Safety and Immunogenicity of 7-Valent Pneumococcal Conjugate Vaccine in Children Receiving Solid Organ Transplants

NCT ID: NCT00213265

Last Updated: 2021-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-07-31
• Study Completion Date: 2017-02-28

Brief Summary

We plan to study whether the 7-valent pneumococcal conjugate vaccine (Prevnar™) is safe and effective in protecting children who have had a solid organ transplantation and healthy children from pneumococcal infections.

We expect that two or more doses of Prevnar™ will result in similar antibody responses among transplant recipients compared with healthy control subjects, and that children who have undergone solid organ transplant will have a similar number of serious vaccine-related adverse events within 7 days after Prevnar™ as the healthy patients.

Detailed Description

Solid organ transplantation (SOT) has emerged as a lifesaving therapy for many patients with end organ failure. SOT recipients have a lifelong increased risk for infections as a result of immunosuppression, including those caused by pneumococci. The increased susceptibility to pneumococcal infections is multi-factorial and is related to underlying immunosuppression as well as varying degrees of splenic dysfunction as a result of underlying pretransplantation diseases, among other factors.

The types and severity of invasive pneumococcal disease vary among each transplant population. However, comparative data are lacking. Lung transplant recipients have the highest incidence of bacterial pneumonia among solid organ transplant recipients. Pneumonia secondary to Streptococcus pneumoniae occurs in heart transplant patients at a rate 10 times that found in the general population. It is suggested that besides the intensity of immunosuppression, ongoing immunosuppression is important as a risk factor for invasive pneumococcal disease in transplant recipients.

Despite the fact that 23-valent polysaccharide pneumococcal vaccine is one of the vaccines that receives priority among organ transplant recipients, at the Hospital for Sick Children, several cases of pneumococcal disease have been seen. The advent of the 7-valent conjugate vaccine affords the opportunity to possibly reduce the burden of pneumococcal disease in the patient population by virtue that it may be more immunogenic in transplant patients

This study will examine the antibody titres achieved among transplant recipients who are immunized with Prevnar™, as well as evaluate the safety and tolerability or Prevnar™ administered as a three-dose regimen to children and adolescents following organ transplantation.

Conditions

Organ Transplant; Immunosuppression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

Pneumococcal 7-valent Conjugate Vaccine

Intervention Type: BIOLOGICAL

Healthy infants: The Prevnar schedule for healthy infants consists of 3 doses of 0.5 ml each, at approximately 2 month intervals, followed by a fourth dose of 0.5 ml at 12-15 months of age (i.e., 2, 4, 6, and 12-15 months)

Previously unvaccinated older infants and children, who are beyond the age of the routine infant schedule, should receive the follwong schedule:

7-11 months of age: 3 doses (2 doses at least 4 weeks apart with the third dose after the first birthday and separated from the second dose by at least two months)

12-23 months of age: 2 doses (at least 2 months apart)

≥24 months through 9 years of age: 1 dose

2

Group Type: EXPERIMENTAL

7-valent pneumococcal conjugate vaccine

Intervention Type: BIOLOGICAL

For transplant patients, vaccination will be started at 4 months or greater after transplantation. The second dose will be given 8 weks following the frist, the third dose 8 weeks after the second, and the fourth will be given 8 weeks after the third.

Interventions

7-valent pneumococcal conjugate vaccine

For transplant patients, vaccination will be started at 4 months or greater after transplantation. The second dose will be given 8 weks following the frist, the third dose 8 weeks after the second, and the fourth will be given 8 weeks after the third.

Intervention Type: BIOLOGICAL

Pneumococcal 7-valent Conjugate Vaccine

Healthy infants: The Prevnar schedule for healthy infants consists of 3 doses of 0.5 ml each, at approximately 2 month intervals, followed by a fourth dose of 0.5 ml at 12-15 months of age (i.e., 2, 4, 6, and 12-15 months)

Previously unvaccinated older infants and children, who are beyond the age of the routine infant schedule, should receive the follwong schedule:

7-11 months of age: 3 doses (2 doses at least 4 weeks apart with the third dose after the first birthday and separated from the second dose by at least two months)

12-23 months of age: 2 doses (at least 2 months apart)

≥24 months through 9 years of age: 1 dose

Intervention Type: BIOLOGICAL

Other Intervention Names

Prevnar; Prevnar

Eligibility Criteria

Inclusion Criteria

Transplant recipients:

• Children 4 months of age up to 18 years of age
• received a kidney, liver, heart, lung or other solid organ transplantation in a Canadian transplant centre
• Informed consent obtained

Healthy Infants and Children:

• Children 2 months to 9 years of age
• no underlying chronic medical conditions
• Informed consent obtained

Exclusion Criteria

• Previous immunization with pneumococcal vaccine.
• Known hypersensitivity to any of the components of the vaccine, including diphtheria toxoid. Besides the saccharides and CRM197 carrier protein, the vaccine contains aluminum phosphate adjuvant.
• Any significant infection and/or fever at the time of vaccination
• Major acute illness such as clinical instability and acute graft rejection
• Latex allergy

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Upton Allen

Chief, Division of Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Upton Allen, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children, Toronto Canada

Upton Allen

Role: STUDY_CHAIR

The Hospital for Sick Children

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

0020020011

Identifier Type: -

Identifier Source: org_study_id