Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

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 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 analysis threshold.

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.

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.

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.

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.

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.

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.

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).

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).

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).

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.

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).

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).

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

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.