A Study of the Efficacy and Safety of MEDI-546 in Systemic Lupus Erythematosus

An SRI (4) responder defined as a participant who had 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of greater than or equal to (>=) 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of >= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index 'A' organ system score and no more than one new or worsening BILAG-2004 Index 'B' organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 [less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1]. SRI was analyzed by a logistic regression model.

Type I IFN signature in whole blood assessed by using a 4-gene diagnostic test. The blood samples collected were to be used to prospectively identify participants as IFN test-high or test-low. The results of this test were used to stratify participants. An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of >= 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of >= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 [less than 10 mg/day and less or equal to the dose received on Day 1]. SRI was analyzed by a logistic regression model.

An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of >= 4 points; 2) no worsening of disease from baseline as measured by the MDGA (worsening was defined as an increase of >= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 281 through Day 365 (less than 10 mg/day and less or equal to the dose received on Day 1). SRI was analyzed by a logistic regression model.

Participants on OCS >=10 mg/day of prednisone or equivalent at baseline who were able to taper to <= 7.5 mg/day at Day 365 were evaluated.

An adverse event (AE) was any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A serious AE (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly (in offspring of participant). AEs may be treatment emergent (TE) [that is, occurring after initial receipt of investigational product] or non-TE. An AESI is one of scientific and medical concern specific to understanding biologics and requires close monitoring and rapid communication by investigator to sponsor.

Any medically significant change in laboratory evaluations were recorded as Treatment emergent adverse events.

Vital sign parameters are temperature, blood pressure, respiratory rate, heart rate and weight. Vital signs abnormalities were reported as TEAEs.

Any medically significant changes from the screening ECG was recorded as TEAEs. An abnormal ECG findings such as QT prolonged were reported as treatment emergent adverse events.

Anti-drug antibody responses to anifrolumab in serum were evaluated.

The PD positive and negative gene signature was determined by comparing the expression of type I IFN-inducible genes in a 21-gene panel in study participants relative to pooled normal blood collected from healthy participants.

Maximum plasma concentration (Cmax) was defined as the peak plasma level of anifrolumab, derived from plasma concentration -time data.

Accumulation ratio for maximum plasma concentration (Cmax,AR) of anifrolumab after multiple administration at Day 169 and 337 was calculated.

Trough concentration (Ctrough) of anifrolumab at Day 29, 169 and 365 were calculated.

Accumulation ratio for trough concentration (Ctrough,AR) of anifrolumab after multiple administration at Day 169 and 365 was calculated.