The purpose of this study is to evaluate the efficacy and safety of MEDI-546 compared to placebo in subjects with chronic, moderately-to-severely active systemic lupus erythematosus (SLE) with an inadequate response to standard of care treatment for SLE.
This is a Phase 2, multinational, multicenter, randomized, double-blind, placebo controlled, parallel-group study to evaluate the efficacy and safety of 2 intravenous (IV) treatment regimens in adult participants with chronic, moderately-to-severely active SLE with an inadequate response to SOC SLE. The investigational product (anifrolumab or placebo) will be administered as a fixed dose every 4 weeks (28 days) for a total of 13 doses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
626
Participants will receive 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants will receive 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants will receive placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169
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.
Time frame: Day 169
Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169
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.
Time frame: Day 169
Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365
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Research Site
Birmingham, Alabama, United States
Research Site
La Jolla, California, United States
Research Site
La Palma, California, United States
Research Site
Long Beach, California, United States
Research Site
Los Angeles, California, United States
Research Site
Palm Desert, California, United States
Research Site
San Leandro, California, United States
Research Site
Upland, California, United States
Research Site
Miami, Florida, United States
Research Site
Ocala, Florida, United States
...and 69 more locations
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.
Time frame: Day 365
Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/Day of Prednisone or Equivalent at Baseline Who Were Able to Taper to Less Than or Equal to (<=) 7.5 mg/Day at Day 365
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.
Time frame: Day 365
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)
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.
Time frame: Day 1 (Baseline) to Day 422 (End of Study)
Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events
Any medically significant change in laboratory evaluations were recorded as Treatment emergent adverse events.
Time frame: Day 1 (Baseline) to Day 422 (End of Study)
Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Vital sign parameters are temperature, blood pressure, respiratory rate, heart rate and weight. Vital signs abnormalities were reported as TEAEs.
Time frame: Day 1 (Baseline) to Day 422 (End of Study)
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (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.
Time frame: Day 1 (Baseline) to Day 422 (End of Study)
Percentage of SLE Participants With Positive Anti-drug Antibody (ADA)
Anti-drug antibody responses to anifrolumab in serum were evaluated.
Time frame: Days 1, 85, 141, 169, 253, 337 (Treatment Phase), 365, 396, and 422 (Follow-up Period)
Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature
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.
Time frame: Days 29, 85, 141, 169, 253, 337 (treatment phase), on Days 365, 396, and 422 (follow up period)
Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337
Maximum plasma concentration (Cmax) was defined as the peak plasma level of anifrolumab, derived from plasma concentration -time data.
Time frame: Pre-infusion and 15 minutes post-infusion on Day 1, 169 and 337
Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab
Accumulation ratio for maximum plasma concentration (Cmax,AR) of anifrolumab after multiple administration at Day 169 and 337 was calculated.
Time frame: Pre-infusion and 15 minutes post-infusion on Day 169 and 337
Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365
Trough concentration (Ctrough) of anifrolumab at Day 29, 169 and 365 were calculated.
Time frame: Pre-infusion and 15 minutes post-infusion on Day 29, 169 and 365
Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365
Accumulation ratio for trough concentration (Ctrough,AR) of anifrolumab after multiple administration at Day 169 and 365 was calculated.
Time frame: Pre-infusion and 15 minutes post-infusion on Day 169 and 365