Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus - TULIP SLE LTE

Study identifier:D3461C00009

ClinicalTrials.gov identifier:NCT02794285

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multicentre, Randomised, Double-blind, Placebo-Controlled Phase 3 Extension Study to Characterise the Long-term Safety and Tolerability of Anifrolumab in Adult Subjects with Active Systemic Lupus Erythematosus.

Medical condition

Active Systemic Lupus Erythematosus

Phase

Phase 3

Healthy volunteers

Study drug

Placebo

Sex

All

Actual Enrollment

559

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 30 Jun 2016

Primary Completion Date: 21 Dec 2021

Study Completion Date: 21 Dec 2021

Study design

Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2022 by AstraZeneca

Collaborators

PRA Health Sciences

Inclusion and exclusion criteria

Inclusion Criteria

1. Subjects who have qualified for and received investigational product (anifrolumab or placebo) and completed the treatment period in Studies D3461C00004 or D3461C00005 (through Week 52)
2. Adequate peripheral venous access
3. Females with an intact cervix should have documentation of a Pap smear with no documented malignancy within 90 days before Day 1/Visit 1 or 30 days following Day 1/Visit 1. Since access to a Pap smear may vary by country, the Sponsor recommends that local guidelines for obtaining Pap smears in subjects who have received immunomodulators or immunosuppressive treatment be followed.
4. Meets the following TB criteria:
(a) Negative QuantiFERON®-TB Gold [QFT-G] test result for TB obtained from the study central laboratory at Week 52 of Studies D3461C00004 or D3461C00005; OR
(b) Newly positive QFT-G test result at Week 52 of Studies D3461C00004 or D3461C00005 from the study central laboratory. A chest x-ray must be performed. If the chest x-ray shows no evidence of active TB, and the subject has no symptoms or medical history consistent with active TB, the subject must have a retest. If the retest is positive, the subject must start on prophylaxis within 30 days of randomisation but prior to the second dose of investigational product (Visit 2/Week 4); OR
(c) Positive but not newly positive QFT-G test at Week 52 of Studies D3461C00004 or D3461C00005. The subject must have been diagnosed with latent TB and must have documentation confirming initiation of appropriate treatment OR initiate treatment for latent TB within 30 days of randomization, but prior to the second dose of investigational product administration (Visit 2/Week 4)
(d) Newly indeterminate (confirmed on retest unless prior positive QFT G was documented, along with completed treatment for latent TB) or indeterminate but not newly indeterminate QFT-G test result at Week 52 of Studies D3461C00004 or D3461C00005 from the study central laboratory with ongoing QFT-G testing for TB according to the Study Plan
5. In the opinion of the Investigator, subject must be able to comprehend the ICF and all protocol related assessments

Exclusion Criteria

1. Receipt of any of the following within the last 60 days:
(a) Azathioprine >200 mg/day
(b)Mycophenolate mofetil >2.0 g/day /mycophenolic acid >1.44 g/day
(c) Oral, subcutaneous, or intramuscular methotrexate >25 mg/week
(d) Mizoribine >150 mg/day
2. Receipt of any investigational product (small molecule or biologic agent other than anifrolumab) within 4 weeks or 5 half-lives prior to Day 1/Visit 1, whichever is greater
3. Receipt of any of the following:
(a) Any live or attenuated vaccine within 8 weeks prior to Day 1/Visit 1 (administration of killed vaccines is acceptable, the Sponsor recommends Investigators ensure all subjects are up to date on required vaccinations, including influenza [inactivated/recombinant] vaccine prior to study entry)
(b) Bacillus Calmette-Guerin (BCG) vaccine between the end of Studies D3461C00004 or D3461C00005 and Day 1/Visit 1
4. Active severe SLE-driven renal or neuropsychiatric disease
5. Any underlying condition that predisposes the subject to infection, including history of/current human immunodeficiency virus (HIV) infection
6. Subjects with Hepatitis B core antibody (HBcAb) positivity at enrolment of Studies D3461C00004 or D3461C00005 will be tested every 3 months for Hepatitis B virus (HBV) DNA. To remain eligible in the LTE study, subject HBV DNA levels must remain below the lower limit of quantitation as per the central laboratory.
7. Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years of Day 1/Visit 1

Location

Research Site

Kogarah, Australia, 2217

Location

Research Site

Haifa, Israel, 31048

Location

Research Site

Fitzroy, Australia, 3065

Location

Research Site

Vladimir, Russian Federation, 600023

Location

Research Site

Tolyatti, Russian Federation, 445039

Location

Research Site

Denver, CO, United States, 80230

Location

Research Site

Hemet, CA, United States, 92543

Location

Research Site

Greenville, NC, United States, 27834

Arms	Assigned Interventions
Experimental: Anifrolumab Anifrolumab	Biological/Vaccine: Anifrolumab Anifrolumab IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses
Placebo Comparator: Placebo Placebo	Drug: Placebo Placebo IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This long-term extension (LTE) study was conducted at 176 study centres in 24 countries.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The LTE population was comprised of participants who had completed the 52-week double-blind treatment period in one of the Phase III feeder studies (D3461C00004 [NCT02446899] or D3461C00005 [NCT02446912]), met all LTE eligibility criteria, and were willing to continue into the extension study.

Reporting Groups

	Description
Randomised Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an intravenous (IV) infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.
Placebo Feeder + Placebo LTE	Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

Participant Flow: Overall Study

	Randomised Anifrolumab 300 mg	Placebo Feeder + Placebo LTE	Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
STARTED	257	112	111	67
COMPLETED	178	54	69	41
NOT COMPLETED	79	58	42	26
Adverse Event	11	4	5	8
Condition Under Investigation Improved	1	0	0	0
Condition Under Investigation Worsened	0	2	1	0
Death	2	1	2	0
Development of Study-specific Withdrawal Criteria	1	0	0	1
Failure to Meet Randomisation Criteria	0	0	1	0
Lack of Efficacy	10	6	3	3
Lost to Follow-up	5	6	3	1
Severe Non-compliance to Protocol	1	2	1	0
Withdrawal by Subject	38	29	20	12
Missing	1	0	0	0
Due to COVID-19 Pandemic	7	2	4	0
Other - Not Due to COVID-19 Pandemic	2	6	2	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Full Analysis Set (FAS) – LTE Study: consisted of all participants who were randomised and received at least 1 dose of investigational product in the LTE Study.

Reporting Groups

	Description
Randomised Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.
Placebo Feeder + Placebo LTE	Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

Baseline Measures

	Randomised Anifrolumab 300 mg	Placebo Feeder + Placebo LTE	Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE	Total
Number of Participants [units: Participants]	257	112	111	67	547
Age Continuous [units: Years] Mean ± Standard Deviation	43.4 ± 11.51	41.4 ± 11.46	42.2 ± 12.24	42.4 ± 11.70	42.6 ± 11.67
Age Categorical [units: ]
<=18 years	0	0	0	0	0
Between 18 and 65 years	247	111	107	65	530
>=65 years	10	1	4	2	17
Sex: Female, Male [units: ]
Female	237	103	102	63	505
Male	20	9	9	4	42
Race/Ethnicity, Customized [units: ]
White	173	77	70	45	365
Black or African American	28	11	17	10	66
Asian	33	10	12	6	61
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
American Indian or Alaska Native	3	1	0	0	4
Other	15	11	10	6	42
Missing	5	2	2	0	9
Race/Ethnicity, Customized [units: ]
Hispanic or Latino	54	28	22	14	118
Not Hispanic or Latino	198	82	87	53	420
Missing	5	2	2	0	9

Outcome Measures

1. Primary Outcome Measure: Exposure-adjusted Incidence Rates (EAIRs) of Adverse Events of Special Interest (AESIs) [ Time Frame: Up to a maximum of 1114 days ]

Measure Type	Primary
Measure Name	Exposure-adjusted Incidence Rates (EAIRs) of Adverse Events of Special Interest (AESIs)
Measure Description	The event rate per 100 participant years was defined as the number of participants with an event divided by the sum of exposure time during the LTE study (including follow-up) in days for all participants in the analysis set multiplied by 365.25 days/year multiplied by 100. The exposure in a time period for each participant was calculated as end of period - start of period + 1. EAIRs of AESIs are presented as event rate per 100 participant years. The following AESIs were pre-defined: - Non-opportunistic serious infections - Opportunistic infections - Anaphylaxis - Malignancy - Herpes zoster - Tuberculosis (TB) (including latent TB) - Influenza - Vasculitis (non-systemic lupus erythematosus [SLE]) - Major cardiovascular events as according to the Cardiovascular Event Adjudication Committee.
Time Frame	Up to a maximum of 1114 days
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - LTE Study: consisted of all participants who were randomised and received at least 1 dose of investigational product in the LTE Study.

Reporting Groups

	Description
Randomised Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.
Placebo Feeder + Placebo LTE	Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

Measured Values

	Randomised Anifrolumab 300 mg	Placebo Feeder + Placebo LTE	Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
Number of Participants Analyzed [units:participants]	257	112	111	67
Exposure-adjusted Incidence Rates (EAIRs) of Adverse Events of Special Interest (AESIs) [units: Events per 100 participant years]	11.0	9.6	12.9	12.5

No statistical analysis provided for Exposure-adjusted Incidence Rates (EAIRs) of Adverse Events of Special Interest (AESIs)

2. Primary Outcome Measure: EAIRs of Serious Adverse Events (SAEs) [ Time Frame: Up to a maximum of 1114 days ]

Measure Type	Primary
Measure Name	EAIRs of Serious Adverse Events (SAEs)
Measure Description	EAIRs of SAEs are presented as event rate per 100 participant years. An SAE was an AE occurring during any study phase that fulfils 1 or more of the following criteria: - Results in death - Is immediately life-threatening - Requires in-patient hospitalisation or prolongation of existing hospitalisation - Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions - Is a congenital abnormality or birth defect - Is an important medical event that may jeopardise the participant or may require medical intervention to prevent one of the outcomes listed above.
Time Frame	Up to a maximum of 1114 days
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - LTE Study: consisted of all participants who were randomised and received at least 1 dose of investigational product in the LTE Study.

Reporting Groups

	Description
Randomised Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.
Placebo Feeder + Placebo LTE	Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

Measured Values

	Randomised Anifrolumab 300 mg	Placebo Feeder + Placebo LTE	Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
Number of Participants Analyzed [units:participants]	257	112	111	67
EAIRs of Serious Adverse Events (SAEs) [units: Events per 100 participant years]	8.5	11.2	10.1	10.7

No statistical analysis provided for EAIRs of Serious Adverse Events (SAEs)

Serious Adverse Events

Time Frame	Day 1 up to until follow-up visit 2 (Week 164)
Additional Description	FAS - LTE Study: consisted of all participants who were randomised and received at least 1 dose of investigational product in the LTE Study.

Reporting Groups

	Description
Randomised Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.
Placebo Feeder + Placebo LTE	Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

Serious Adverse Events

Randomised Anifrolumab 300 mg

Placebo Feeder + Placebo LTE

Placebo Feeder + Anifrolumab 300 mg LTE

Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE

Total, serious adverse events

# participants affected / at risk

56/257 (21.79%)

27/112 (24.11%)

26/111 (23.42%)

14/67 (20.90%)

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

6/257 (2.33%)

1/112 (0.89%)

3/111 (2.70%)

1/67 (1.49%)

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

6/257 (2.33%)

2/112 (1.79%)

3/111 (2.70%)

3/67 (4.48%)

Infections and infestations

COVID-19¹,^†
Only participants who were ongoing in the trial at the time the COVID-19 pandemic started are included. All participants who had completed or discontinued the trial prior to the pandemic are excluded from number of participants at risk.

# participants affected / at risk

4/257 (1.56%)

0/112 (0.00%)

2/111 (1.80%)

0/67 (0.00%)

Infections and infestations

COVID-19 pneumonia¹,^†
Only participants who were ongoing in the trial at the time the COVID-19 pandemic started are included. All participants who had completed or discontinued the trial prior to the pandemic are excluded from number of participants at risk.

# participants affected / at risk

3/257 (1.17%)

1/112 (0.89%)

3/111 (2.70%)

0/67 (0.00%)

Infections and infestations

Pyelonephritis¹,^†

# participants affected / at risk

3/257 (1.17%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

2/257 (0.78%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Dengue fever¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

1/257 (0.39%)

1/112 (0.89%)

2/111 (1.80%)

0/67 (0.00%)

Infections and infestations

Herpes zoster disseminated¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Influenza¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Infections and infestations

Ophthalmic herpes zoster¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Pelvic inflammatory disease¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Infections and infestations

Pharyngitis streptococcal¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Pneumonia bacterial¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Streptococcal urinary tract infection¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Bacterial sepsis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

2/111 (1.80%)

0/67 (0.00%)

Infections and infestations

Cellulitis staphylococcal¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Infections and infestations

Herpes zoster meningitis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Infections and infestations

Infected skin ulcer¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Infections and infestations

Ludwig angina¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Mediastinitis¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Parotitis¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Infections and infestations

Pneumocystis jirovecii pneumonia¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Infections and infestations

Pneumonia influenzal¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Infections and infestations

Pneumonia staphylococcal¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Postoperative abscess¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Infections and infestations

Postoperative wound infection¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Viral infection¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Infections and infestations

Wound infection staphylococcal¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Uterine leiomyoma¹,^†

# participants affected / at risk

2/257 (0.78%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Thyroid cancer¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basal cell carcinoma¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

2/257 (0.78%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

1/111 (0.90%)

0/67 (0.00%)

Blood and lymphatic system disorders

Iron deficiency anaemia¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Psychiatric disorders

Affect lability¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Nervous system disorders

Cerebral infarction¹,^†

# participants affected / at risk

2/257 (0.78%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Nervous system disorders

Post herpetic neuralgia¹,^†

# participants affected / at risk

2/257 (0.78%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Nervous system disorders

Intracranial aneurysm¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Nervous system disorders

Ischaemic stroke¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Nervous system disorders

Central nervous system lupus¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

1/67 (1.49%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

1/111 (0.90%)

1/67 (1.49%)

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

1/111 (0.90%)

0/67 (0.00%)

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Cardiac disorders

Myocardial ischaemia¹,^†

# participants affected / at risk

2/257 (0.78%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Cardiac disorders

Aortic valve disease¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Cardiac disorders

Bundle branch block left¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Cardiac disorders

Cardiac failure congestive¹,^†

# participants affected / at risk

1/257 (0.39%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

1/111 (0.90%)

0/67 (0.00%)

Cardiac disorders

Cardiogenic shock¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Cardiac disorders

Pericardial effusion¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Cardiac disorders

Pericarditis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Cardiac disorders

Supraventricular tachycardia¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Vascular disorders

Malignant hypertension¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Vascular disorders

Orthostatic hypotension¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Vascular disorders

Venous thrombosis limb¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

1/257 (0.39%)

1/112 (0.89%)

1/111 (0.90%)

0/67 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pleurisy¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

1/67 (1.49%)

Respiratory, thoracic and mediastinal disorders

Pulmonary hypertension¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Respiratory, thoracic and mediastinal disorders

Respiratory distress¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Gastrointestinal disorders

Enterocolitis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Gastrointestinal disorders

Haemoperitoneum¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Gastrointestinal disorders

Inguinal hernia¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Gastrointestinal disorders

Tooth impacted¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Hepatobiliary disorders

Cholecystitis acute¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Hepatobiliary disorders

Cholelithiasis¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Skin and subcutaneous tissue disorders

Urticaria¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Musculoskeletal and connective tissue disorders

Systemic lupus erythematosus¹,^†

# participants affected / at risk

6/257 (2.33%)

6/112 (5.36%)

1/111 (0.90%)

2/67 (2.99%)

Musculoskeletal and connective tissue disorders

Arthritis¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Musculoskeletal and connective tissue disorders

Pain in extremity¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Musculoskeletal and connective tissue disorders

Spinal stenosis¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Musculoskeletal and connective tissue disorders

Synovial cyst¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Musculoskeletal and connective tissue disorders

Tenosynovitis¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

2/257 (0.78%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Renal and urinary disorders

Renal impairment¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Renal and urinary disorders

Hydronephrosis¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Pregnancy, puerperium and perinatal conditions

Abortion spontaneous¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Reproductive system and breast disorders

Uterine haemorrhage¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Reproductive system and breast disorders

Cervical dysplasia¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Reproductive system and breast disorders

Heavy menstrual bleeding¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Reproductive system and breast disorders

Ovarian cyst¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Reproductive system and breast disorders

Ovarian cyst ruptured¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Reproductive system and breast disorders

Uterine prolapse¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

Reproductive system and breast disorders

Uterovaginal prolapse¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

General disorders

Non-cardiac chest pain¹,^†

# participants affected / at risk

2/257 (0.78%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

General disorders

Chest discomfort¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

General disorders

Incarcerated hernia¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

General disorders

Influenza like illness¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

General disorders

Mucosal haemorrhage¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Investigations

International normalised ratio increased¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Humerus fracture¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Overdose¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Spinal compression fracture¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Upper limb fracture¹,^†

# participants affected / at risk

1/257 (0.39%)

0/112 (0.00%)

0/111 (0.00%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Arthropod bite¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Injury, poisoning and procedural complications

Joint dislocation¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Periprocedural myocardial infarction¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Post procedural haemorrhage¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Rib fracture¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

0/111 (0.00%)

1/67 (1.49%)

Injury, poisoning and procedural complications

Spinal fracture¹,^†

# participants affected / at risk

0/257 (0.00%)

0/112 (0.00%)

1/111 (0.90%)

0/67 (0.00%)

Injury, poisoning and procedural complications

Tendon rupture¹,^†

# participants affected / at risk

0/257 (0.00%)

1/112 (0.89%)

0/111 (0.00%)

0/67 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA (24.1)

Other Adverse Events

Time Frame	Day 1 up to until follow-up visit 2 (Week 164)
Additional Description	FAS - LTE Study: consisted of all participants who were randomised and received at least 1 dose of investigational product in the LTE Study.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Randomised Anifrolumab 300 mg	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.
Placebo Feeder + Placebo LTE	Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Placebo Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE	Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

Other Adverse Events

Randomised Anifrolumab 300 mg

Placebo Feeder + Placebo LTE

Placebo Feeder + Anifrolumab 300 mg LTE

Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE

Total, other (not including serious) adverse events

# participants affected / at risk

195/257 (75.88%)

79/112 (70.54%)

81/111 (72.97%)

53/67 (79.10%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

63/257 (24.51%)

13/112 (11.61%)

29/111 (26.13%)

15/67 (22.39%)

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

57/257 (22.18%)

16/112 (14.29%)

18/111 (16.22%)

9/67 (13.43%)

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

55/257 (21.40%)

18/112 (16.07%)

22/111 (19.82%)

8/67 (11.94%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

41/257 (15.95%)

9/112 (8.04%)

17/111 (15.32%)

16/67 (23.88%)

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

24/257 (9.34%)

3/112 (2.68%)

9/111 (8.11%)

6/67 (8.96%)

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

20/257 (7.78%)

5/112 (4.46%)

12/111 (10.81%)

9/67 (13.43%)

Infections and infestations

Oral herpes¹,^†

# participants affected / at risk

19/257 (7.39%)

6/112 (5.36%)

6/111 (5.41%)

0/67 (0.00%)

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

16/257 (6.23%)

6/112 (5.36%)

12/111 (10.81%)

10/67 (14.93%)

Infections and infestations

Latent tuberculosis¹,^†

# participants affected / at risk

16/257 (6.23%)

2/112 (1.79%)

4/111 (3.60%)

1/67 (1.49%)

Infections and infestations

Influenza¹,^†

# participants affected / at risk

14/257 (5.45%)

5/112 (4.46%)

9/111 (8.11%)

5/67 (7.46%)

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

7/257 (2.72%)

7/112 (6.25%)

13/111 (11.71%)

3/67 (4.48%)

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

9/257 (3.50%)

4/112 (3.57%)

3/111 (2.70%)

4/67 (5.97%)

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

8/257 (3.11%)

3/112 (2.68%)

5/111 (4.50%)

7/67 (10.45%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

28/257 (10.89%)

11/112 (9.82%)

7/111 (6.31%)

10/67 (14.93%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

8/257 (3.11%)

3/112 (2.68%)

4/111 (3.60%)

4/67 (5.97%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

13/257 (5.06%)

4/112 (3.57%)

4/111 (3.60%)

3/67 (4.48%)

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

18/257 (7.00%)

4/112 (3.57%)

4/111 (3.60%)

7/67 (10.45%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

18/257 (7.00%)

6/112 (5.36%)

8/111 (7.21%)

5/67 (7.46%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

12/257 (4.67%)

7/112 (6.25%)

6/111 (5.41%)

2/67 (2.99%)

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

7/257 (2.72%)

2/112 (1.79%)

5/111 (4.50%)

4/67 (5.97%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

7/257 (2.72%)

7/112 (6.25%)

3/111 (2.70%)

0/67 (0.00%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

21/257 (8.17%)

9/112 (8.04%)

11/111 (9.91%)

3/67 (4.48%)

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

18/257 (7.00%)

10/112 (8.93%)

12/111 (10.81%)

9/67 (13.43%)

Musculoskeletal and connective tissue disorders

Systemic lupus erythematosus¹,^†

# participants affected / at risk

12/257 (4.67%)

2/112 (1.79%)

3/111 (2.70%)

5/67 (7.46%)

Injury, poisoning and procedural complications

Infusion related reaction¹,^†

# participants affected / at risk

17/257 (6.61%)

6/112 (5.36%)

8/111 (7.21%)

2/67 (2.99%)

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

11/257 (4.28%)

6/112 (5.36%)

4/111 (3.60%)

3/67 (4.48%)

Injury, poisoning and procedural complications

Contusion¹,^†

# participants affected / at risk

10/257 (3.89%)

3/112 (2.68%)

7/111 (6.31%)

6/67 (8.96%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA (24.1)

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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Kenneth Kalunian

University of California, San Diego

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSR Synopsis

Trial Results Summaries