The Role of Anifrolumab in Improving Markers of Vascular Risk in Patients With Systemic Lupus Erythematosus (SLE) - IFN-CVD

This is an interventional treatment trial for Systemic Lupus Erythematosus focused on measuring Vascular Inflammation, Interferons, Vascular Function Read More

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• 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.
• Prednisone < or equal to 10 mg/day for at least 2 weeks before screening and maintained throughout randomization (day 1)
• Stable standard of care lupus therapies for at least 4 weeks before screening and maintained through randomization (day 1)
• Abnormal cardio-ankle vascular index at screening (based on 2 SD above median of healthy controls based on historical data from our own patient cohorts)
• Stable medications for diabetes, hypertension and/or statins for at least the previous 3 months. No changes of these medications or immunosuppressive drugs will be allowed during trial.
• For females of reproductive potential: use of highly effective contraception from screening and agreement to use such a method during study participation and for an additional 8 weeks after the end of study medication administration
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

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:

  • Aspartate aminotransferase (AST) >2.5 (SqrRoot) upper limit of normal (ULN).
  • Alanine aminotransferase (ALT) >2.0 (SqrRoot) ULN.
  • Total bilirubin >ULN (unless due to Gilbert's syndrome)
  • Serum creatinine >2.5 mg/dL (or >181 micromole/L)
  • Urine protein/creatinine ratio >2.0 mg/mg (or >226.30 mg/mmol)
  • Neutrophil count <1000/microliter (or <1.0 (SqrRoot) 109/L)
  • Platelet count <25000/microliter (or <25 (SqrRoot) 109/L)
  • Hemoglobin <8 g/dL (or <80 g/L), or <7 g/dL (or <70 g/L) if related to subject's SLE such as in active hemolytic anemia
  • Glycosylated hemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic subjects only)
  • Positive SARS-CoV-2 (PCR)

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: (a) Azathioprine >200 mg/day (b) Mycophenolate mofetil > 3 g/day or mycophenolic acid >2.16 g/day (c) Oral, SC, or intramuscular methotrexate >25 mg/week (d) Mizoribine >150 mg/day.
• 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.
• Prior receipt of anifrolumab
• 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 ocrelizumab, ofatumumab, atacicept, obintusumab, 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.

An absolute B cell count less than the lower limit of normal OR lower than the subject s baseline value prior to receipt of B cell-depleting therapy (whichever is lower):): after >=26 weeks prior to the signing of the consent for all B-cell therapy (except atacicept) or 40 weeks 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:

  • Cyclophosphamide
  • IFN therapy (alpha 2a and 2b, beta 1a and 1b, and pegylated IFNs alpha 2a and 2b)
  • Investigational agents
  • Biologic immunomodulators (including, but not limited to, belimumab, abatacept, or rituximab)
  • Live or attenuated vaccines
  • Plasmapheresis
  • BCG vaccine
  • Any immunoglobulin (Ig) therapy
  • Intravenous corticosteroids >1 gm methylprednisolone or equivalent
• 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
• 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: (a) That would make the subject unable to fully understand the ICF OR (b) Where, in the opinion of the Principal Investigator (PI), protocol specified 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
• 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: (a) Hepatitis B surface antigen (HBsAg), OR (b) Hepatitis B core antibody (HBcAb) AND hepatitis B virus (HBV) DNA detected above the lower limit of quantitation (LLOQ) by reflex testing by the central laboratory at screening Note: Subjects who are HBcAb positive at screening will be tested every 3 months 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: (a) Clinically significant chronic infection (ie, osteomyelitis, bronchiectasis, etc) within 8 weeks prior to week 0 (day1) (chronic nail infections are allowed) (b) Any infection requiring hospitalization or treatment with IV antibiotics not completed at least 4 weeks prior to week 0 (day1)
• 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: (a) Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy greater than or equal to 3 months prior to Week 0 (Day 1) (b) Cervical cancer in situ treated with apparent success with curative therapy greater than or equal to 1 year prior to Week 0 (Day 1).
• 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 less than or equal 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