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INCLUSION CRITERIA:
In order to be eligible to participate in this study, an individual must meet all of the
following criteria:
1.
Provision of signed and dated informed consent form. 2. Stated willingness to comply with all study procedures and availability for the
duration of the study. 3. Male or female, aged 18-80 years. 4. In good general health as evidenced by medical history or diagnosed with SLE diagnosed
per American College of Rheumatology 1997 revised SLE classification criteria.
5. Prednisone < or equal to 10 mg/day for at least 2 weeks before screening and
maintained throughout randomization (day 1)
6. Stable standard of care lupus therapies for at least 4 weeks before screening and
maintained through randomization (day 1)
7. Abnormal cardio-ankle vascular index(CAVI) at screening OR up to 90 days prior to the
screening visit (based on 2 SD above median of healthy controls based on historical
data from our own patient cohorts 8. 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.
9. For females and males of reproductive potential: use of highly effective contraception
from screening and agreement to use such a method during study participation and for an
additional 16 weeks after the end of study medication administration. For the purpose of
this study abstinence will be considered as an effective form of contraception.
10. Subjects must have evidence of vaccination against COVID-19 and Varicella Zoster such
as vaccine records, or detectable antibodies in serum.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation
in this study:
1. 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.
2. Concurrent enrolment in another clinical study with an investigational product. 3. Major surgery within 8 weeks before signing the ICF or elective major surgery planned
during the study period.
4. Any of the following found at Screening:
- - Aspartate aminotransferase (AST) >2.5 X upper limit of normal (ULN).
- - Alanine aminotransferase (ALT) >2.0 X ULN.
- - Total bilirubin >ULN (unless due to Gilbert's syndrome)
- Serum creatinine >2.5 mg/dL (or >181 micromol/L)
- Urine protein/creatinine ratio >2.0 mg/mg (or >226.30 mg/mmol)
- Neutrophil count <1000/microL (or <1.0 X 109/L)
- Platelet count <25000/microL (or <25 X 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.
5. Receipt of any of the following:
1. Azathioprine >200 mg/day. 2. Mycophenolate mofetil > 3 g/day or mycophenolic acid >2.16 g/day. 3. Oral, SC, or intramuscular methotrexate >25 mg/week. 4. Mizoribine >150 mg/day. Leflunomide more than 20 mg and any other
immunosuppressant usage at the discretion of the PI.
6. 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.
7. Prior receipt of anifrolumab.
8. Receipt of any commercially available biologic agent within 5 half-lives prior to
signing of the ICF. 9. 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.
10. 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)
11. Receipt of the following medications during the study period will lead to immediate
discontinuation of investigational product:
- - 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.
- - Any immunoglobulin (Ig) therapy.
- - Intravenous corticosteroids >1 gm methylprednisolone or equivalent.
12. 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.
13. Recent cardiac or stroke event (with in the last year prior to week 0 (day 1))
14. Active SLE disease with SLEDAI 2K >6. 15. 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:
1. That would make the subject unable to fully understand the ICF OR. 2. 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. 16. 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.
17. 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.
18. 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.
19. Confirmed positive test for hepatitis B serology for:
1. Hepatitis B surface antigen (HBsAg), OR. 2. Hepatitis B core antibody (HBcAb)
3. If positive for HBcAb we will check hepatitis B virus (HBV) DNA. If HBV DNA is
detected above the lower limit of quantitation (LLOQ) by at screening subject
will be excluded. 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.
20. Positive test for hepatitis C antibody along with detectable Hepatitis C viral RNA.
21. 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)
22. Any herpes zoster, cytomegalovirus (CMV) or Epstein-Barr virus infection that has not
completely resolved within 12 weeks prior to signing the ICF.
23. Any of the following:
1. Clinically significant chronic infection (i.e., osteomyelitis, bronchiectasis,
etc.) within 8 weeks prior to week 0 (day1) (chronic nail infections are allowed)
2. Any infection requiring hospitalization or treatment with IV antibiotics not
completed at least 4 weeks prior to week 0 (day1)
24. Any infection requiring oral antimicrobials (including antivirals) within 2 weeks
prior to Day 1, except if taking antivirals/antimicrobials prophylactically.
25. History of cancer, apart from:
1. Squamous or basal cell carcinoma of the skin treated with documented success of
curative therapy >=3 months prior to Week 0 (Day 1)
2. Cervical cancer in situ treated with apparent success with curative therapy
(Bullet)1 year prior to Week 0 (Day 1).
26. Pregnancy or lactation or intend to become pregnant anytime from initiation of
Screening until completion of study.
27. Spontaneous or induced abortion, still or live birth, or pregnancy 4 weeks prior to
week 0 (day1)
28. Known allergic reactions to any component of the investigational product formulation
or history of anaphylaxis to any human gamma globulin therapy.
29. Tested positive for COVID-19 infection on the day of screening or up to 21 days prior
to screening.
