Standard Versus High Dose Inactivated Influenza Vaccine in RA

Rheumatoid Arthritis Clinical Trial

— IV-RA  

Official title:

Improving Influenza Immunization Responses in Rheumatoid Arthritis: A Strategy To Enhance Protection Against A Preventable Cause Of Death In An At Risk Population?

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02936180
• Other study ID #: MP-37-2017-2773
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 2016
• Est. completion date: December 2018

Study information

• Verified date: August 2018
• Source: McGill University Health Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Influenza, a vaccine-preventable respiratory disease, is ranked 8th among the causes of death in the Canadian population. Among rheumatoid arthritis (RA) patients, the incidence of both seasonal influenza and serious influenza-related illness (IRI) are increased. Despite being a high priority group targeted for vaccination, the diagnosis of RA and other patient-specific factors (i.e. older age, treatment, current smoking) are linked to impaired vaccination responses.

Thus the burden of influenza among people with RA is disproportionally high, and interventions to improve responses to influenza vaccination are urgently needed. Strategies to optimize protection in another vulnerable group, the elderly, include the use of quadrivalent vaccines, higher antigen doses, and adjuvants. A high-dose, trivalent, inactivated influenza vaccine (HD-TIV) has recently been shown to have a similar safety profile to standard dose vaccine (SD-TIV) with improved immunogenicity and protection in adults ≥65 years of age. Whether or not analogous strategies to improve responses to influenza vaccine will enhance protection in people with RA is unknown. The investigators hypothesize that the use of the HD-influenza vaccine will improve vaccine-induced protection (i.e. seroconversion and seroprotection) in people with RA compared to SD-influenza vaccine. The investigators propose to conduct a stratified, randomized, modified double blind, active-controlled trial to assess immune responses to two commercial influenza vaccines containing different antigen doses in individuals with RA.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 280
• Est. completion date: December 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Diagnosis of seropositive RA (rheumatoid factor (RF) and/or anti-CCP antibody positive) based on the 2010 ACR-EULAR criteria.

2. At least 6 months of treatment including anti-TNF agents, abatacept, rituximab (dose received within the previous 6 months) and/or methotrexate.

3. Informed consent form signed and dated.

4. Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

1. Vaccination against influenza in the 6 months preceding the trial vaccination.

2. Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to TIV or to a vaccine containing any of the same substances.

3. History of Guillain-Barré syndrome within six weeks of a previous influenza vaccination.

4. Dementia or any other cognitive condition that could interfere with the trial procedures.

5. Thrombocytopenia or bleeding disorder contraindicating IM vaccination (according to treating rheumatologist).

6. Current alcohol abuse or drug addiction.

7. Moderate or severe acute illness with or without fever. If this exists, vaccination will be deferred until the individual has been medically stable and/or afebrile for at least 24 hours.

8. Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve.

9. Pregnant women (the rationale for excluding this group is not their lack of indication for vaccination but the changes of maternal immune responses during pregnancy)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Influenza, Human
• Rheumatoid Arthritis

Intervention

Biological:
• HD-TIV

• SD-QIV

Locations

Country	Name	City	State
Canada	McGill University Health Centre	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
McGill University Health Center	The Arthritis Society, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Performance of the micro-neutralization assay in comparison to the HI assay.		Day 186
Other	Rates of health care use in patients receiving SD- or HD-IV.		Day 186
Primary	Seroconversion rate to HD- versus SD-IV in people with RA	Seroconversion rate (SCR): proportion of subjects in a given treatment group (SD- or HD) with either a =4-fold increase in reciprocal HI titres between D0 and D28 or a rise of undetectable HI titre (i.e. <1:10) pre-vaccination (D0) to an HI titre of =1:40 at D28 post vaccination.	Day 28
Primary	Seroprotection rate to HD- versus SD-IV in people with RA	Seroprotection rate (SPR): the proportion of subjects in a given treatment group attaining a reciprocal HI titre of =1:40 at D28 post-vaccination.	Day 28
Primary	Seroconversion factor in people with RA who received HD- versus SD-IV	Seroconversion factor or GMFR: the geometric mean of the ratio of GMTs (D28/ D0).	Day 28
Primary	Geometric mean titres (GMTs) of HI in people with RA who received HD- versus SD-IV	Geometric mean titres (GMTs) of HI at D0 and D28.	Day 0 and Day 28
Secondary	Durability of HI antibody responses for SD- and HD- IV.		Day 186
Secondary	Rates of side effects during the surveillance period in SD- and HD-IV.		Day 28