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Systemic LupusPhase 4NCT03540823

Evaluation of Influenza A/H3N2 Vaccine in Patients With Rheumatologic Diseases

A Phase 4 study testing 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 people with Systemic Lupus and Sjogren's Syndrome, run by University of Sao Paulo General Hospital at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 9 years and olderHealthy volunteers can take part
Conditions the study is for
Systemic Lupus, Sjogren's Syndrome
What is being tested?
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)
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
300 participants
Where
1 siteBrazil
Study dates
23 Apr 2018to 23 Aug 2018
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 9 years and older
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Brazil1 site
  • Rheumatology Division of Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo

    São Paulo, 05403-000

Other trials in Brazil

About this study

Official title: Immunogenicity and Safety of Influenza A/H3N2 Vaccine in Patients With Rheumatologic Diseases

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).

Read the 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.

Being tested
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)
Medical subject headings
Sjogren's Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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)Biological

    Single dose of 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)

Study groups in NCT03540823
Study groupRoleWhat they receive
Patients with rheumatic diseasesExperimentalPatients with diagnosis of adult and juvenile systemic lupus erythematosus (SLE and JSLE) and Sjogren syndrome (SSp)
Receives: Biological: 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)
Healthy controlsOtherHealthy children and adults
Receives: Biological: 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)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with seroprotection and seroconversion after Influenza vaccine

    Immunogenicity (seroprotection and seroconversion) 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) will be evaluated by haemagglutination inhibition (HI) assay

    Measured: 30 days

Secondary outcomes (1)
  1. Number of participants with vaccine-related adverse events as assessed by CTCAE v4.0

    Patients and healthy controls are instructed to note all symptoms in a standardized diary 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. Number of participants with vaccine-related adverse events will be assessed by CTCAE v4.0 and the following reference: "Saad CG, Borba EF, Aikawa NE, et al. Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases. Ann Rheum Dis. 2011;70:1068-73."

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2018
  2. Study start23 Apr 2018
  3. Primary completion23 Jun 2018
  4. Study completion23 Aug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
300 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03540823
Sponsor's protocol ID
H3N2VaccineReumatoHC
Status last verified
Apr 2018
First submitted
14 May 2018
Last updated
26 Apr 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Silva CA, Aikawa NE, Bonfa E. Vaccinations in juvenile chronic inflammatory diseases: an update. Nat Rev Rheumatol. 2013 Sep;9(9):532-43. doi: 10.1038/nrrheum.2013.95. Epub 2013 Jul 2.

    PubMed 23820860
  • Pasoto SG, Ribeiro AC, Bonfa E. Update on infections and vaccinations in systemic lupus erythematosus and Sjogren's syndrome. Curr Opin Rheumatol. 2014 Sep;26(5):528-37. doi: 10.1097/BOR.0000000000000084.

    PubMed 25022358
  • Kuruma KA, Borba EF, Lopes MH, de Carvalho JF, Bonfa E. Safety and efficacy of hepatitis B vaccine in systemic lupus erythematosus. Lupus. 2007;16(5):350-4. doi: 10.1177/0961203307078225.

    PubMed 17576737
  • Aikawa NE, Franca IL, Ribeiro AC, Sallum AM, Bonfa E, Silva CA. Short and long-term immunogenicity and safety following the 23-valent polysaccharide pneumococcal vaccine in juvenile idiopathic arthritis patients under conventional DMARDs with or without anti-TNF therapy. Vaccine. 2015 Jan 29;33(5):604-9. doi: 10.1016/j.vaccine.2014.12.030. Epub 2014 Dec 29.

    PubMed 25554240
  • Saad CG, Borba EF, Aikawa NE, Silva CA, Pereira RM, Calich AL, Moraes JC, Ribeiro AC, Viana VS, Pasoto SG, Carvalho JF, Franca IL, Guedes LK, Shinjo SK, Sampaio-Barros PD, Caleiro MT, Goncalves CR, Fuller R, Levy-Neto M, Timenetsky Mdo C, Precioso AR, Bonfa E. Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases. Ann Rheum Dis. 2011 Jun;70(6):1068-73. doi: 10.1136/ard.2011.150250.

    PubMed 21540203
  • Aikawa NE, Campos LM, Silva CA, Carvalho JF, Saad CG, Trudes G, Duarte A, Miraglia JL, Timenetsky Mdo C, Viana VS, Franca IL, Bonfa E, Pereira RM. Glucocorticoid: major factor for reduced immunogenicity of 2009 influenza A (H1N1) vaccine in patients with juvenile autoimmune rheumatic disease. J Rheumatol. 2012 Jan;39(1):167-73. doi: 10.3899/jrheum.110721. Epub 2011 Nov 15.

    PubMed 22089462
  • Borba EF, Saad CG, Pasoto SG, Calich AL, Aikawa NE, Ribeiro AC, Moraes JC, Leon EP, Costa LP, Guedes LK, Silva CA, Goncalves CR, Fuller R, Oliveira SA, Ishida MA, Precioso AR, Bonfa E. Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy? Rheumatology (Oxford). 2012 Jun;51(6):1061-9. doi: 10.1093/rheumatology/ker427. Epub 2012 Jan 31.

    PubMed 22298793
  • Korsun N, Angelova S, Trifonova I, Tzotcheva I, Mileva S, Voleva S, Georgieva I, Perenovska P. Predominance of influenza A(H3N2) viruses during the 2016/2017 season in Bulgaria. J Med Microbiol. 2018 Feb;67(2):228-239. doi: 10.1099/jmm.0.000668. Epub 2018 Jan 3.

    PubMed 29297852
  • Chiu SS, Kwan MYW, Feng S, Wong JSC, Leung CW, Chan ELY, Chan KH, Ng TK, To WK, Cowling BJ, Peiris JSM. Influenza Vaccine Effectiveness Against Influenza A(H3N2) Hospitalizations in Children in Hong Kong in a Prolonged Season, 2016/2017. J Infect Dis. 2018 Apr 11;217(9):1365-1371. doi: 10.1093/infdis/jiy027.

    PubMed 29346614
  • Skowronski DM, Chambers C, De Serres G, Dickinson JA, Winter AL, Hickman R, Chan T, Jassem AN, Drews SJ, Charest H, Gubbay JB, Bastien N, Li Y, Krajden M. Early season co-circulation of influenza A(H3N2) and B(Yamagata): interim estimates of 2017/18 vaccine effectiveness, Canada, January 2018. Euro Surveill. 2018 Feb;23(5):18-00035. doi: 10.2807/1560-7917.ES.2018.23.5.18-00035.

    PubMed 29409570
  • Aikawa NE, Borba EF, Balbi VA, Sallum AME, Buscatti IM, Campos LMA, Kozu KT, Garcia CC, Capao ASV, de Proenca ACT, Leon EP, da Silva Duarte AJ, Lopes MH, Silva CA, Bonfa E. Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus. Adv Rheumatol. 2023 Nov 28;63(1):55. doi: 10.1186/s42358-023-00339-7.

    PubMed 38017564
  • Claudino Formiga FF, Silva CA, Pedrosa TDN, Aikawa NE, Pasoto SG, Garcia CC, Capao ASV, Martins VAO, Proenca ACT, Fuller R, Yuki EFN, Vendramini MBG, Rosario DCD, Brandao LMKR, Sartori AMC, Antonangelo L, Bonfa E, Borba EF. Influenza A/Singapore (H3N2) component vaccine in systemic lupus erythematosus: A distinct pattern of immunogenicity. Lupus. 2021 Oct;30(12):1915-1922. doi: 10.1177/09612033211040371. Epub 2021 Aug 28.

    PubMed 34459317

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 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 people with Systemic Lupus and Sjogren's Syndrome, run by University of Sao Paulo General Hospital at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with seroprotection and seroconversion after Influenza vaccine (time frame: 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03540823, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2019.

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