The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02446912




Registration number
NCT02446912
Ethics application status
Date submitted
14/05/2015
Date registered
18/05/2015
Date last updated
12/01/2023

Titles & IDs
Public title
Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
Scientific title
A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Two Doses of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
Secondary ID [1] 0 0
D3461C00005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Active Systemic Lupus Erythematosus 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Anifrolumab
Treatment: Drugs - Placebo

Experimental: Anifrolumab - higher dose - Anifrolumab

Placebo comparator: Placebo - Placebo

Experimental: Anifrolumab - lower dose - Anifrolumab


Treatment: Other: Anifrolumab
Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses

Treatment: Drugs: Placebo
Placebo IV administration every 4 weeks from Week 0 to Week 48

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index =4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules)
Timepoint [1] 0 0
Week 52
Secondary outcome [1] 0 0
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of =4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Original Analysis With Restricted Medication Rules)
Timepoint [1] 0 0
Week 52
Secondary outcome [2] 0 0
Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of =7.5 mg/Day in the Sub-group of Participants With Baseline OCS =10 mg/Day (Original Analysis With Restricted Medication Rules)
Timepoint [2] 0 0
Week 52
Secondary outcome [3] 0 0
Number of Participants With a =50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score =10 (Original Analysis With Restricted Medication Rules)
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of =4 (SRI[4]) at Week 24 (Original Analysis With Restricted Medication Rules)
Timepoint [4] 0 0
Week 24
Secondary outcome [5] 0 0
Annualized Flare Rate
Timepoint [5] 0 0
Baseline to Week 52
Secondary outcome [6] 0 0
Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Original Analysis With Restricted Medication Rules)
Timepoint [6] 0 0
Week 52
Secondary outcome [7] 0 0
Number of Participants Reporting One or More Adverse Events (AE)
Timepoint [7] 0 0
Baseline to End of Trial (Maximum of 60 weeks)
Secondary outcome [8] 0 0
Number of Participants Reporting One or More Adverse Events of Special Interest (AESI)
Timepoint [8] 0 0
Baseline to End of Trial (Maximum of 60 weeks)
Secondary outcome [9] 0 0
Number of Participants With Markedly Abnormal Vital Signs
Timepoint [9] 0 0
Baseline to End of Trial (Maximum of 60 weeks)
Secondary outcome [10] 0 0
Number of Participants With Markedly Abnormal Physical Examinations
Timepoint [10] 0 0
Baseline to End of Trial (Maximum of 60 weeks)
Secondary outcome [11] 0 0
Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Scores
Timepoint [11] 0 0
Baseline to Week 52
Secondary outcome [12] 0 0
Number of Participants With Mild To Moderate Lupus Flare Evaluated by Modified Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare Index
Timepoint [12] 0 0
Baseline to End of Trial (Maximum of 60 weeks)
Secondary outcome [13] 0 0
Number of Participants With Markedly Abnormal Laboratory Tests
Timepoint [13] 0 0
Baseline to End of Trial (Maximum of 60 weeks)
Secondary outcome [14] 0 0
Number of Participants With Suicidal Ideation or Behaviour Assessed Via the Columbia Suicide Severity Rating Scale (C-SSRS)
Timepoint [14] 0 0
Baseline to Week 52
Secondary outcome [15] 0 0
Change From Baseline in Personal Health Questionnaire Depression Scale-8 (PHQ-8) Score
Timepoint [15] 0 0
Baseline to Week 52

Eligibility
Key inclusion criteria
1. Aged 18 through 70 years at the time of screening
2. 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)
3. 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 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
4. 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 indeterminante), as per the central laboratory; OR
3. Anti-Smith (anti-Sm) antibody at screening elevated to above normal as per the central laboratory.
5. 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.
6. Must not have active or latent TB on either chest radiograph or by quantiferon gold test
7. Day 1 "Clinical" SLEDAI-2K score =4 points
8. OCS dose stable for at least 2 weeks prior to randomisation
9. Stable SLE SOC treatment at the time of randomisation
10. Women of child-bearing potential must have a negative serum ß-hCG test and negative urine pregnancy test at randomisation (Day 1) prior to administration of investigational product
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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
2. Receipt of any of the following:

(a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1
3. History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome.
4. Active severe or unstable neuropsychiatric SLE
5. Active severe SLE-driven renal disease
6. Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE or SSc.
7. History of, or current, inflammatory joint or skin disease other than SLE
8. 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
9. 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
10. Confirmed positive test for hepatitis B or hepatitis C
11. Any severe herpes infection at any time prior to Week 0 (Day 1)
12. Opportunistic infection requiring hospitalisation or intravenous antimicrobial treatment within 3 years prior to randomization
13. 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Fitzroy
Recruitment hospital [2] 0 0
Research Site - Kogarah
Recruitment hospital [3] 0 0
Research Site - St Leonards
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
New Hampshire
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Wisconsin
Country [22] 0 0
Argentina
State/province [22] 0 0
Cordoba
Country [23] 0 0
Argentina
State/province [23] 0 0
San Miguel de Tucuman
Country [24] 0 0
Brazil
State/province [24] 0 0
Belo Horizonte
Country [25] 0 0
Brazil
State/province [25] 0 0
Juiz de Fora
Country [26] 0 0
Brazil
State/province [26] 0 0
Porto Alegre
Country [27] 0 0
Brazil
State/province [27] 0 0
Salvador
Country [28] 0 0
Chile
State/province [28] 0 0
Osorno
Country [29] 0 0
Chile
State/province [29] 0 0
Santiago
Country [30] 0 0
Chile
State/province [30] 0 0
Vina del Mar
Country [31] 0 0
Colombia
State/province [31] 0 0
Armenia
Country [32] 0 0
Colombia
State/province [32] 0 0
Barranquilla
Country [33] 0 0
Colombia
State/province [33] 0 0
Bogota
Country [34] 0 0
Colombia
State/province [34] 0 0
Bucaramanga
Country [35] 0 0
Colombia
State/province [35] 0 0
Medellin
Country [36] 0 0
Germany
State/province [36] 0 0
Berlin
Country [37] 0 0
Germany
State/province [37] 0 0
Dessau-RoBlau
Country [38] 0 0
Germany
State/province [38] 0 0
Frankfurt am Main
Country [39] 0 0
Germany
State/province [39] 0 0
Göttingen
Country [40] 0 0
Germany
State/province [40] 0 0
Kirchheim
Country [41] 0 0
Germany
State/province [41] 0 0
Köln
Country [42] 0 0
Hungary
State/province [42] 0 0
Budapest
Country [43] 0 0
Hungary
State/province [43] 0 0
Debrecen
Country [44] 0 0
Hungary
State/province [44] 0 0
Szeged
Country [45] 0 0
Hungary
State/province [45] 0 0
Zalaegerszeg
Country [46] 0 0
Israel
State/province [46] 0 0
Haifa
Country [47] 0 0
Israel
State/province [47] 0 0
Jerusalem
Country [48] 0 0
Israel
State/province [48] 0 0
Kfar Saba
Country [49] 0 0
Israel
State/province [49] 0 0
Petach-Tikva
Country [50] 0 0
Israel
State/province [50] 0 0
Tel Aviv
Country [51] 0 0
Italy
State/province [51] 0 0
Milano
Country [52] 0 0
Italy
State/province [52] 0 0
Padova
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Daejeon
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Gwangju
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Jeonju-si
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Seoul
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Suwon-si
Country [58] 0 0
New Zealand
State/province [58] 0 0
Hamilton
Country [59] 0 0
New Zealand
State/province [59] 0 0
Wellington
Country [60] 0 0
Peru
State/province [60] 0 0
Arequipa
Country [61] 0 0
Peru
State/province [61] 0 0
Lima
Country [62] 0 0
Poland
State/province [62] 0 0
Bialystok
Country [63] 0 0
Poland
State/province [63] 0 0
Bydgoszcz
Country [64] 0 0
Poland
State/province [64] 0 0
Elblag
Country [65] 0 0
Poland
State/province [65] 0 0
Kraków
Country [66] 0 0
Poland
State/province [66] 0 0
Lublin
Country [67] 0 0
Poland
State/province [67] 0 0
Nadarzyn
Country [68] 0 0
Poland
State/province [68] 0 0
Poznan
Country [69] 0 0
Poland
State/province [69] 0 0
Sosnowiec
Country [70] 0 0
Poland
State/province [70] 0 0
Starachowice
Country [71] 0 0
Poland
State/province [71] 0 0
Szczecin
Country [72] 0 0
Poland
State/province [72] 0 0
Ustron
Country [73] 0 0
Poland
State/province [73] 0 0
Warszawa
Country [74] 0 0
Romania
State/province [74] 0 0
Brasov
Country [75] 0 0
Romania
State/province [75] 0 0
Bucharest
Country [76] 0 0
Romania
State/province [76] 0 0
Bucuresti
Country [77] 0 0
Romania
State/province [77] 0 0
Cluj Napoca
Country [78] 0 0
Romania
State/province [78] 0 0
Galati
Country [79] 0 0
Romania
State/province [79] 0 0
Tg Mures
Country [80] 0 0
Taiwan
State/province [80] 0 0
Kaohsiung Hsien
Country [81] 0 0
Taiwan
State/province [81] 0 0
Taichung
Country [82] 0 0
Taiwan
State/province [82] 0 0
Taipei
Country [83] 0 0
Ukraine
State/province [83] 0 0
Kiev
Country [84] 0 0
Ukraine
State/province [84] 0 0
Kyiv
Country [85] 0 0
Ukraine
State/province [85] 0 0
Lviv
Country [86] 0 0
Ukraine
State/province [86] 0 0
Ternopil
Country [87] 0 0
Ukraine
State/province [87] 0 0
Uzhgorod
Country [88] 0 0
Ukraine
State/province [88] 0 0
Vinnytsia
Country [89] 0 0
Ukraine
State/province [89] 0 0
Zaporizhzhia
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Brighton
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Doncaster
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Leeds
Country [93] 0 0
United Kingdom
State/province [93] 0 0
London
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Manchester
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Romford
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Staffordshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
PRA Health Sciences
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Herbert Hutman, MD
Address 0 0
Medical Science Director
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.