Clinical trial NCT03540823: Evaluation of Influenza A/H3N2 Vaccine in Patients With Rheumatologic Diseases
Official title: Immunogenicity and Safety of Influenza A/H3N2 Vaccine in Patients With Rheumatologic Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Systemic Lupus
Sjogren's Syndrome
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2018-05-30
Enrollment: 300
Sex: ALL
Minimum age (years): 9
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Studies in the literature have shown reduced effectiveness of influenza A (H3N2) virus vaccine (20-40%) when compared to A (H1N1) and influenza B. This reduction in efficacy may partly result of the need to propagate A (H3N2) virus into egg components for the preparation of the vaccine. Other factors that may also contribute to the reduction of efficacy against A (H3N2) viruses include the high level of genetic diversity and the rate of rapid evolution of this particular virus subtype and the modification of the immune response to the vaccine secondary of prior infection or vaccination.

Vaccine efficacy studies are required to verify the immunogenicity of the H3N2 influenza vaccine in immunosuppressed patients with rheumatologic disease. In addition, it is relevant to evaluate the safety of the vaccine in this population as well as the possibility of reactivation of the rheumatologic disease itself. The objectives of this study are to evaluate the immunogenicity of the H3N2 component of the inactivated and fragmented influenza vaccine in patients with two systemic autoimmune rheumatic diseases (Systemic Lupus Erythematosus - Adult and Juvenile, Primary Sjögren's Syndrome).

Detailed description: Studies in the literature have shown reduced effectiveness of influenza A (H3N2) virus vaccine (20-40%) when compared to A (H1N1) and influenza B. This reduction in efficacy may partly result of the need to propagate A (H3N2) virus into egg components for the preparation of the vaccine. Other factors that may also contribute to the reduction of efficacy against A (H3N2) viruses include the high level of genetic diversity and the rate of rapid evolution of this particular virus subtype and the modification of the immune response to the vaccine secondary of prior infection or vaccination.

Vaccine efficacy studies are required to verify the immunogenicity of the H3N2 influenza vaccine in immunosuppressed patients with rheumatologic disease. In addition, it is relevant to evaluate the safety of the vaccine in this population as well as the possibility of reactivation of the rheumatologic disease itself. The objectives of this study are to:

1. Evaluate the immunogenicity of the H3N2 component of the inactivated and fragmented influenza vaccine (A / Michigan / 45/2015 (H1N1) pdm09-like virus, A / Singapore / INFIMH-16-0019 / 2016 (H3N2) -like virus; B / Phuket / 3073/2013-like virus\] in patients with two systemic autoimmune rheumatic diseases (Systemic Lupus Erythematosus - Adult and Juvenile, Primary Sjögren's Syndrome).
2. Assess the safety of immunization with the inactivated influenza vaccine \[A / Michigan / 45/2015 (H1N1) pdm09-like virus, A / Singapore / INFIMH-16-0019 / 2016 (H3N2) -like virus; B / Phuket / 3073/2013-like virus\] in these patients with systemic autoimmune rheumatic diseases.
3. Evaluate the possible association between vaccinal immunogenicity with: demographic data, clinical and laboratorial activity of the disease, and treatment of patients with these rheumatic diseases.

Patients with diagnosis of adult and juvenile systemic lupus erythematosus (SLE and JSLE) (n=100) and Sjogren syndrome (SSp) (n=30) according to the classification criteria established for these diseases will be prospectively evaluated at the Hospital das Clínicas of the University of São Paulo (HC-FMUSP).

The control group will consist of 120 healthy individuals who will be recruited into the vaccination campaign paired for age and sex. The juvenile control group will be composed of 50 healthy children who will be recruited in the vaccination campaign paired for age and sex.

Patients and healthy controls will be vaccinated with one dose of the inactivated and fragmented influenza vaccine (A / Michigan / 45/2015 (H1N1) pdm09-like virus, A / Singapore / INFIMH-16-0019 / 2016 (H3N2) -like virus; B / Phuket / 3073/2013-like virus\].

At study entry (D0) and after 30-45 days, blood sample will be collected from patients (SLE, SLE and SSp) and controls.

At entry (D0) and end of study (between D30-D45), patients will be assessed for clinical and laboratory disease activity through specific disease indexes of inflammatory activity: SLE: SLEDAI (lab: blood count, anti-dsDNA, complement, urine I and prot / creat ratio + 1 dry tube for H3N2 serology); SSp: EULAR Sjogren's syndrome disease activity index (Lab: PCR, anti-Ro / SS-A and anti-La / SS-B + 1 dry tube for H3N2 serology).

Patients and healthy controls are advised on possible side effects of the vaccine. In addition, patients and controls are instructed to note in a standardized diary symptoms during study period, such as pruritus, local pain, erythema, induration at the site of the vaccine, fever, chills, headache, myalgia, arthralgia and diarrhea. Signs of airway infections (cough, sputum, sore throat, nasal congestion or expectoration), fever (axillary temperature\> 37.8 °C), need for hospitalizations, severity of infections, sick days, absenteeism at work, and treatment received for infections. Serious adverse events will be defined as those resulting in hospitalization or death. A contact telephone number for patients and controls is provided for guidance on moderate to severe adverse events.

Patients and controls are advised to contact the investigators in case of flu symptoms up to 6 months after vaccination to be evaluated clinically and with nasal swab collection for respiratory virus.

Eligibility criteria: Inclusion Criteria:

* Adult and juvenile systemic lupus erythematosus (SLE) and juvenile SLE patients according to the ACR classification criteria aged ≥ 18 years for adults and aged ≥ 9 and \<18 years for the juvenile group
* Patients with primary Sjögren's Syndrome (SSp) (classification criteria of the European Study Group on Diagnostic Criteria for Sjögren's Syndrome) aged ≥ 18 years

Exclusion Criteria:

1. History of anaphylactic response to vaccine components or egg allergy
2. Moderate or severe acute febrile illness
3. Guillain-Barré syndrome, decompensated heart failure (class III or IV), demyelinating disease.
4. History of live virus vaccine up to 4 weeks before, virus vaccine inactivated up to 2 weeks prior, influenza vaccine up to 6 months prior to study.
5. History of having received blood products up to 6 months prior to the study.
6. Individuals who do not agree to participate in the study and / or whose parents do not agree to participate in the study.
7. Inpatients
8. Patients with severe conditions requiring hospitalization

Primary outcomes:
measure: Number of participants with seroprotection and seroconversion after Influenza vaccine
timeFrame: 30 days
Secondary outcomes:
measure: Number of participants with vaccine-related adverse events as assessed by CTCAE v4.0
timeFrame: 30 days
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Rheumatology Division of Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo
Study officials:
affiliation: Rheumatology Division of Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo São Paulo, Sao Paulo Brazil
name: Eduardo Borba, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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