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.
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 18-80 years
In good general health as evidenced by medical history or diagnosed with SLE diagnosed per American College of Rheumatology 1997 revised SLE classification criteria.
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.
Aspartate aminotransferase (AST) >2.5 x upper limit of normal (ULN).
Single group
anifrolumab
DrugThis 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 SLE.
Placebo
Other interventionnon-active substance comprised of 25 mM histidine/histidine-HCl, 50 mM lysine-HCl, 130 mM trehalose, and 0.05% (w/v) polysorbate 80, with a pH of 5.9.
role of anifrolumab
1.Change from Baseline (Week 0) to Week 28 in cardio-ankle vascular index (CAVI). 2. Change from Baseline to Week 28 in pulse wave velocity (PWV) using Sphygmocor. 3. Change from Baseline to Week 28 in vascular inflammation as measured by target to background ratio (TBR) in various aortic territories and total aorta using FDG PET CT scans.
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
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