A Study to Evaluate the Treatment Outcomes of Subcutaneous Anifrolumab in Immunosuppressant-naïve and Biologic-naïve Systemic Lupus Erythematosus

Summary

The purpose of the SUNFLOWER study is to describe clinical outcomes, including DORIS remission, achieved following the initiation of anifrolumab 120 mg SC once weekly (QW) as add-on therapy to an anti-malarial, with or without GC; in patients not in LLDAS at enrolment. Patients will be naïve to any prior conventional immunosuppressant including prior biologic therapy at enrolment. The study will also employ a tapering protocol for a systematic approach to GC tapering, seeking to understand better the proportion of patients in remission who can successfully withdraw chronic GC completely.

Eligibility

Inclusion Criteria:

1. Males or females aged 18 to 70 years of age.
2. Participants who have a diagnosis of SLE confirmed by a rheumatologist.
3. ANA-positive per the Central Lab at screening:

   (a) ANA (b) Anti-dsDNA (c) Anti-Smith (anti-Sm)
4. Must be on the standard therapy regimen: antimalarials with or without OCSs
5. Must have at screening and baseline:

   1. Clinical SLEDAI-2K ≥ 4 points OR
   2. Clinical SLEDAI-2K \< 4 with GC dose ≥ 7.5 mg/day (prednisone equivalent)
6. Should have no evidence of current active infection, (e.g., pneumonia, tuberculosis \[TB\]) or previous TB
7. Should have no evidence of malignancy; and clinically significant abnormalities (unless due to SLE).
8. No medical history or signs or symptoms of active TB prior to or during Screening.
9. Body weight ≥ 40.0 kg
10. Negative pregnancy test for females during screening
11. Normal HPV test result within 2 years prior to Week 0 (Day 1).
12. Willing and able to participate in all required study evaluations and procedures including completion of PROs.
13. Willing to not use any other forms of experimental treatment during the study.

Exclusion Criteria:

1. Subjects with history of, or current diagnosis of, a clinically significant non-SLE related vasculitis syndrome.
2. Subjects with antiphospholipid antibody syndrome on stable anticoagulant therapy at an effective dose (e.g., if on warfarin, an international normalized ratio \[INR\] target 2 to 3 or as appropriate for the clinical situation) are only allowed if this is not the sole or the predominant feature of their SLE.
3. Subjects with a serious thrombotic event (e.g., pulmonary embolism stroke, deep vein thrombosis) or unexplained pregnancy loss within 1 year before the screening visit are excluded.
4. Subjects with a history of catastrophic antiphospholipid syndrome or saddle embolism.
5. Subjects with a history of 3 or more unexplained consecutive pregnancy losses.
6. History or evidence of suicidal ideation within the past 6 months; or any suicidal behavior within the past 12 months or recurrent suicidal behavior in the lifetime of the participant based on an assessment with the Columbia Suicide Severity Rating Scale (C SSRS) at Screening.
7. 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, lupus headache and mononeuritis multiplex, where, protocol-specified standard therapy is insufficient.
8. Active severe SLE-driven renal disease where, protocol-specified standard therapy is insufficient.
9. Current diagnosis of, catastrophic antiphospholipid syndrome (APS).
10. History of recurrent infection requiring hospitalization and IV antibiotics (e.g., 3 or more of the same type of infection over the previous 52 weeks).
11. Known History of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for HIV at Screening.
12. Confirmed positive test for hepatitis B.
13. Any clinical cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection that has not completely resolved within 12 weeks prior to signing the ICF.
14. Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of Week 0 (Day 1).
15. Clinically significant chronic infection (e.g., osteomyelitis, bronchiectasis, etc.) within 8 weeks prior to signing the ICF (chronic nail infections are allowed).
16. Severe HZ or recurrent HZ.
17. Malignancy. History of cancer, apart from:

    (a) Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1).

    (a) Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1).
18. Received any SLE-related therapies other than antimalarials and GCs.
19. History of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy.
20. History of an anaphylactic reaction to human proteins or mAbs.
21. Received any live or attenuated vaccine within 8 weeks prior to signing the ICF.
22. Blood transfusion or receipt of blood products except albumin.
23. Received more than 2 investigational products for the SLE since time of diagnosis.
24. Received any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater.
25. Concurrent enrollment in another clinical study with a study intervention.
26. Subjects with any abnormal lab result as specified in the protocol.
27. Subjects with other autoimmune diseases (e.g., multiple sclerosis, psoriasis, IBD, etc.).
28. Subjects with SLE overlap syndromes such as scleroderma and mixed connective tissue disease.
29. Subject with non-SLE concomitant illness, as determined by medical judgment, who is likely to require additional systemic glucocorticosteroid therapy during the study (e.g., asthma).
30. Any condition would interfere with treatment outcomes of the study intervention or put participant at safety risk.
31. Lactating, breastfeeding, or pregnant females or females who intend to become pregnant or begin breastfeeding anytime from initiation of Screening until 16 weeks following last dose of study intervention.
32. Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to signing the ICF.
33. Current alcohol, drug or chemical abuse, or a history of such abuse within 1 year before Week 0 (Day 1).
34. Major surgery within 8 weeks before signing the ICF or elective major surgery planned during the study period.

Conditions2

Interventions1

Locations21 sites

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