Trial Outcomes & Findings for Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus (NCT NCT02446912)

Last Updated: 2023-01-12

Results Overview

SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) No new organ systems affected, defined by 1 or more British Isles Lupus Assessment Group (BILAG-2004) A or 2 or more BILAG-2004 B items No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

460 participants

Primary outcome timeframe

Week 52

Results posted on

2023-01-12

Participant Flow

Participants took part in the trial at 123 sites in 18 countries worldwide.

Participant milestones

Participant milestones
Measure	Anifrolumab 150 mg Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Overall Study STARTED	93	180	184
Overall Study Participants Who Completed Week 52	80	153	157
Overall Study COMPLETED	75	145	149
Overall Study NOT COMPLETED	18	35	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Anifrolumab 150 mg Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Overall Study Adverse Event	3	13	5
Overall Study Condition under investigation worsened	0	1	1
Overall Study Study-specific withdrawal criteria	1	0	0
Overall Study Lack of Efficacy	1	4	7
Overall Study Lost to Follow-up	0	0	2
Overall Study Severe non-compliance to protocol	1	0	1
Overall Study Withdrawal by Subject	10	15	15
Overall Study Miscellaneous	2	2	4

Baseline Characteristics

Full analysis set - all randomized participants who received at least one dose of investigational product.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Week 52

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules)	35 Participants	65 Participants	74 Participants

SECONDARY outcome

Timeframe: Week 52

Population: All participants who received investigational product with non-missing baseline measurements, and high IFN test results.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=76 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=148 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=151 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Original Analysis With Restricted Medication Rules)	30 Participants	53 Participants	59 Participants

SECONDARY outcome

Timeframe: Week 52

Population: All participants who received investigational product, who had a baseline OCS ≥10 mg/day, and had non-missing baseline measurements.

Maintained OCS reduction was defined by meeting all the following criteria: Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=48 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=103 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=102 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of ≤7.5 mg/Day in the Sub-group of Participants With Baseline OCS ≥10 mg/Day (Original Analysis With Restricted Medication Rules)	17 Participants	42 Participants	33 Participants

SECONDARY outcome

Timeframe: Week 12

Population: All participants who received investigational product, had a baseline CLASI Activity Score ≥10, and had non-missing baseline measurements.

50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score compared to baseline was defined by meeting all of the following criteria: Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold before assessment.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=30 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=58 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=54 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants With a ≥50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score ≥10 (Original Analysis With Restricted Medication Rules)	15 Participants	24 Participants	14 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the pre-specified threshold.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 (SRI[4]) at Week 24 (Original Analysis With Restricted Medication Rules)	34 Participants	74 Participants	75 Participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Full analysis set - all randomized participants who received investigational product with non-missing baseline measurements.

A flare was defined as either 1 or more new British Isle Lupus Assessment Group (BILAG-2004) A or 2 or more new BILAG-2004 B items compared to the previous visit. The occurrence of a new flare was checked for each available visit versus the previous available visit up to Week 52. If no new flares occurred, the number of flares was set to 0. Otherwise all flares were counted leading to the maximum number of flares of 13. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25 (1 year). The flare exposure time is the time up to Week 52 (date of BILAG-2004 assessment at Week 52) or up to the date of last available BILAG-2004 assessment.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Annualized Flare Rate	0.62 Annualized flare rate ratio	0.60 Annualized flare rate ratio	0.72 Annualized flare rate ratio

SECONDARY outcome

Timeframe: Week 52

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Original Analysis With Restricted Medication Rules)	27 Participants	67 Participants	49 Participants

SECONDARY outcome

Timeframe: Baseline to End of Trial (Maximum of 60 weeks)

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. AEs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE). The reported value is inclusive of serious and non-serious AEs.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Reporting One or More Adverse Events (AE)	80 Participants	161 Participants	145 Participants

SECONDARY outcome

Timeframe: Baseline to End of Trial (Maximum of 60 weeks)

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

An AESI is an AE of scientific and medical concern specific to understanding biologics and requires close monitoring and rapid communication by the Investigator to the Sponsor/Sponsor's delegate. An AESI may be serious or nonserious. The events of interest are serious infections, including non opportunistic serious infections, opportunistic infections, anaphylaxis, malignancy, herpes zoster, TB (including latent TB), influenza, vasculitis (non-SLE), and MACE (including stroke, MI, or cardiovascular death). AEs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Reporting One or More Adverse Events of Special Interest (AESI)	11 Participants	23 Participants	18 Participants

SECONDARY outcome

Timeframe: Baseline to End of Trial (Maximum of 60 weeks)

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

Vital signs included oral temperature, blood pressure (BP), pulse rate, and respiratory rate. Vital signs were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants With Markedly Abnormal Vital Signs	14 Participants	36 Participants	46 Participants

SECONDARY outcome

Timeframe: Baseline to End of Trial (Maximum of 60 weeks)

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

Physical examinations included height and weight. Participants were weighed at each study visit and any medically significant changes were reported. Physical examination values were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants With Markedly Abnormal Physical Examinations	3 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

ECGs documented the date, time, heart rate, QRS duration, PR interval, RR interval, QT, and corrected QT interval, which were calculated using the Fridericia formula. The investigator judged the overall interpretation as normal or abnormal, and if abnormal it was decided as to whether or not the abnormality was clinically significant or not clinically significant.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Scores	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to End of Trial (Maximum of 60 weeks)

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

The modified SELENA flare index was completed by the Investigator or delegated/qualified physician. Assessment of flares were scored in comparison to the participant's previous visit and should only include findings which, in the opinion of the Investigator, are due to systemic lupus erythematosus (SLE) disease activity within that timeframe. Flare was defined as any 1 criterion present in either the Mild/Moderate Flare or Severe Flare categories. Number of flares were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants With Mild To Moderate Lupus Flare Evaluated by Modified Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare Index	38 Participants	58 Participants	67 Participants

SECONDARY outcome

Timeframe: Baseline to End of Trial (Maximum of 60 weeks)

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

Laboratory tests were collected at central clinical laboratories and included hematology, serum chemistry and urinalysis tests. Laboratory values were collected throughout the duration of the study, from baseline until end of follow-up (a maximum of 12 weeks post last dose \[Week 48\]), or until Week 52 for participants who enrolled onto the long term extension (LTE).

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants With Markedly Abnormal Laboratory Tests	44 Participants	71 Participants	87 Participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Number of participants with suicidal ideation or behavior was defined as the number of participants who answered "yes" at any time during the treatment period (Baseline to Week 52) to one of the 10 categories: Category 1: Wish to be dead Category 2: Non-specific active suicidal thoughts Category 3: Active suicidal ideation with any methods (not plan) without intent to act Category 4: Active suicidal ideation with some intent to act, without specific plan Category 5: Active suicidal ideation with specific plan and intent Category 6: Preparatory acts or behavior Category 7: Aborted attempt Category 8: Interrupted attempt Category 9: Actual attempt (non-fatal) Category 10: Completed suicide

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants With Suicidal Ideation or Behaviour Assessed Via the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal ideation	1 Participants	2 Participants	2 Participants
Number of Participants With Suicidal Ideation or Behaviour Assessed Via the Columbia Suicide Severity Rating Scale (C-SSRS) Suicidal behaviour	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All participants who received study drug with non-missing baseline and week 52 measurements.

PHQ-8 is a 8-item self-report scale, all items are rated on a score of 0-3, for a total range of 0-24. PHQ-8 assesses symptoms of depression over the previous 2 weeks. Higher scores indicate more depressive symptoms. A negative change from baseline score indicates improvement in symptoms.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=71 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=130 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=138 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Change From Baseline in Personal Health Questionnaire Depression Scale-8 (PHQ-8) Score	-2.1 Score on a Scale Standard Deviation 4.43	-2.7 Score on a Scale Standard Deviation 5.58	-1.7 Score on a Scale Standard Deviation 5.40

POST_HOC outcome

Timeframe: Week 52

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected, defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items No worsening from baseline in lupus disease activity. Worsening defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc allowed threshold. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medications confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Post-Hoc Analysis With Revised Restricted Medication Rules)	45 Participants	84 Participants	79 Participants

POST_HOC outcome

Timeframe: Week 52

Population: All participants who received investigational product with non-missing baseline measurements, and high IFN test results.

SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the SLEDAI-2K No new organ systems affected, defined by 1 or more BILAG-2004 A or 2 or more BILAG-2004 B items No worsening from baseline in lupus disease activity. Worsening defined as an increase of ≥0.30 points on a 3-point PGA VAS No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medications confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=76 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=148 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=151 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Achieved an Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Post-Hoc Analysis With Revised Restricted Medication Rules)	40 Participants	71 Participants	63 Participants

POST_HOC outcome

Timeframe: Week 52

Population: All participants who received investigational product, who had a baseline OCS ≥10 mg/day, and had non-missing baseline measurements.

Maintained OCS reduction was defined by meeting all of the following criteria: Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medication confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=48 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=103 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=102 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of ≤7.5 mg/Day in the Sub-group of Participants With Baseline OCS ≥10 mg/Day (Post-Hoc Analysis With Revised Restricted Medication Rules)	24 Participants	50 Participants	33 Participants

POST_HOC outcome

Timeframe: Week 12

Population: All participants who received investigational product, had a baseline CLASI Activity Score ≥10, and had non-missing baseline measurements.

50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score compared to baseline was defined by meeting all the following criteria: Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold before assessment. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medication confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=30 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=58 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=54 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants With a ≥50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score ≥10 (Post-Hoc Analysis With Revised Restricted Medication Rules)	16 Participants	25 Participants	14 Participants

POST_HOC outcome

Timeframe: Week 24

Population: Full analysis set - all randomized participants who received at least one dose of investigational product.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 (SRI[4]) at Week 24 (Post-Hoc Analysis With Revised Restricted Medication Rules)	40 Participants	83 Participants	79 Participants

POST_HOC outcome

Timeframe: Week 52

Population: Full analysis set - all randomized participants who received at least one dose of investigation product.

A BICLA responder was achieved if all of the following criteria was met: All criteria related to SRI(4) (please see primary endpoint) plus: Reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by 1 or more BILAG-2004 A or 1 or more new BILAG-2004 B item No discontinuation of investigational product and no use of restricted medications beyond the revised post-hoc analysis threshold before assessment. Revised rules were designed to be more clinically appropriate, capture intent of protocol, minimize the risk of restricted medications confounding efficacy, and to allow appropriate quantification and interpretation of the relevant endpoints.

Outcome measures

Outcome measures
Measure	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)
Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Post-Hoc Analysis With Revised Restricted Medication Rules)	35 Participants	83 Participants	54 Participants

Adverse Events

Anifrolumab 150 mg

Serious events: 10 serious events

Other events: 78 other events

Deaths: 0 deaths

Anifrolumab 300 mg

Serious events: 27 serious events

Other events: 157 other events

Deaths: 1 deaths

Placebo

Serious events: 35 serious events

Other events: 141 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Leader

AstraZeneca AB

Phone: +46317761000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Anifrolumab 300 mg n=180 Participants Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Anifrolumab 150 mg n=93 Participants Anifrolumab (150 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Placebo n=184 Participants Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses)	Total n=457 Participants Total of all reporting groups
Age, Continuous	42.0 Years STANDARD_DEVIATION 11.99 • n=7 Participants	40.8 Years STANDARD_DEVIATION 12.05 • n=5 Participants	41.0 Years STANDARD_DEVIATION 12.30 • n=5 Participants	41.3 Years STANDARD_DEVIATION 12.11 • n=4 Participants
Age, Customized < 18	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized ≥ 18 to < 65	169 Participants n=7 Participants	90 Participants n=5 Participants	178 Participants n=5 Participants	437 Participants n=4 Participants
Age, Customized ≥ 65	11 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=5 Participants	20 Participants n=4 Participants
Sex: Female, Male Female	165 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	86 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	171 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	422 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Sex: Female, Male Male	15 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	7 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	13 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	35 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	20 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	35 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	87 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Ethnicity (NIH/OMB) Not Hispanic or Latino	148 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	73 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	149 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	370 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	1 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	1 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) Asian	11 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	8 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	5 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	24 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) Black or African American	29 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	14 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	23 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	66 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) White	125 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	64 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	137 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	326 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) More than one race	0 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	0 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Race (NIH/OMB) Unknown or Not Reported	15 Participants n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	7 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	18 Participants n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	40 Participants n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Height	162.99 cm STANDARD_DEVIATION 7.829 • n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	164.02 cm STANDARD_DEVIATION 8.208 • n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	163.10 cm STANDARD_DEVIATION 8.030 • n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	163.24 cm STANDARD_DEVIATION 7.980 • n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Weight	75.36 kg STANDARD_DEVIATION 20.343 • n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	73.57 kg STANDARD_DEVIATION 19.469 • n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	74.69 kg STANDARD_DEVIATION 19.332 • n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	74.72 kg STANDARD_DEVIATION 19.731 • n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.
Body Mass Index (BMI)	28.25 kg/m2 STANDARD_DEVIATION 6.899 • n=7 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	27.31 kg/m2 STANDARD_DEVIATION 6.81 • n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	28.09 kg/m2 STANDARD_DEVIATION 7.145 • n=5 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.	28.00 kg/m2 STANDARD_DEVIATION 6.976 • n=4 Participants • Full analysis set - all randomized participants who received at least one dose of investigational product.