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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01438489
Recruitment Status : Completed
First Posted : September 22, 2011
Results First Posted : August 15, 2016
Last Update Posted : October 7, 2016
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Systemic Lupus Erythematosus
Interventions Biological: Anifrolumab 300 mg
Biological: Anifrolumab 1000 mg
Other: Placebo
Enrollment 626
Recruitment Details  
Pre-assignment Details A total of 626 participants were screened out of which 319 participants did not meet eligibility criteria and were considered screen failures, and 307 participants were randomized into the study.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks. Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks. Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Period Title: Overall Study
Started 103 100 104
Completed 77 84 85
Not Completed 26 16 19
Reason Not Completed
Lost to Follow-up             4             2             2
Withdrawal by Subject             11             3             8
Death             0             0             1
Sponsor decision             4             1             4
Subject choice/Subject moved             2             1             1
Investigator decision             0             1             0
AE/SAEs             2             1             1
Received prohibited medication             1             0             0
Did not complete all 3 follow-up visits             2             5             2
Inadequate venous access             0             2             0
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg Total
Hide Arm/Group Description Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks. Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks. Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks. Total of all reporting groups
Overall Number of Baseline Participants 103 100 104 307
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized into the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 103 participants 100 participants 104 participants 307 participants
39.2  (12.9) 39.3  (12.0) 40.8  (11.6) 39.8  (12.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 103 participants 100 participants 104 participants 307 participants
Female
94
  91.3%
94
  94.0%
99
  95.2%
287
  93.5%
Male
9
   8.7%
6
   6.0%
5
   4.8%
20
   6.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 103 participants 100 participants 104 participants 307 participants
American Indian or Alaskan Native 0 4 1 5
Asian 13 3 6 22
Black or African American 12 19 10 41
Native Hawaiian or Other Pacific Islander 0 0 0 0
White 41 36 51 128
Other 36 37 36 109
Multiple category checked 1 1 0 2
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 103 participants 100 participants 104 participants 307 participants
BRAZIL 3 0 0 3
BULGARIA 3 2 4 9
COLOMBIA 16 10 18 44
CZECH REPUBLIC 1 0 2 3
HUNGARY 2 5 3 10
INDIA 2 1 0 3
MEXICO 4 7 5 16
PERU 15 22 13 50
POLAND 11 9 12 32
ROMANIA 1 0 1 2
SOUTH KOREA 3 0 3 6
TAIWAN 7 2 3 12
UKRAINE 7 4 11 22
UNITED STATES OF AMERICA 28 38 29 95
Baseline weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 103 participants 100 participants 104 participants 307 participants
68.08  (18.98) 69.62  (17.09) 70.74  (17.29) 69.48  (17.79)
1.Primary Outcome
Title Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The modified Intent-To-Treat (mITT) population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 102 99 104
Measure Type: Number
Unit of Measure: Percentage of Participants
17.6 34.3 28.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Anifrolumab 300 mg
Comments All-comers
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.38
Confidence Interval (2-Sided) 90%
1.33 to 4.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Anifrolumab 1000 mg
Comments All-comers
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.94
Confidence Interval (2-Sided) 90%
1.08 to 3.49
Estimation Comments [Not Specified]
2.Primary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 76 75 78
Measure Type: Number
Unit of Measure: Percentage of Participants
13.2 36 28.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Anifrolumab 300 mg
Comments High
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.55
Confidence Interval (2-Sided) 90%
1.72 to 7.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Anifrolumab 1000 mg
Comments High
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.65
Confidence Interval (2-Sided) 90%
1.27 to 5.53
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 102 99 104
Measure Type: Number
Unit of Measure: Percentage of Participants
25.5 51.5 38.5
4.Secondary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 64 55 63
Measure Type: Number
Unit of Measure: Percentage of Participants
26.6 56.4 31.7
5.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included participants who received any investigational product. Here, "N" signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 101 99 105
Measure Type: Number
Unit of Measure: Participants
TEAEs 78 84 90
TESAEs 19 16 18
AESIs 12 10 15
6.Secondary Outcome
Title Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included participants who received any investigational product. Here, "N" signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 101 99 105
Measure Type: Number
Unit of Measure: Participants
Neutrophil count increased 0 1 3
Leukocytosis 0 1 2
Leukopenia 2 0 3
Neutropenia 0 0 3
Anaemia 0 0 2
Iron deficiency anaemia 0 1 1
Lymphopenia 0 0 2
Microcytic anaemia 1 0 2
Thrombocytosis 0 1 0
White blood cell count increased 0 0 1
Monocyte count increased 0 0 1
Hypochromic anaemia 1 0 0
Hyperglycaemia 1 3 1
Hypokalaemia 2 3 0
Hepatic enzyme increased 1 0 3
Hypocalcaemia 0 1 1
Lipid metabolism disorder 0 1 1
Alanine aminotransferase increased 0 1 1
Aspartate aminotransferase increased 0 2 0
Blood creatine phosphokinase increased 0 1 1
Hyperlipidaemia 1 0 1
Hypertriglyceridaemia 2 1 0
Hyponatraemia 0 0 1
Blood alkaline phosphatase increased 0 1 0
Gamma-glutamyltransferase increased 0 1 0
Glomerular filtration rate decreased 0 1 0
Transaminases increased 1 0 1
Dyslipidaemia 1 0 0
Alanine aminotransferase abnormal 1 0 0
Aspartate aminotransferase abnormal 1 0 0
Blood triglycerides abnormal 1 0 0
Glomerular filtration rate increased 1 0 0
7.Secondary Outcome
Title Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included participants who received any investigational product. Here, "N" signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 101 99 105
Measure Type: Number
Unit of Measure: Participants
Hypertension 7 3 2
Pyrexia 5 0 3
Blood pressure increased 0 2 1
Blood pressure decreased 0 0 1
Hypotension 0 1 0
Secondary hypertension 0 0 1
Weight increased 0 0 1
Blood pressure abnormal 1 0 0
Chills 1 0 0
Hypertensive emergency 1 0 0
8.Secondary Outcome
Title Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included participants who received any investigational product. Here, "N" signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 101 99 105
Measure Type: Number
Unit of Measure: Participants
0 0 2
9.Secondary Outcome
Title Percentage of SLE Participants With Positive Anti-drug Antibody (ADA)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included participants who received any investigational product. Here, "N" and "n" signifies evaluable participants for this outcome measure and for specified category of the arms respectively. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in Anifrolumab 1000 mg group.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 101 99 105
Measure Type: Number
Unit of Measure: Percentage of Participants
Day 1 (n=100,98,105) 1.0 1.0 1.9
Day 85 (n=91,93,98) 1.1 0.0 0.0
Day 141 (n=84,94,93) 2.4 0.0 2.2
Day 169 (n=81,89,92) 2.5 0.0 1.1
Day 253 (n=72,86,86) 0.0 1.2 0.0
Day 337 (n=70,87,76) 0.0 1.1 0.0
Day 365 (n=85,96,94) 0.0 1.0 1.1
Day 396 (n=78,88,90) 0.0 2.3 0.0
Day 422 (n=76,86,77) 1.3 5.8 0.0
Any Visit Post Baseline (n= 99,98,102) 3.0 5.1 2.0
10.Secondary Outcome
Title Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 102 99 104
Mean (Standard Deviation)
Unit of Measure: Ratio
Day 29 (n= 68, 66, 73) -0.753  (44.678) 70.194  (40.028) 82.056  (16.108)
Day 85 (n= 63, 62, 72) -5.412  (44.354) 72.639  (34.443) 79.350  (40.428)
Day 141 (n= 59, 64, 68) -25.411  (78.391) 73.662  (36.684) 88.569  (10.364)
Day 169 (n= 56, 60, 66) -17.122  (67.603) 77.364  (30.733) 88.126  (10.278)
Day 253 (n= 50, 60, 61) -9.908  (49.826) 73.972  (41.267) 86.099  (15.615)
Day 337 (n= 49, 59, 53) -13.784  (45.541) 79.363  (28.803) 87.811  (8.410)
Day 365 (n= 58, 66, 68) -6.428  (50.358) 72.796  (35.552) 81.115  (53.121)
Day 396 (n= 56, 61, 64) -22.106  (64.529) 11.510  (56.385) 72.291  (31.182)
Day 422 (n= 53, 57, 55) -31.777  (70.173) -0.836  (44.596) 37.532  (66.339)
11.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
Arm/Group Title Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 98 104
Mean (Standard Deviation)
Unit of Measure: micrograms/milliliter (mcg/mL)
Day 1 (n=98,104) 82.8  (64.5) 248  (79.9)
Day 169 (n=86,87) 110  (63.7) 375  (137)
Day 337 (n=83,67) 127  (64.6) 439  (140)
12.Secondary Outcome
Title Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
Arm/Group Title Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 81 86
Median (Full Range)
Unit of Measure: Ratio
Day 169 (n=81,86)
1.36
(0.0367 to 3680)
1.43
(0.211 to 191)
Day 337 (n=78,66)
1.56
(0.132 to 7050)
1.76
(0.492 to 240)
13.Secondary Outcome
Title Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
Arm/Group Title Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 95 99
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter
Day 29 (n=95,99) 7.95  (6.17) 46.8  (24.6)
Day 169 (n=87,87) 18.4  (12.9) 110  (60.5)
Day 365 (n=83,71) 23.6  (15.5) 154  (89.2)
14.Secondary Outcome
Title Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
Arm/Group Title Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description:
Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
Overall Number of Participants Analyzed 82 86
Median (Full Range)
Unit of Measure: Ratio
Day 169 (n=82,86)
2.49
(0.0599 to 1250)
2.29
(0.299 to 30.1)
Day 365 (n=79,70)
3.06
(0.00816 to 1130)
3.02
(0.672 to 11.7)
Time Frame Day 1 (Baseline) to Day 422 (End of Study)
Adverse Event Reporting Description 1 participant from placebo arm inadvertently received one dose of anifrolumab 1000 milligram (mg).
 
Arm/Group Title Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Hide Arm/Group Description Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks. Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks. Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
All-Cause Mortality
Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/101 (18.81%)      16/99 (16.16%)      18/105 (17.14%)    
Cardiac disorders       
Cardiac tamponade † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Myocardial infarction † 1  0/101 (0.00%)  0 0/99 (0.00%)  0 1/105 (0.95%)  1
Myocardial ischaemia † 1  1/101 (0.99%)  2 0/99 (0.00%)  0 0/105 (0.00%)  0
Ear and labyrinth disorders       
Vertigo † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Endocrine disorders       
Goitre † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Eye disorders       
Retinal disorder † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Colitis † 1  0/101 (0.00%)  0 0/99 (0.00%)  0 1/105 (0.95%)  1
Pancreatitis † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Vomiting † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
General disorders       
Chest pain † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 3/105 (2.86%)  3
Oedema peripheral † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Pyrexia † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Infections and infestations       
Appendicitis † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 1/105 (0.95%)  1
Cellulitis † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Endocarditis † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Gastroenteritis † 1  1/101 (0.99%)  1 1/99 (1.01%)  1 0/105 (0.00%)  0
Haematoma infection † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Herpes zoster † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 1/105 (0.95%)  1
Influenza † 1  0/101 (0.00%)  0 2/99 (2.02%)  2 1/105 (0.95%)  1
Lobar pneumonia † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Meningitis cryptococcal † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Peritonitis † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Pneumonia † 1  2/101 (1.98%)  2 2/99 (2.02%)  2 2/105 (1.90%)  2
Septic shock † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Subcutaneous abscess † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Upper respiratory tract infection † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Urinary tract infection † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Injury, poisoning and procedural complications       
Hand fracture † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Systemic lupus erythematosus † 1  6/101 (5.94%)  6 3/99 (3.03%)  3 3/105 (2.86%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Invasive ductal breast carcinoma † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Lung neoplasm malignant † 1  0/101 (0.00%)  0 0/99 (0.00%)  0 1/105 (0.95%)  1
Uterine leiomyoma † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 1/105 (0.95%)  1
Nervous system disorders       
Cerebral infarction † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Headache † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 2/105 (1.90%)  2
Ischaemic stroke † 1  2/101 (1.98%)  2 0/99 (0.00%)  0 0/105 (0.00%)  0
Migraine † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Myelitis transverse † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Psychiatric disorders       
Suicide attempt † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Renal and urinary disorders       
Oedematous kidney † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Dyspnoea † 1  0/101 (0.00%)  0 1/99 (1.01%)  1 0/105 (0.00%)  0
Pleural effusion † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Pulmonary embolism † 1  0/101 (0.00%)  0 0/99 (0.00%)  0 1/105 (0.95%)  1
Respiratory disorder † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Vascular disorders       
Hypertensive emergency † 1  1/101 (0.99%)  1 0/99 (0.00%)  0 0/105 (0.00%)  0
Secondary hypertension † 1  0/101 (0.00%)  0 0/99 (0.00%)  0 1/105 (0.95%)  1
Vasculitis † 1  2/101 (1.98%)  3 0/99 (0.00%)  0 0/105 (0.00%)  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   36/101 (35.64%)      40/99 (40.40%)      46/105 (43.81%)    
Gastrointestinal disorders       
Diarrhoea † 1  4/101 (3.96%)  4 4/99 (4.04%)  5 8/105 (7.62%)  8
Infections and infestations       
Bronchitis † 1  4/101 (3.96%)  4 7/99 (7.07%)  7 9/105 (8.57%)  11
Nasopharyngitis † 1  4/101 (3.96%)  4 12/99 (12.12%)  15 12/105 (11.43%)  20
Upper respiratory tract infection † 1  10/101 (9.90%)  13 12/99 (12.12%)  14 11/105 (10.48%)  20
Urinary tract infection † 1  11/101 (10.89%)  18 15/99 (15.15%)  16 7/105 (6.67%)  12
Nervous system disorders       
Headache † 1  13/101 (12.87%)  21 12/99 (12.12%)  14 12/105 (11.43%)  17
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gabor Illei, MD, Senior Director
Organization: MedImmune, LLC
Phone: 301-398-0000
EMail: illeig@Medimmune.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01438489    
Other Study ID Numbers: CD-IA-MEDI-546-1013
First Submitted: September 9, 2011
First Posted: September 22, 2011
Results First Submitted: July 5, 2016
Results First Posted: August 15, 2016
Last Update Posted: October 7, 2016