Pilot Study to Assess Flares Following Inactivated Influenza Vaccine in Children With Systemic Lupus Erythematosus (SLE)

This is an open label, pilot, observational, prospective study of the safety of inactivated
influenza vaccine (IIV) in children with systemic lupus erythematosus (SLE) to be conducted
during the 2013-2014 influenza season.

Annual receipt of IIV is recommended for persons with SLE and is considered a standard of
care medical practice. The study will test conventional and novel biomarkers to assess
disease flare and vaccine response and will also collect self-reported signs/symptoms in
reactogenicity diaries during the 14 days after vaccination.

Little is known about the immune responses to influenza and other vaccines in children and
adolescents with autoimmune conditions, both in terms of immunogenicity as well as the
potential for triggering or worsening of immune/autoimmune pathways. Patients with SLE often
must take two or more immunosuppressive medications to control their illness. Thus, it is
critically important to study vaccine safety and immunogenicity within the pediatric SLE
population rather than extrapolate the limited data available from adult clinical studies.
Newly diagnosed, untreated patients will be too sick to include in this study. After that,
patients are on some immunosuppressive regimen for an extended period of time.

This project will inform the process for a subsequent larger multi-center study to assess
IIV safety utilizing an established clinical research network in pediatric rheumatology,
such as the Childhood Arthritis and Rheumatology Research Alliance (CARRA) or other venue.

The pilot study will enroll 30 children with mild to moderate SLE as defined by a Systemic
Lupus Erythematosus Disease Activity Index (SLEDAI) of <6. A SLEDAI score is an SLE Disease
Activity Index which consists of 24 items made up of both clinical data and laboratory
results. This score is assessed each time that a patient with SLE is seen in the clinic. It
is anticipated that the subjects would be enrolled over 2 to 3 months prior to the influenza
season, so as to immunize the SLE patients with IIV before they would be exposed to the
circulating wild-type influenza virus. Patients will be followed for 3 months.

Thirty patients receiving one of two different treatment regimens that are standard-of-care
regimes, "Prednisone + Hydroxychloroquine" or Prednisone+ Hydroxychloroquine + Mycophenolate
Mofetil (MMF), will be observed. All subjects will receive US-licensed influenza vaccines as
part of standard medical practice.

These two regimens were chosen because they represent customary care immunosuppressant
medication regimens for persons with SLE. In addition, MMF in the second treatment arm has
an inhibitory effect on plasma cell development, therefore allowing us to explore whether
patients receiving this drug will have diminished antibody responses in response to
vaccination.

Fifteen patients will already be receiving Prednisone + Hydroxychloroquine and 15 patients
will already be receiving Prednisone+ Hydroxychloroquine + Mycophenolate Mofetil (MMF) as
their routine care

Inclusion Criteria:

INCLUSION CRITERIA:

Subjects who meet the following criteria will be allowed to participate in the study:

1. Complete immunization history must be available at time of enrollment

2. Patients will be aged 8-18 years at time of enrollment

3. Patient will have stable disease activity (no changes in SLEDAI >2 points) during the
3 months preceding enrollment.

4. Patients can be enrolled as soon as the seasonal IIV is available and prior to the
onset of influenza activity in the community. Generally this will be between
September 2013-January2014. If feasible, enrollment will end in December 2013, which
is usually before influenza circulates widely in the community.

Exclusion Criteria:

Subjects who meet the following criteria will not be allowed to participate in the study:

1. Females who are known to be pregnant or breastfeeding

2. Moderate to high SLE disease activity at enrollment (SLEDAI >6)

3. Oral temp ≥100F (≥37.8) within 72 hours prior to vaccination

4. History of allergy to egg or egg products or history of allergic reaction to previous
influenza vaccination or vaccine constituent

5. History of Guillain-Barré syndrome after previous immunizations

6. Unstable SLE disease activity during 3 months prior to enrollment (change in SLEDAI
score >2)

7. Requirement for high-dose IV Solumedrol and/or Cytoxan pulse therapy during 6 months
prior to study

8. Any condition that study site investigator deems would put patient at unacceptable
risk of injury or render patient unable to meet requirements of the protocol.

9. Received pre-medication with analgesic or antipyretic agents in the 6 hours prior to
first vaccination, or planned medication with analgesic or antipyretic in the week
following first vaccination. This criterion should not preclude subjects receiving
such medication if the need arises. However, pre-medication is to be discouraged.

10. Patient has received other inactivated vaccines within 14 days prior to
administration of IIV.

11. Patient is scheduled to receive another routinely administered inactivated vaccine
within 14 days after IIV.

12. Patient is currently participating in a study that involves and experimental agent
(vaccine, drug, biologic, device, blood product, or medication), or expects to
receive another experimental agent during participation in this study