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

Immunosuppression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00213265
• Other study ID #: 0020020011
• Status: Completed
• Phase: Phase 3
• Start date: July 2002
• Est. completion date: February 2017

Study information

• Verified date: February 2021
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Immunosuppression
• Organ Transplant

Intervention

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.
• 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

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	Serious vaccine related adverse events		7 days post-vaccination
Secondary	Nature of immune suppression		24-28 weeks
Secondary	Presence of bacterial, viral or other opportunistic infections		24-28 weeks
Secondary	Presence of rejection after enrollment		24-28 weeks
Secondary	Presence of concurrent diseases or conditions including alterations of renal, hepatic, cardiac and bowel function		24-28 weeks