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About
Background:
People with systemic lupus erythematosus (SLE) are at risk of developing complications in their blood vessels. This can increase the risk of heart attacks or stroke. No medications have been effective at reducing this risk in people with lupus.
Objective:
To test whether a drug (anifrolumab) can improve blood vessel function and reduce blood vessel inflammation in people with SLE.
Eligibility:
People aged 18 to 80 years with SLE.
Design:
Participants will undergo screening. They will have a physical exam. They will have blood and urine tests. They will have a test of their heart function and a chest X-ray. They will answer questions about their SLE symptoms.
Participants will visit the clinic 9 times in 8 months. After screening, visits will be 4 weeks apart. Each visit may take up to 4 hours.
Participants will receive infusions from a tube attached to a needle inserted into a vein in the arm (IV). Some will receive anifrolumab. Others will receive a placebo treatment. They will not know which one they are getting.
At some visits they will have additional tests:
CAVI (cardio-ankle vascular index) tests blood vessel function. Participants will lie still for 20 minutes. Small electrodes will be placed on both wrists with stickers. A microphone will be placed on their chest. Blood pressure cuffs will be wrapped around their ankles and arms.
FDG-PET/CT is an imaging procedure. Participants will receive a substance through an IV line. They will lie on a table for 110 minutes while a machine captures images of their body.
Full description
Study Description:
This is a double blind placebo-controlled study to characterize whether blocking type I IFN receptor signaling with anifrolumab will lead to improvements in vascular function, decreases in vascular inflammation and modulation of biomarkers of vascular risk in patients with systemic lupus erythematosus (SLE).
Objectives:
Primary Objective: To assess the role of anifrolumab in modulating vascular function and vascular inflammation in SLE patients with mild to moderate disease activity as determined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K<= 6.
Secondary Objective: To assess the role of anifrolumab in modulating biomarkers of cardiovascular risk in SLE patients with mild to moderate disease activity as determined by SLEDAI 2K<= 6. Assess safety and tolerability of short-term use of anifrolumab
Endpoints:
Primary Endpoint(s):
Secondary Endpoints:
Changes over time in biomarkers of cardiovascular risk/immune dysregulation and metabolic dysfunction previously described in SLE. These biomarkers include but not limited to lipoprotein profiles and high-density lipoprotein cholesterol efflux capacity, immune cell types, endothelial progenitor cells, circulating neutrophil extracellular traps, serum cytokines, acute phase reactants, insulin resistance, transcriptomic analysis of peripheral immune cells.
Tertiary: Safety, as assessed by severity and incidence of adverse events and the change over time from baseline in laboratory variables.
Enrollment
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Inclusion and exclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this
study:
Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
Concurrent enrolment in another clinical study with an investigational product
Major surgery within 8 weeks before signing the ICF or elective major surgery planned during the study period.
Any of the following found at Screening:
Note: Abnormal screening test(s) which exclude the patient may be repeated once within 4 weeks of the Screening Visit. If the repeat test(s) does not meet the above criteria, then the patient may be included in the study and will not be considered a screen failure.
Receipt of any of the following:
Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to week 0 (day 1), whichever is greater.
Receipt of any commercially available biologic agent within 5 half-lives prior to signing of the ICF
Receipt of B cell depleting therapy (including but not limited to belimumab, ocrelizumab, ofatumumab, atacicept, Obinutuzumab, or rituximab), <26 weeks prior to the signing of the consent for all B-cell depleting therapy or <40 weeks prior to the signing of the ICF for atacicept.
Receipt of any of the following: (a) Intra-articular, intramuscular or IV corticosteroids within 4 weeks prior to Day 1 (b) Any live or attenuated vaccine within 8 weeks prior to signing the ICF (administration of killed vaccines is acceptable)
Receipt of the following medications during the study period will lead to immediate discontinuation of investigational product:
History or evidence of suicidal ideation within the past 6 months; or any suicidal behavior within the past 12 months based on screening or at baseline.
Recent cardiac or stroke event (with in the last year prior to week 0 (day 1))
Active SLE disease with SLEDAI 2K >6 at the time of screening.
Active severe or unstable neuropsychiatric SLE including, but not limited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; and mononeuritis multiplex:
Active severe SLE-driven renal disease where, in the opinion of the PI, protocol specified standard of care (SOC) is insufficient and utilization of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated.
History of or current diagnosis of catastrophic or severe anti-phospholipid syndrome within 1 year prior to signing the ICF. Antiphospholipid syndrome adequately controlled by anticoagulant therapy for at least 3 months is acceptable.
Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation.
Confirmed positive test for hepatitis B serology for:
Note: Subjects who are only HBcAb positive at screening will be tested every month for HBV DNA. To remain eligible for the study, the subject s HBV DNA levels must remain below the LLOQ as per the central laboratory.
Positive test for hepatitis C antibody along with detectable Hepatitis C viral RNA.
Any severe herpes infection at any time prior to Week 0 (Day 1), including, but not limited to, disseminated herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years) or ophthalmic herpes (ever)
Any herpes zoster, cytomegalovirus (CMV) or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF.
Any of the following:
Any infection requiring oral antimicrobials (including antivirals) within 2 weeks prior to Day 1, except if taking antivirals/antimicrobials prophylactically.
History of cancer, apart from:
Pregnancy or lactation or intend to become pregnant anytime from initiation of Screening until completion of study.
Spontaneous or induced abortion, still or live birth, or pregnancy <= to 4 weeks prior to week 0 (day1)
Known allergic reactions to any component of the investigational product formulation or history of anaphylaxis to any human gamma globulin therapy.
Tested positive for COVID-19 infection on the day of screening or up to 21 days prior to screening.
Primary purpose
Allocation
Interventional model
Masking
45 participants in 2 patient groups, including a placebo group
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Central trial contact
Lubna K Hooda, R.N.; Mariana J Kaplan, M.D.
Data sourced from clinicaltrials.gov
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