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

Safety and Immunogenicity of 7-Valent Pneumococcal Conjugate Vaccine Among Solid Organ Transplant Recipients: Protocol 1A and 1B

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.

Study Overview

• Status: Completed
• Conditions: Immunosuppression; Organ Transplant
• Intervention / Treatment: Biological: Pneumococcal 7-valent Conjugate Vaccine; Biological: 7-valent pneumococcal conjugate vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2	Biological: 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.; Other Names: Prevnar
Active Comparator: 1	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; Other Names: Prevnar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Geometric Mean Concentration of pneumococcal antibodies	Transplant patients: at baseline, just before dose 3, and 6-8 weeks after dose 3; Controls: at baseline, just before dose 3, and 6-8 weeks after dose 3. For those whose series consisted of 1 or 2 doses, at baseline, and 6-8 weeks after doses 1 and 2.
Serious vaccine related adverse events	7 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Nature of immune suppression	24-28 weeks
Presence of bacterial, viral or other opportunistic infections	24-28 weeks
Presence of rejection after enrollment	24-28 weeks
Presence of concurrent diseases or conditions including alterations of renal, hepatic, cardiac and bowel function	24-28 weeks

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Upton Allen, MD, The Hospital for Sick Children, Toronto Canada; Study Chair: Upton Allen, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2002
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Actual): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: pediatrics; immunosuppression; vaccine; organ transplantation; pneumococcal conjugate vaccine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 0020020011