Systemic Lupus Erythematosus
Conditions
Keywords
Lupus, Immunosuppressant, Glucocorticoid, Anifrolumab, Remission
Brief 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.
Detailed description
In this study, approximately 275 participants will be enrolled and the study duration will be up to approximately 69 weeks, including: A Screening Period lasting up to 35 days and A 52-week treatment period. Also, participants not continuing treatment with any preparation of anifrolumab after Week 52 will have additional safety follow up 12 weeks after last dose of anifrolumab. Anifrolumab will be administered SC via an aPFS during the 52-week Study. The study population will comprise participants taking antimalarial with or without GCs (there is a recruitment cap of 50% of patients not on GC at baseline) who are IS-naïve and biologic-naïve and are not meeting LLDAS criteria, described by the following cohorts: * Clinical SLEDAI 2K ≥4 points regardless of GC dose and disease duration. * Clinical SLEDAI-2K \< 4 with GC ≥ 7.5 mg/day for \> 5 weeks. After receiving the first dose of anifrolumab (week 0), the participant is allowed to increase the GC dose up until week 4, based on the investigator's recommendation. Between week 5 and week 40, participants taking \>5 mg/day GC dose at study entry will attempt a protocolized taper to 5 mg/day over 12 weeks. Participants achieving DORIS remission for 2 consecutive visits will attempt complete withdrawal of GC following a 12-week tapering regimen. Starting week 41 until the end of the study (week 52), there will be no further reduction of GC dose.
Interventions
DRUGAnifrolumab
Patients will receive Anifrolumab subcutaneous
Sponsors
AstraZeneca
ICON plc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multinational, Interventional, 52-week, Open-label, Single-arm Study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Attainment of DORIS remission | At Week 52 | Proportion of participants who are in DORIS remission at Week 52 will be assessed. DORIS remission is defined as Clinical SLEDAI-2K (sum of all SLEDAI-2K items except for increased deoxyribonucleic acid \[DNA\] binding and low complement) = 0; PGA \[0-3\] \< 0.5, prednisone 5 mg/day or less, and stable antimalarials, ISs, and biologics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of reduction in GC dose | During 52 Week | Maintenance of this percent reduction in GC dose through Week 52 will be assessed |
| Cumulative GC dose | Week 0 to Week 52 | The cumulative GC dose from Week 0 to Week 52 in participants initiated on anifrolumab alongside a systematic approach to GC tapering will be assessed. |
| Attainment of DORIS-0 | From baseline over 52 Weeks | Proportion of participants who attain DORIS-0 from baseline over 52 weeks. DORIS-0 is defined as DORIS criteria with prednisone 0 mg daily. |
| Time to first moderate-to-severe flare | Through Week 52 | Time to first moderate-to-severe flare through to Week 52 assessed based on MFI. Moderate-to-severe flare is defined as any one criterion present in the moderate or severe flare categories within the MFI will be assessed. |
| Change in active skin manifestations | At Week 4, Week 16, and Week 52 | The change in active skin manifestations of SLE measured by CLASI activity score in participants initiated on anifrolumab will be assessed. |
| Change in joint activity | At Week 28 and 52 | The average change in number of active joints (swollen and tender joints) in participants initiated on anifrolumab compared to baseline will be assessed |
| Change in QoL and fatigue | At 52 Week | Change in QoL and fatigue in participants initiated on anifrolumab will be assessed using FACIT-F. |
| Adverse Events | Up to 52 Weeks | Safety and tolerability of anifrolumab will be assessed. |
| Time to attain and sustain DORIS, or LLDAS, or LLDAS-5 | Through Week 52 | The time to attain and sustain DORIS, or LLDAS, or LLDAS-5 will be analyzed. |
| Daily GC dose | At Week 40 and Week 52 | The daily GC dose at Week 40 and 52 in participants initiated on anifrolumab alongside a systematic approach to GC tapering and to assess the maintenance of this GC reduction through Week 52 will be assessed. |
| To assess the attainment of low level disease activity | At Week 28 and 52 | Proportion of participants who are in LLDAS, or LLDAS-5 at Week 28 and 52 will be assessed. Low level disease activity as measured by LLDAS and LLDAS 5 * LLDAS criteria: SLEDAI 2K ≤ 4 without major organ involvement, no new disease activity, PGA ≤ 1 (0 - 3), prednisone 7.5 mg/day or less, and permitted use of the following medications: antimalarials, standard maintenance doses of ISs including biologics * LLDAS-5 criteria: SLEDAI-2K ≤ 4 without major organ involvement, no new disease activity, PGA ≤ 1 (0 - 3), prednisone 5.0 mg/day or less (this is modified LLDAS to include EULAR 2023 recommendations to lower daily maintenance GC ≤ 5.0 mg/day) |
| Time spent in DORIS remission, LLDAS or LLDAS-5 | At Week 52 | Time spent in DORIS remission, LLDAS or LLDAS-5 for participants initiated on anifrolumab will be measured. |
| Reduction in GC use | From Week 4 to Week 40 | The reduction in GC use from Week 4 to Week 40 in participants initiated on anifrolumab alongside a systematic approach to GC tapering will be assessed |
| Sustaining DORIS remission, LLDAS or LLDAS-5 | All subsequent visits including 52 Week | The proportion of participants initiated on anifrolumab, sustaining DORIS remission, LLDAS or LLDAS-5 through to Week 52 will be measured. |
Countries
Canada, France, Germany, Italy, Mexico, Poland, Spain, Taiwan, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed