Efficacy and Safety of Anifrolumab Compared to Placebo in... | NCT02446899

Name	Class
PRA Health Sciences	INDUSTRY

Description Module

Detailed Description

This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. Participants must be taking either 1 or any combination of the following: oral corticosteroids (OCS), antimalarial, and/or immunosuppressants. The study will be performed in adult participants aged 18 to 70 years of age.

Approximately 360 participants receiving SOC treatment will be randomised in a 1:1 ratio to receive a fixed intravenous dose of anifrolumab 300 mg or placebo every 4 weeks for a total of 13 doses (Week 0 to Week 48), with the primary endpoint evaluated at the Week 52 visit. Investigational product will be administered as an intravenous infusion (IV) via an infusion pump over a minimum of 30 minutes, every 4 weeks.

Label	Type	Description	Intervention Names
Anifrolumab	Experimental	Anifrolumab 300 mg intravenous infusion (IV) administered every 4 weeks for a total of 13 doses.	Biological: Anifrolumab
Placebo	Placebo Comparator	Placebo intravenous infusion (IV) administered every 4 weeks for a total of 13 doses.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Anifrolumab	Biological	Intravenous infusion (IV)	Anifrolumab
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52	Composite endpoint BICLA was defined by meeting all of the following criteria: Reduction of all baseline British Isles Lupus Assessment Group (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 new BILAG-2004 A or ≥2 new BILAG-2004 B No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of >0 points in SLEDAI-2K No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) No discontinuation of investigational product No use of restricted medications beyond the protocol allowed threshold before assessment	Baseline; Week 52

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 in the IFN Test-High Sub-group	Defined by meeting all of the following criteria: Reduction of all baseline British Isles Lupus Assessment Group (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 new BILAG-2004 A or ≥2 new BILAG-2004 B No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline to >0 points in SLEDAI-2K No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) No discontinuation of investigational product No use of restricted medications beyond the protocol allowed threshold before assessment

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Aged 18 through 70 years at the time of screening
Diagnosis of paediatric or adult SLE with a diagnosis of SLE according to the ACR 1982 revised criteria ≥24 weeks prior to signing the Informed Consent form (ICF)
Currently receiving at least 1 of the following:
1. Where prednisone is the single standard of care medication (ie, the subject is not concurrently receiving any medication listed in inclusion criterion 3(c)), a dose of oral prednisone ≥7.5 mg/day but ≤40 mg/day (or prednisone equivalent) for a minimum of 8 weeks prior to Day 1. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation
2. Where prednisone is not the single standard of care medication (ie, the subject is concurrently receiving at least one medication listed in inclusion criterion 3(c), a dose of oral prednisone (≤40 mg/day) (or prednisone equivalent) for a minimum of 2 weeks prior to signing of the ICF. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation.
3. Any of the following medications administered for a minimum of 12 weeks prior to signing the informed consent, and at a stable dose for a minimum of 8 weeks prior to signing the informed consent and through Day 1:
(i) Azathioprine ≤200 mg/day (ii) Antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150 mg/day
Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at least 1 of which must be:
1. Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay (IFA) at the central laboratory with titre ≥1:80; OR
2. Anti-dsDNA antibodies at screening elevated to above normal (including indeterminate), as per the central laboratory; OR
3. Anti-Smith (anti-Sm) antibody at screening elevated to above normal as per the central laboratory
At Screening, Disease Activity Adjudication Group confirmation of:

SLEDAI-2K Criteria: SLEDAI-2K score ≥6 points and "Clinical" SLEDAI-2K score ≥4 points. The "Clinical" SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures.
Must not have active or latent TB on either chest radiograph or by quantiferon gold test
Day 1 "Clinical" SLEDAI-2K score ≥4 points
OCS dose stable for at least 2 weeks prior to randomisation
Stable SLE SOC treatment at the time of randomisation
Women of child-bearing potential must have a negative serum β-hCG test at and negative urine pregnancy test at randomisation prior to administration of investigational product

Exclusion Criteria:

Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater
Receipt of any of the following:

(a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1
History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome.
Active severe or unstable neuropsychiatric SLE
Active severe SLE-driven renal disease
Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE or SSc.
History of, or current, inflammatory joint or skin disease other than SLE
History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the ICF
26.27. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation
Confirmed positive test for hepatitis B or hepatitis C
Any severe herpes infection at any time prior to Week 0 (Day 1)
Opportunistic infection requiring hospitalisation or intravenous antimicrobial treatment within 3 years prior to randomization
History of cancer, apart from:
1. Squamous or basal cell carcinoma of the skin that has been successfully treated
2. Cervical cancer in situ that has been successfully treated

Name	Affiliation	Role
Lilia Pineda, MD	Medical Science Director	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Covina	California	91723	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
36690388	Derived	Morand EF, Abreu G, Furie RA, Golder V, Tummala R. Lupus low disease activity state attainment in the phase 3 TULIP trials of anifrolumab in active systemic lupus erythematosus. Ann Rheum Dis. 2023 May;82(5):639-645. doi: 10.1136/ard-2022-222748. Epub 2023 Jan 23.
36018235	Derived	Bruce IN, van Vollenhoven RF, Morand EF, Furie RA, Manzi S, White WB, Abreu G, Tummala R. Sustained glucocorticoid tapering in the phase 3 trials of anifrolumab: a post hoc analysis of the TULIP-1 and TULIP-2 trials. Rheumatology (Oxford). 2023 Apr 3;62(4):1526-1534. doi: 10.1093/rheumatology/keac491.

Label	URL
Redacted CSP	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
FG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 23, 2019	Dec 19, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52

Composite endpoint BICLA was defined by meeting all of the following criteria:

Reduction of all baseline British Isles Lupus Assessment Group (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 new BILAG-2004 A or ≥2 new BILAG-2004 B
No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of >0 points in SLEDAI-2K
No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS)
No discontinuation of investigational product
No use of restricted medications beyond the protocol allowed threshold before assessment

Full Analysis Set: All participants who were randomized and received at least one dose of study drug.

Posted

Count of Participants

Participants

Baseline; Week 52

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Units	Counts
Participants	OG000180 OG001182

Title

Denominators

Categories

Title	Measurements
	OG00086 OG00157

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		0.0013	Nominal p-value.	Mean Difference (Final Values)	16.3			2-Sided	95	6.3	26.3					Superiority	The difference in estimates and associated 95% CI are weighted and are calculated using a stratified Cochran-Mantel-Haenszel (CMH) approach, with stratification factors (SLEDAI-2K score at screening [<10 points vs >= 10 points], Week 0 OCS dose [<10 mg/day vs >=10 mg/day prednisone or equivalent] and type I IFN gene signature test result at screening [high vs low]).

Secondary

Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 in the IFN Test-High Sub-group

Defined by meeting all of the following criteria:

Reduction of all baseline British Isles Lupus Assessment Group (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 new BILAG-2004 A or ≥2 new BILAG-2004 B
No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline to >0 points in SLEDAI-2K
No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS)
No discontinuation of investigational product
No use of restricted medications beyond the protocol allowed threshold before assessment

Full Analysis Set: All participants who were randomized and received at least one dose of study drug, with a high interferon (IFN) test result at baseline.

Posted

Count of Participants

Participants

Baseline; Week 52

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Secondary

Number of Participants Who Achieved and Maintained an Oral Corticosteroids (OCS) Dose of ≤7.5 mg/Day at Week 52 in the Sub-Group of Participants With Baseline OCS ≥10 mg/Day

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
No use of restricted medications beyond the protocol allowed threshold before assessment

Full Analysis Set: All participants who were randomized and received at least one dose of study drug, who had a baseline OCS dose of ≥10 mg/day.

Posted

Count of Participants

Participants

Week 40; Week 52

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Units	Counts
Participants

Secondary

Number of Participants With a ≥50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 12 in The Sub-Group of Participants With Baseline CLASI Activity Score of ≥10

50% reduction in 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
No use of restricted medications beyond the protocol allowed threshold before assessment

Full Analysis Set: All participants who were randomized and received at least one dose of study drug, and who had a CLASI activity score of ≥10 at baseline.

Posted

Count of Participants

Participants

Baseline; Week 12

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Units	Counts
Participants

Secondary

Number of Participants With ≥50% Reduction in Joint Counts at Week 52 in The Sub-group of Participants With ≥6 Swollen and ≥6 Tender Joints at Baseline

50% reduction in the number of swollen and tender joints compared to baseline was defined by meeting all of the following criteria:

Achieve ≥50% reduction from baseline in the number of swollen and tender joints, separately
No discontinuation of investigational product
No use of restricted medications beyond the protocol allowed threshold before assessment

Full Analysis Set: All participants who were randomized and received at least one dose of study drug, and who had ≥6 swollen and ≥6 tender joints at baseline.

Posted

Count of Participants

Participants

Baseline; Week 52

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Units	Counts
Participants

Secondary

Annualised Flare Rate Through 52 Weeks

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.

Full Analysis Set: All participants who were randomized and received at least one dose of study drug.

Posted

Number

95% Confidence Interval

Annualized flare rate ratio

Baseline to Week 52

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Secondary

Number of Participants With One or More Adverse Events (AEs)

An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. 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.

Full Analysis Set: All participants who were randomized and received at least one dose of study drug.

Posted

Count of Participants

Participants

Baseline to end of study (Maximum of 60 weeks)

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Units	Counts
Participants

Secondary

Number of Participants With One or More Adverse Events of Special Interest (AESIs)

An AESI is an adverse event (AE) of scientific and medical concern specific to understanding biologics. An AESI may be serious or non-serious. AESI are serious infections, including non-opportunistic serious infections, opportunistic infections, anaphylaxis, malignancy, herpes zoster, tuberculosis (TB) (including latent TB), influenza, vasculitis (non-systemic lupus erythematosus [SLE]), and major adverse cardiovascular events (MACE) (including stroke, myocardial infarction [MI], or cardiovascular death).

AESIs were collected throughout 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).

Full Analysis Set: All participants who were randomized and received at least one dose of study drug.

Posted

Count of Participants

Participants

Baseline to end of study (Maximum of 60 weeks)

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Secondary

Number of Participants With a Potentially Clinically Important Change From Baseline in Vital Sign Measurements

Vital sign measurements 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).

Full Analysis Set: All participants who were randomized and received at least one dose of study drug.

Posted

Count of Participants

Participants

Baseline to end of study (Maximum of 60 weeks)

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Units	Counts
Participants

Secondary

Number of Participants With a Potentially Clinically Important Change From Baseline in Clinical Laboratory Tests

Clinical laboratory tests were analyzed in a central clinical laboratory 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).

Full Analysis Set: All participants who were randomized and received at least one dose of study drug.

Posted

Count of Participants

Participants

Baseline to end of study (Maximum of 60 weeks)

ID	Title	Description
OG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
OG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Atrial flutter	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Chilaiditi's syndrome	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Intra-abdominal haematoma	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Oesophageal stenosis	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Influenza like illness	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Hypersensitivity	Immune system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Abscess	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Appendicitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Diverticulitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events1 affected180 at risk EG0010 events0 affected182 at risk
Gastroenteritis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0002 events2 affected180 at risk EG0010 events0 affected182 at risk
Herpes zoster	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Influenza	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Periodontitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Pneumonia	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 events3 affected180 at risk EG0017 events7 affected182 at risk
Sepsis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Sialoadenitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0012 events2 affected182 at risk
Traumatic fracture	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Blood creatinine increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
International normalised ratio increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Liver function test increased	Investigations	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0011 events1 affected182 at risk
Systemic lupus erythematosus	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0016 events6 affected182 at risk
Lip squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Panic attack	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Lupus nephritis	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Cervical dysplasia	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Vaginal ulceration	Reproductive system and breast disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Pulmonary alveolar haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 events1 affected180 at risk EG0010 events0 affected182 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Haematoma	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk
Hypotension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0000 events0 affected180 at risk EG0011 events1 affected182 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0007 events7 affected180 at risk EG00111 events10 affected182 at risk
Bronchitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00031 events23 affected180 at risk EG0018 events8 affected182 at risk
Herpes zoster	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00012 events12 affected180 at risk EG0013 events3 affected182 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00042 events28 affected180 at risk EG00131 events23 affected182 at risk
Sinusitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00021 events13 affected180 at risk EG00110 events9 affected182 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00057 events42 affected180 at risk EG00124 events19 affected182 at risk
Urinary tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG00027 events21 affected180 at risk EG00140 events26 affected182 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG00042 events25 affected180 at risk EG00127 events14 affected182 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00011 events10 affected180 at risk EG0016 events6 affected182 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG00012 events11 affected180 at risk EG0013 events3 affected182 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG00013 events11 affected180 at risk EG00123 events18 affected182 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG00011 events10 affected180 at risk EG0017 events7 affected182 at risk

ID	Title	Description
BG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
BG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).	1	180	16	180	125	180
EG001	Placebo	Matching placebo administered via an intravenous infusion (IV) every 4 weeks for up to 48 weeks (13 doses).	0	182	34	182	99	182