Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
NCT ID: NCT02446912
Last Updated: 2023-01-12
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
460 participants
INTERVENTIONAL
2015-06-09
2018-07-17
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Anifrolumab - higher dose
Anifrolumab
Anifrolumab
Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses
Placebo
Placebo
Placebo
Placebo IV administration every 4 weeks from Week 0 to Week 48
Anifrolumab - lower dose
Anifrolumab
Anifrolumab
Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses
Interventions
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Anifrolumab
Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses
Placebo
Placebo IV administration every 4 weeks from Week 0 to Week 48
Eligibility Criteria
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Inclusion Criteria
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 β-hCG test and negative urine pregnancy test at randomisation (Day 1) prior to administration of investigational product
Exclusion Criteria
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
18 Years
70 Years
ALL
No
Sponsors
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PRA Health Sciences
INDUSTRY
AstraZeneca
INDUSTRY
Responsible Party
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Principal Investigators
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Herbert Hutman, MD
Role: STUDY_DIRECTOR
Medical Science Director
Locations
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Research Site
Birmingham, Alabama, United States
Research Site
El Cajon, California, United States
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La Jolla, California, United States
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Los Alamitos, California, United States
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Thousand Oaks, California, United States
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Aurora, Colorado, United States
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Aventura, Florida, United States
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Miami, Florida, United States
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Orlando, Florida, United States
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Orlando, Florida, United States
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Ormond Beach, Florida, United States
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Plantation, Florida, United States
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Tampa, Florida, United States
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Vero Beach, Florida, United States
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Decatur, Georgia, United States
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Lawrenceville, Georgia, United States
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Marietta, Georgia, United States
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Boise, Idaho, United States
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Idaho Falls, Idaho, United States
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Baton Rouge, Louisiana, United States
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Hagerstown, Maryland, United States
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Hagerstown, Maryland, United States
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Grand Rapids, Michigan, United States
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Minneapolis, Minnesota, United States
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Nashua, New Hampshire, United States
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Freehold, New Jersey, United States
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Great Neck, New York, United States
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New Hyde Park, New York, United States
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Charlotte, North Carolina, United States
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Charlotte, North Carolina, United States
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Raleigh, North Carolina, United States
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Cleveland, Ohio, United States
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Middleburg Heights, Ohio, United States
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Oklahoma City, Oklahoma, United States
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Tulsa, Oklahoma, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Wyomissing, Pennsylvania, United States
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Charleston, South Carolina, United States
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Charleston, South Carolina, United States
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Charleston, South Carolina, United States
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Jackson, Tennessee, United States
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Memphis, Tennessee, United States
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Amarillo, Texas, United States
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Austin, Texas, United States
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Austin, Texas, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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Houston, Texas, United States
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Mesquite, Texas, United States
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San Antonio, Texas, United States
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Glendale, Wisconsin, United States
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Córdoba, , Argentina
Research Site
San Miguel de Tucumán, , Argentina
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Fitzroy, , Australia
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Kogarah, , Australia
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St Leonards, , Australia
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Belo Horizonte, , Brazil
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Juiz de Fora, , Brazil
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Porto Alegre, , Brazil
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Salvador, , Brazil
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Osorno, , Chile
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Santiago, , Chile
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Viña del Mar, , Chile
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Armenia, , Colombia
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Barranquilla, , Colombia
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Bogotá, , Colombia
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Bogotá, , Colombia
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Bucaramanga, , Colombia
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Medellín, , Colombia
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Berlin, , Germany
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Cologne, , Germany
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Dessau-RoBlau, , Germany
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Frankfurt am Main, , Germany
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Göttingen, , Germany
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Kirchheim, , Germany
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Budapest, , Hungary
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Debrecen, , Hungary
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Szeged, , Hungary
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Zalaegerszeg, , Hungary
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Haifa, , Israel
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Haifa, , Israel
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Jerusalem, , Israel
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Kfar Saba, , Israel
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Petah Tikva, , Israel
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Tel Aviv, , Israel
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Milan, , Italy
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Milan, , Italy
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Padua, , Italy
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Hamilton, , New Zealand
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Wellington, , New Zealand
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Arequipa, , Peru
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Lima, , Peru
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Lima, , Peru
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Lima, , Peru
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Lima, , Peru
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Lima, , Peru
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Lima, , Peru
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Bialystok, , Poland
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Bydgoszcz, , Poland
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Elblag, , Poland
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Krakow, , Poland
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Lublin, , Poland
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Nadarzyn, , Poland
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Poznan, , Poland
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Poznan, , Poland
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Sosnowiec, , Poland
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Starachowice, , Poland
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Szczecin, , Poland
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Ustroń, , Poland
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Warsaw, , Poland
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Warsaw, , Poland
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Brasov, , Romania
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Bucharest, , Romania
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Bucharest, , Romania
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Bucharest, , Romania
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Cluj-Napoca, , Romania
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Galati, , Romania
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Tg Mures, , Romania
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Daejeon, , South Korea
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Gwangju, , South Korea
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Jeonju, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Suwon, , South Korea
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Kaohsiung Hsien, , Taiwan
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Taichung, , Taiwan
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Taichung, , Taiwan
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Taipei, , Taiwan
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Kiev, , Ukraine
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Kyiv, , Ukraine
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Kyiv, , Ukraine
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Lviv, , Ukraine
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Lviv, , Ukraine
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Ternopil, , Ukraine
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Uzhhorod, , Ukraine
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Vinnytsia, , Ukraine
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Zaporizhzhia, , Ukraine
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Brighton, , United Kingdom
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Doncaster, , United Kingdom
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Leeds, , United Kingdom
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London, , United Kingdom
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Manchester, , United Kingdom
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Romford, , United Kingdom
Research Site
Staffordshire, , United Kingdom
Countries
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References
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Furie RA, Morand EF, Bruce IN, Manzi S, Kalunian KC, Vital EM, Lawrence Ford T, Gupta R, Hiepe F, Santiago M, Brohawn PZ, Berglind A, Tummala R; TULIP-1 study investigators. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019 Dec;1(4):e208-e219. doi: 10.1016/S2665-9913(19)30076-1. Epub 2019 Nov 11.
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.
Bruce IN, van Vollenhoven RF, Morand EF, Furie RA, Manzi S, White WB, Abreu G, Tummala R. Sustained glucocorticoid tapering in the phase 3 trials of anifrolumab: a post hoc analysis of the TULIP-1 and TULIP-2 trials. Rheumatology (Oxford). 2023 Apr 3;62(4):1526-1534. doi: 10.1093/rheumatology/keac491.
Bruce 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.
Vital 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.
Loncharich 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.
Chia 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.
Furie 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.
Furie 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.
Hannon 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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Other Identifiers
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D3461C00005
Identifier Type: -
Identifier Source: org_study_id
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