Adjuvanted Influenza Vaccine in Stem Cell Transplant

NCT ID: NCT02560909

Last Updated: 2017-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2016-08-31

Brief Summary

Influenza virus is an important cause of morbidity in the transplant population and can lead to viral and bacterial pneumonia. Although the annual influenza vaccine is recommended for transplant patients, studies have shown that nonadjuvanted vaccine has poor immunogenicity. There are no studies that define the effect of adjuvanted vaccine in this population. The purpose of this study is to determine if a vaccination with FLUAD® results in improved immunogenicity as compared to standard vaccine in allo-HSCT recipients. Immunogenicity will be assessed by standard quantitative antibody titer assessments and using cell-mediated immunity measurements.

Detailed Description

The investigators plan to study the immunogenicity of two different types of the influenza vaccine in 240 allogeneic stem cell transplant patients during the 2015-2016 season. Patients will be randomized to receive either adjuvanted influenza vaccine or nonadjuvanted. Antibody titers will be evaluated by a standard hemagglutination inhibition assay. The investigators hypothesize that the patients who receive the adjuvanted influenza vaccine will reach significantly higher response to the vaccine. This study advances research on the prevention of serious viral infections in transplant recipients.

Results from this study have the potential to directly improve patient care. If the use of the adjuvanted influenza vaccine is successful, this strategy may lead to a significant reduction in burden of disease, hospitalizations, and long-term morbidity.

The co-administration of vaccine with an adjuvant is a potentially promising method of boosting immunogenicity. Two adjuvants have been used in influenza vaccines: AS03 and MF59. Both are oil-in-water emulsions. AS03 was used in the monovalent pandemic A/H1N1 vaccine in Canada and Europe. Adjuvanted vaccines have been studied in the hematopoietic stem cell transplant population with most studies done in using the AS03-adjuvanted pandemic vaccine. MF59 adjuvant has been used in seasonal influenza vaccine in Canada and Europe for people ≥65 years old. MF59-adjuvanted vaccines have not been well studied in hematopoietic stem cell transplantation but could represent a significant advance if they show greater immunogenicity than the standard non-adjuvanted influenza vaccine. Both FLUAD® and the standard 2015-2016 nonadjuvanted vaccine will contain 15 microgram antigen from each strain and will be injected in a standard dose (0.5 mL) in the deltoid muscle by trained personnel.

Conditions

Transplantation; Influenza Vaccines

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental

The experimental group will receive one dose MF59 adjuvanted intramuscular vaccine.

Group Type: EXPERIMENTAL

FLUAD® influenza vaccine

Intervention Type: BIOLOGICAL

MF59 adjuvant has been used in seasonal influenza vaccine in Canada and Europe for people ≥65 years. MF59 contains squalene, polysorbate 80, and sorbitan trioleate. It is packaged as small microvesicles of 160nm diameter. The complete mechanism of action of MF59 is not well understood but requires activation of the innate immune system; the adjuvant exerts a local inflammatory response increasing the influx of neutrophils and macrophages to the injection site.

Control

The control group will receive one dose of the standard 2015-2016 nonadjuvanted vaccine.

Group Type: ACTIVE_COMPARATOR

FLUVIRAL®

Intervention Type: BIOLOGICAL

Standard 2015-2016 nonadjuvanted vaccine

Interventions

FLUAD® influenza vaccine

MF59 adjuvant has been used in seasonal influenza vaccine in Canada and Europe for people ≥65 years. MF59 contains squalene, polysorbate 80, and sorbitan trioleate. It is packaged as small microvesicles of 160nm diameter. The complete mechanism of action of MF59 is not well understood but requires activation of the innate immune system; the adjuvant exerts a local inflammatory response increasing the influx of neutrophils and macrophages to the injection site.

Intervention Type: BIOLOGICAL

FLUVIRAL®

Standard 2015-2016 nonadjuvanted vaccine

Intervention Type: BIOLOGICAL

Other Intervention Names

MF59 adjuvanted vaccine; Trivalent Influenza Vaccine

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18
• Greater than 3 months post-transplant
• Allogeneic HSCT

Exclusion Criteria

• Has already received influenza vaccination for 2015-2016 season
• Egg allergy
• Previous life-threatening reaction to influenza vaccine (i.e. Guillain Barre Syndrome)
• Febrile illness in the past one week
• Receipt of intravenous immunoglobulin (IVIG) in the past 30 days or planning to receive IVIG in the next 4 weeks
• Unable to provide informed consent
• Unable to comply with study protocol

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

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Deepali Kumar

Physician, Transplant Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Deepali Kumar, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Other Identifiers

15-9503

Identifier Type: -

Identifier Source: org_study_id