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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2026 by AstraZeneca
Sponsor
AstraZeneca
Information Provided by (Responsible Party)
AstraZeneca
Clinicaltrials.gov Identifier
NCT07430306
Other Study ID Numbers:
D3461C00040
First Submitted
February 1, 2026
First Posted
February 23, 2026
Last Update Posted
May 4, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Systemic Lupus Erythematosus
Drug: Anifrolumab

Study Design

Study TypeInterventional
Actual Enrollment245 participants
Design AllocationNon-Randomized
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleMultinational, Interventional, 52-week, Open-label, Single-arm Study to Evaluate the Treatment Outcomes of Anifrolumab 120 mg Subcutaneous Once Weekly in Immunosuppressant-naïve and Biologic-naïve Systemic Lupus Erythematosus (SUNFLOWER)
Study Start DateApril 12, 2026
Actual Primary Completion Date2yrs 8mos from now
Actual Study Completion Date2yrs 8mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Anifrolumab
Participants will receive dose A of anifrolumab on X dosing schedule beginning on Day 1 for a maximum of 52 -week during the study
Drug: Anifrolumab
Patients will receive Anifrolumab subcutaneous

Outcome Measures

Primary Outcome Measures
  1. Attainment of DORIS remission
    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 \[0-3\] \&lt; 0.5, prednisone 5 mg/day or less, and stable antimalarials, ISs, and biologics.
Secondary Outcome Measures
  1. To assess the attainment of low level disease activity
    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 &le; 4 without major organ involvement, no new disease activity, PGA &le; 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 &le; 4 without major organ involvement, no new disease activity, PGA &le; 1 (0 - 3), prednisone 5.0 mg/day or less (this is modified LLDAS to include EULAR 2023 recommendations to lower daily maintenance GC &le; 5.0 mg/day)
  2. Time spent in DORIS remission, LLDAS or LLDAS-5
    Time spent in DORIS remission, LLDAS or LLDAS-5 for participants initiated on anifrolumab will be measured.
  3. Sustaining DORIS remission, LLDAS or LLDAS-5
    The proportion of participants initiated on anifrolumab, sustaining DORIS remission, LLDAS or LLDAS-5 through to Week 52 will be measured.
  4. Sustaining DORIS remission, LLDAS or LLDAS-5
    The proportion of participants initiated on anifrolumab, sustaining DORIS remission, LLDAS or LLDAS-5 for three or more consecutive visits will be measured. Consecutive visits&#039; are defined as three back-to-back completed visits.
  5. Time to attain and sustain DORIS, or LLDAS, or LLDAS-5
    The time to attain and sustain DORIS, or LLDAS, or LLDAS-5 will be analyzed.
  6. Daily GC dose
    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.
  7. Reduction in GC use
    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
  8. Maintenance of reduction in GC dose
    Maintenance of this percent reduction in GC dose through Week 52 will be assessed
  9. Cumulative GC dose
    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.
  10. Attainment of DORIS-0
    Proportion of participants who attain DORIS-0 from baseline over 52 weeks. DORIS-0 is defined as DORIS criteria with prednisone 0 mg daily.
  11. Time to first moderate-to-severe flare
    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.
  12. Change in active skin manifestations
    The change in active skin manifestations of SLE measured by CLASI activity score in participants initiated on anifrolumab will be assessed.
  13. Change in joint activity
    The average change in number of active joints (swollen and tender joints) in participants initiated on anifrolumab compared to baseline will be assessed
  14. Change in QoL and fatigue
    Change in QoL and fatigue in participants initiated on anifrolumab will be assessed using FACIT-F.
  15. Adverse Events
    Safety and tolerability of anifrolumab will be assessed.
  16. Change in QoL and fatigue
    Change in QoL and fatigue in participants initiated on anifrolumab will be assessed using PROMIS Lupus.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsAstraZeneca
Locations
Research Site | Anniston Alabama, United States, 36207Research Site | Phoenix Arizona, United States, 85032Research Site | Fontana California, United States, 92335Research Site | La Palma California, United States, 90623Research Site | Menifee California, United States, 92586Research Site | San Leandro California, United States, 94578Research Site | Temecula California, United States, 92592Research Site | Miami Florida, United States, 33145Research Site | Miami Florida, United States, 33180Research Site | Willowbrook Illinois, United States, 60527Research Site | New Albany Indiana, United States, 47150Research Site | Kansas City Missouri, United States, 64151Research Site | Oklahoma City Oklahoma, United States, 73116Research Site | Memphis Tennessee, United States, 38104Research Site | Memphis Tennessee, United States, 38119Research Site | Austin Texas, United States, 78745Research Site | Baytown Texas, United States, 77521Research Site | Colleyville Texas, United States, 76034Research Site | Edinburg Texas, United States, 78550Research Site | Houston Texas, United States, 77054Research Site | Spokane Washington, United States, 99204Research Site | Calgary Alberta, Canada, T2T 5C7Research Site | Winnipeg Manitoba, Canada, R3A 1M4Research Site | Hamilton Ontario, Canada, L8N 3Z5Research Site | Toronto , Canada, M5T 2S8Research Site | Clermont-Ferrand , France, 63000Research Site | Paris , France, 75012Research Site | Paris , France, 75013Research Site | Vandœuvre-lès-Nancy , France, 54511Research Site | Hamburg , Germany, 22763Research Site | Mainz , Germany, 55131Research Site | München , Germany, 80336Research Site | Brescia , Italy, 25123Research Site | Catania , Italy, 95123Research Site | Ferrara , Italy, 44121Research Site | Florence , Italy, 50141Research Site | Milan , Italy, 20122Research Site | Milan , Italy, 20122Research Site | Padova , Italy, 35128Research Site | Pisa , Italy, 56124Research Site | Roma , Italy, 00161Research Site | Roma , Italy, 00168Research Site | Rozzano , Italy, 20089Research Site | Udine , Italy, 33100Research Site | Culiacán , Mexico, 80000Research Site | Durango , Mexico, 34080Research Site | Guadalajara , Mexico, 44160Research Site | Guadalajara , Mexico, 44650Research Site | Guadalajara , Mexico, 44690Research Site | México , Mexico, 03100Research Site | México , Mexico, 14080Research Site | Bydgoszcz , Poland, 85-065Research Site | Krakow , Poland, 30-688Research Site | Lodz , Poland, 90-368Research Site | Lublin , Poland, 20-607Research Site | Nadarzyn , Poland, 05-830Research Site | Nowa Sól , Poland, 67-100Research Site | Poznan , Poland, 60-693Research Site | Poznan , Poland, 61-397Research Site | Warsaw , Poland, 05-077Research Site | Wroclaw , Poland, 53-673Research Site | Córdoba , Spain, 14004Research Site | Galdakao , Spain, 48960Research Site | Madrid , Spain, 28034Research Site | Madrid , Spain, 28046Research Site | Sabadell , Spain, 08208Research Site | Santander , Spain, 39008Research Site | Valencia , Spain, 46026Research Site | Kaohsiung City , Taiwan, 813414Research Site | Kaohsiung City , Taiwan, 833Research Site | Taichung , Taiwan, 40705Research Site | Tainan , Taiwan, 70403Research Site | Taoyuan , Taiwan, 33305