Active Systemic Lupus ErythematosusPhase 3NCT02446899
Efficacy and Safety of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
A Phase 3 study testing Anifrolumab in people with Active Systemic Lupus Erythematosus, run by AstraZeneca at 113 sites in 15 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in adult participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Active Systemic Lupus Erythematosus
- What is being tested?
- Anifrolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 373 participants
- Where
- 113 sitesin 15 countries
- Study dates
- 9 Jul 2015to 27 Sep 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
- 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.
- 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:
Show all 18Show fewer
- 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:
- Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay (IFA) at the central laboratory with titre ≥1:80; OR
- Anti-dsDNA antibodies at screening elevated to above normal (including indeterminate), as per the central laboratory; OR
- 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
Who cannot join
- 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:
- 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
Show all 16Show fewer
- 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:
- Squamous or basal cell carcinoma of the skin that has been successfully treated
- Cervical cancer in situ that has been successfully treated
Trial locations and contacts
113 sites in 15 countries.
113 sites in 15 countries
United States35 sites
Research Site
Ann Arbor, Michigan, 48109
Research Site
Arlington, Virginia, 22205
Research Site
Atlanta, Georgia, 30303
Research Site
Boston, Massachusetts, 02118
Research Site
Brandon, Florida, 33511
Research Site
Bridgeport, Connecticut, 06606
Research Site
Bridgeport, Connecticut, 6606
Research Site
Brooklyn, New York, 11201
Research Site
Covina, California, 91723
Research Site
Dallas, Texas, 75231
Research Site
Denver, Colorado, 80230
Research Site
Duncansville, Pennsylvania, 16635
Research Site
Greenville, North Carolina, 27834
Research Site
Hemet, California, 92543-4403
Research Site
Houston, Texas, 77004
Research Site
Houston, Texas, 77034
Research Site
Las Cruces, New Mexico, 88011
Research Site
Lincoln, Nebraska, 68516
Research Site
Los Angeles, California, 90095
Research Site
Memphis, Tennessee, 38163
Research Site
New York, New York, 10016
Research Site
New York, New York, 10021
Research Site
New York, New York, 10032
Research Site
Oklahoma City, Oklahoma, 73104
Research Site
Orlando, Florida, 32804
Research Site
Palm Harbor, Florida, 34684
Research Site
Pittsburgh, Pennsylvania, 15213
Research Site
San Leandro, California, 94578
Research Site
Seattle, Washington, 98122
Research Site
Spokane, Washington, 99204
Research Site
Stafford, Texas, 77477
Research Site
Tamarac, Florida, 33321
Research Site
Tampa, Florida, 33614
Research Site
Torrance, California, 90509
Research Site
Upland, California, 91786
Japan17 sites
Research Site
Chiba, 260-8712
Research Site
Chūōku, 104-8560
Research Site
Fukuoka, 810-8539
Research Site
Fukuoka, 810-8563
Research Site
Hiroshima, 730-8619
Research Site
Kitakyushu-shi, 807-8555
Research Site
Kurashiki-shi, 710-8522
Research Site
Meguro-ku, 152-8902
Research Site
Meguro-ku, 153-8515
Research Site
Nagasaki, 852-8501
Research Site
Nagoya, 460-0001
Research Site
Omura-shi, 856-8562
Research Site
Sapporo, 060-8638
Research Site
Sasebo-shi, 857-1195
Research Site
Sendai, 980-8574
Research Site
Shinjuku-ku, 160-8582
Research Site
Tsukuba, 305-8577
Spain9 sites
Research Site
Barcelona, 08035
Research Site
Getafe, 28905
Research Site
Las Palmas de Gran Canaria, 35010
Research Site
Madrid, 28046
Research Site
Madrid, 28702
Research Site
Mérida, 06800
Research Site
Santiago de Compostela, 15706
Research Site
Servilla, 41014
Research Site
Vigo, 36200
France7 sites
Research Site
Bordeaux, 33000
Research Site
Lille, 59037
Research Site
Montpellier, 34295
Research Site
Paris, 75651
Research Site
Paris, 75679
Research Site
Pessac, 33604
Research Site
Toulouse, 31000
Mexico7 sites
Research Site
Chihuahua City, 31000
Research Site
León, 37000
Research Site
Mérida, 97000
Research Site
México, 06700
Research Site
Mexico City, 014080
Research Site
Morelia, 58070
Research Site
San Luis Potosí City, 78213
Russia6 sites
Research Site
Kemerovo, 650066
Research Site
Petrozavodsk, 185019
Research Site
Smolensk, 214015
Research Site
Tolyatti, 445039
Research Site
Vladimir, 600023
Research Site
Yaroslavl, 150003
Brazil5 sites
Research Site
Goiânia, 74110-120
Research Site
Juiz de Fora, 36010 570
Research Site
São Paulo, 04032-060
Research Site
São Paulo, 05403-9000
Research Site
São Paulo, 05652-900
Germany5 sites
Research Site
Berlin, D-10117
Research Site
Hamburg, 20246
Research Site
Jena, 07747
Research Site
Mainz, 55131
Research Site
München, 80336
South Korea5 sites
Research Site
Jeju City, 690-767
Research Site
Seoul, 05030
Research Site
Seoul, 06591
Research Site
Seoul, 133792
Research Site
Suwon, 16499
Belgium4 sites
Research Site
Brussels, 1070
Research Site
Leuven, 3000
Research Site
Liège, B-4000
Research Site
Merksem, B-2170
South Africa4 sites
Research Site
Cape Town, 7500
Research Site
Johannesburg, 2188
Research Site
Johannesburg, 2193
Research Site
Stellenbosch, 7600
Argentina3 sites
Research Site
Buenos Aires, C1015ABO
Research Site
Mendoza, 5500
Research Site
Quilmes, 1878
Canada2 sites
Research Site
Hamilton, Ontario, L8S 4K1
Research Site
Rimouski, Quebec, G5L 5T1
Lithuania2 sites
Research Site
Kaunas, LT-50009
Research Site
Klaipėda, LT-92288
About this study
Official title: A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in adult participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).
Read the 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.
- Conditions
- Active Systemic Lupus Erythematosus
- Being tested
- Anifrolumab, Placebo
- Keywords
- Active Systemic Lupus Erythematosus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnifrolumabBiological
Intravenous infusion (IV)
PlaceboDrug
Intravenous infusion (IV)
| Study group | Role | What they receive |
|---|---|---|
| Anifrolumab | Experimental | Anifrolumab 300 mg intravenous infusion (IV) administered every 4 weeks for a total of 13 doses. Receives: Biological: Anifrolumab |
| Placebo | Placebo comparator | Placebo intravenous infusion (IV) administered every 4 weeks for a total of 13 doses. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline; Week 52
Secondary outcomes (9)
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
Measured: Baseline; Week 52
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
Measured: Week 40; Week 52
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
Measured: Baseline; Week 12
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
Measured: Baseline; Week 52
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.
Measured: Baseline to Week 52
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.
Measured: Baseline to end of study (Maximum of 60 weeks)
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).
Measured: Baseline to end of study (Maximum of 60 weeks)
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).
Measured: Baseline to end of study (Maximum of 60 weeks)
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).
Measured: Baseline to end of study (Maximum of 60 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2015 (estimated)
- Study start9 Jul 2015
- Primary completion27 Sep 2018
- Study completion27 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Active Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 373 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Lilia Pineda, MD, Study director, Medical Science Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02446899
- Sponsor's protocol ID
- D3461C00004
- Status last verified
- Dec 2022
- First submitted
- 14 May 2015
- Last updated
- 10 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36690388Bruce 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.
PubMed 36018235Bruce IN, Furie RA, Morand EF, Manzi S, Tanaka Y, Kalunian KC, Merrill JT, Puzio P, Maho E, Kleoudis C, Albulescu M, Hultquist M, Tummala R. Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials. Ann Rheum Dis. 2022 Jul;81(7):962-969. doi: 10.1136/annrheumdis-2021-221847. Epub 2022 May 17.
PubMed 35580976Vital EM, Merrill JT, Morand EF, Furie RA, Bruce IN, Tanaka Y, Manzi S, Kalunian KC, Kalyani RN, Streicher K, Abreu G, Tummala R. Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials. Ann Rheum Dis. 2022 Jul;81(7):951-961. doi: 10.1136/annrheumdis-2021-221425. Epub 2022 Mar 25.
PubMed 35338035Loncharich MF, Anderson CW. Interferon Inhibition for Lupus with Anifrolumab: Critical Appraisal of the Evidence Leading to FDA Approval. ACR Open Rheumatol. 2022 Jun;4(6):486-491. doi: 10.1002/acr2.11414. Epub 2022 Feb 14.
PubMed 35157371Chia YL, Zhang J, Tummala R, Rouse T, Furie RA, Morand EF. Relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2022 May 5;61(5):1900-1910. doi: 10.1093/rheumatology/keab704.
PubMed 34528084Furie R, Morand EF, Askanase AD, Vital EM, Merrill JT, Kalyani RN, Abreu G, Pineda L, Tummala R. Anifrolumab reduces flare rates in patients with moderate to severe systemic lupus erythematosus. Lupus. 2021 Jul;30(8):1254-1263. doi: 10.1177/09612033211014267. Epub 2021 May 12.
PubMed 33977796Furie R, Morand EF, Bruce IN, Isenberg D, van Vollenhoven R, Abreu G, Pineda L, Tummala R. What Does It Mean to Be a British Isles Lupus Assessment Group-Based Composite Lupus Assessment Responder? Post Hoc Analysis of Two Phase III Trials. Arthritis Rheumatol. 2021 Nov;73(11):2059-2068. doi: 10.1002/art.41778. Epub 2021 Sep 22.
PubMed 33913260Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
PubMed 33687069Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae SC, Brohawn PZ, Pineda L, Berglind A, Tummala R; TULIP-2 Trial Investigators. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-221. doi: 10.1056/NEJMoa1912196. Epub 2019 Dec 18.
PubMed 31851795
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT02446899
- Acronym / sponsor ID
- D3461C00004
- Conditions
- Active Systemic Lupus Erythematosus
- Keywords
- Active Systemic Lupus Erythematosus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 373 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 9 Jul 2015 (actual)
- Primary completion
- 27 Sep 2018 (actual)
- Study completion
- 27 Sep 2018 (actual)
- First posted
- 18 May 2015 (estimated)
- Results
- Posted 18 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab versus placebo in adult participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anifrolumab | Experimental | Biological: AnifrolumabAnifrolumab 300 mg intravenous infusion (IV) administered every 4 weeks for a total of 13 doses. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo intravenous infusion (IV) administered every 4 weeks for a total of 13 doses. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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:
- Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at least 1 of which must be:
- At Screening, Disease Activity Adjudication Group confirmation of:
Key exclusion criteria (16 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnifrolumabIntravenous infusion (IV) | Biological | Anifrolumab |
| PlaceboIntravenous infusion (IV) | Drug | Placebo |
Primary outcome
Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52
Time frame: Baseline; 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
9 secondary outcomes
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
Time frame: Baseline; Week 52
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
Time frame: Week 40; Week 52
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
Time frame: Baseline; Week 12
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
Time frame: Baseline; Week 52
Annualised Flare Rate Through 52 Weeks
Time frame: Baseline to Week 52
Number of Participants With One or More Adverse Events (AEs)
Time frame: Baseline to end of study (Maximum of 60 weeks)
Number of Participants With One or More Adverse Events of Special Interest (AESIs)
Time frame: Baseline to end of study (Maximum of 60 weeks)
Number of Participants With a Potentially Clinically Important Change From Baseline in Vital Sign Measurements
Time frame: Baseline to end of study (Maximum of 60 weeks)
Number of Participants With a Potentially Clinically Important Change From Baseline in Clinical Laboratory Tests
Time frame: Baseline to end of study (Maximum of 60 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36690388Morand 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.
- Derived from this study: PubMed 36018235Bruce 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.
- Derived from this study: PubMed 35580976Bruce IN, Furie RA, Morand EF, Manzi S, Tanaka Y, Kalunian KC, Merrill JT, Puzio P, Maho E, Kleoudis C, Albulescu M, Hultquist M, Tummala R. Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials. Ann Rheum Dis. 2022 Jul;81(7):962-969. doi: 10.1136/annrheumdis-2021-221847. Epub 2022 May 17.
- Derived from this study: PubMed 35338035Vital EM, Merrill JT, Morand EF, Furie RA, Bruce IN, Tanaka Y, Manzi S, Kalunian KC, Kalyani RN, Streicher K, Abreu G, Tummala R. Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials. Ann Rheum Dis. 2022 Jul;81(7):951-961. doi: 10.1136/annrheumdis-2021-221425. Epub 2022 Mar 25.
- Derived from this study: PubMed 35157371Loncharich MF, Anderson CW. Interferon Inhibition for Lupus with Anifrolumab: Critical Appraisal of the Evidence Leading to FDA Approval. ACR Open Rheumatol. 2022 Jun;4(6):486-491. doi: 10.1002/acr2.11414. Epub 2022 Feb 14.
- Derived from this study: PubMed 34528084Chia YL, Zhang J, Tummala R, Rouse T, Furie RA, Morand EF. Relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2022 May 5;61(5):1900-1910. doi: 10.1093/rheumatology/keab704.
- Derived from this study: PubMed 33977796Furie R, Morand EF, Askanase AD, Vital EM, Merrill JT, Kalyani RN, Abreu G, Pineda L, Tummala R. Anifrolumab reduces flare rates in patients with moderate to severe systemic lupus erythematosus. Lupus. 2021 Jul;30(8):1254-1263. doi: 10.1177/09612033211014267. Epub 2021 May 12.
- Derived from this study: PubMed 33913260Furie R, Morand EF, Bruce IN, Isenberg D, van Vollenhoven R, Abreu G, Pineda L, Tummala R. What Does It Mean to Be a British Isles Lupus Assessment Group-Based Composite Lupus Assessment Responder? Post Hoc Analysis of Two Phase III Trials. Arthritis Rheumatol. 2021 Nov;73(11):2059-2068. doi: 10.1002/art.41778. Epub 2021 Sep 22.
- Derived from this study: PubMed 33687069Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
- Derived from this study: PubMed 31851795Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae SC, Brohawn PZ, Pineda L, Berglind A, Tummala R; TULIP-2 Trial Investigators. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-221. doi: 10.1056/NEJMoa1912196. Epub 2019 Dec 18.
- Redacted CSPLink provided by the sponsor.
- Redacted SAPLink provided by the sponsor.
Related trials for Active Systemic Lupus Erythematosus
RecruitingPhase 4
Dapagliflozin in Active Lupus Nephritis
Lupus Nephritis (LN)
RecruitingPhase 1
To Evaluate the Effects of Cevostamab in Participants With Systemic Lupus Erythematosus With or Without Active Lupus Nephritis
Lupus Erythematosus, Systemic
RecruitingPhase 3
A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease
Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE)
RecruitingPhase 3
A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease (ELOWEN-2)
Systematic Lupus Erythematosus, Cutaneous Lupus Erythematosus
RecruitingPhase 2
A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis and the Safety and PK of Obinutuzumab in Pediatric Participants
Lupus Nephritis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lilia Pineda, MD study director
Medical Science Director
113 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Anifrolumab in people with Active Systemic Lupus Erythematosus, run by AstraZeneca at 113 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 113 sites in United States, Japan, Spain, France, Mexico and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Achieved the British Isles Lupus Assessment Group Based Composite Lupus Assessment (BICLA) Response at Week 52 (time frame: Baseline; Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02446899, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2023.