibody levels
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Melbourne

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Fiona M Russell, FRACP, University of Melbourne

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

January 1, 2008

Study Completion (Actual)

August 1, 2008

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Estimate)

October 21, 2008

Last Update Submitted That Met QC Criteria

October 20, 2008

Last Verified

October 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-042 (Fox Chase Cancer Center)
  • FNRERC Reference # 2002-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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