Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
TULIP SLE LTE
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.
1 other identifier
interventional
559
24 countries
175
Brief Summary
The purpose of this study is to characterise long-term safety and tolerability of intravenous anifrolumab.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2016
Longer than P75 for phase_3
175 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 6, 2016
CompletedFirst Posted
Study publicly available on registry
June 9, 2016
CompletedStudy Start
First participant enrolled
June 30, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 21, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 21, 2021
CompletedResults Posted
Study results publicly available
January 13, 2023
CompletedJanuary 13, 2023
December 1, 2022
5.5 years
June 6, 2016
December 19, 2022
December 19, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Exposure-adjusted Incidence Rates (EAIRs) of Adverse Events of Special Interest (AESIs)
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.
Up to a maximum of 1114 days
EAIRs of Serious Adverse Events (SAEs)
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.
Up to a maximum of 1114 days
Study Arms (2)
Anifrolumab
EXPERIMENTALAnifrolumab
Placebo
PLACEBO COMPARATORPlacebo
Interventions
Anifrolumab IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses
Placebo IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses
Eligibility Criteria
You may qualify if:
- 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)
- Adequate peripheral venous access
- 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.
- Meets the following TB criteria:
- 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
- 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
- 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)
- 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
- In the opinion of the Investigator, subject must be able to comprehend the ICF and all protocol related assessments
You may not qualify if:
- Receipt of any of the following within the last 60 days:
- Azathioprine \>200 mg/day
- Mycophenolate mofetil \>2.0 g/day /mycophenolic acid \>1.44 g/day
- Oral, subcutaneous, or intramuscular methotrexate \>25 mg/week
- Mizoribine \>150 mg/day
- 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
- Receipt of any of the following:
- 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)
- Bacillus Calmette-Guerin (BCG) vaccine between the end of Studies D3461C00004 or D3461C00005 and Day 1/Visit 1
- Active severe SLE-driven renal or neuropsychiatric disease
- Any underlying condition that predisposes the subject to infection, including history of/current human immunodeficiency virus (HIV) infection
- 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.
- Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years of Day 1/Visit 1
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- PRA Health Sciencescollaborator
Study Sites (175)
Research Site
Birmingham, Alabama, 35294-3280, United States
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El Cajon, California, 92020, United States
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Hemet, California, 92543, United States
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La Jolla, California, 92037, United States
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Los Alamitos, California, 90720, United States
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Los Angeles, California, 90024, United States
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San Leandro, California, 94578, United States
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Thousand Oaks, California, 91360, United States
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Upland, California, 91786, United States
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Aurora, Colorado, 80045, United States
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Denver, Colorado, 80230, United States
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Bridgeport, Connecticut, 06606, United States
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Brandon, Florida, 33511, United States
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DeBary, Florida, 32713, United States
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Miami, Florida, 33136, United States
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Miami, Florida, 33180, United States
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Ormond Beach, Florida, 32174, United States
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Tampa, Florida, 33614, United States
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Vero Beach, Florida, 32960, United States
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Atlanta, Georgia, 30322, United States
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Decatur, Georgia, 30033, United States
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Lawrenceville, Georgia, 30046, United States
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Marietta, Georgia, 30060, United States
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Boise, Idaho, 83702, United States
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Idaho Falls, Idaho, 83404, United States
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Cumberland, Maryland, 21502, United States
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Hagerstown, Maryland, 21740, United States
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Grand Rapids, Michigan, 49546, United States
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Minneapolis, Minnesota, 55455-0341, United States
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Nashua, New Hampshire, 03060, United States
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Freehold, New Jersey, 07728, United States
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Las Cruces, New Mexico, 88011, United States
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Brooklyn, New York, 11201, United States
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Great Neck, New York, 11021, United States
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New Hyde Park, New York, 11042, United States
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New York, New York, 10016, United States
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New York, New York, 10021, United States
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New York, New York, 10032, United States
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Charlotte, North Carolina, 28210, United States
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Charlotte, North Carolina, 28277, United States
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Greenville, North Carolina, 27834, United States
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Raleigh, North Carolina, 27617, United States
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Middleburg Heights, Ohio, 44130, United States
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Oklahoma City, Oklahoma, 73102, United States
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Oklahoma City, Oklahoma, 73104, United States
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Philadelphia, Pennsylvania, 19140, United States
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Pittsburgh, Pennsylvania, 15213, United States
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Reading, Pennsylvania, 19610, United States
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North Charleston, South Carolina, 29406, United States
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Memphis, Tennessee, 38104, United States
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Memphis, Tennessee, 38119, United States
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Amarillo, Texas, 79124, United States
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Austin, Texas, 78726, United States
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Austin, Texas, 78745, United States
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Dallas, Texas, 75231, United States
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Houston, Texas, 77004, United States
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Houston, Texas, 77034, United States
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Houston, Texas, 77074, United States
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Mesquite, Texas, 75150, United States
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Stafford, Texas, 77477, United States
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Spokane, Washington, 99204, United States
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Milwaukee, Wisconsin, 53217, United States
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Mendoza, 5500, Argentina
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Quilmes, 1878, Argentina
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San Miguel de Tucumán, T4000AXL, Argentina
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Fitzroy, 3065, Australia
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Kogarah, 2217, Australia
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Plovdiv, 4002, Bulgaria
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Plovdiv, 4003, Bulgaria
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Hamilton, Ontario, L8S 4K1, Canada
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Rimouski, Quebec, G5L 5T1, Canada
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Osorno, 5311092, Chile
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Santiago, 8320000, Chile
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Viña del Mar, 2520997, Chile
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Armenia, 630004, Colombia
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Barranquilla, 080002, Colombia
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Medellín, 050021, Colombia
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Bordeaux, 33076, France
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Lille, 59037, France
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Montpellier, 34295, France
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Paris, 75014, France
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Paris, 75651, France
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Pessac, 33604, France
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Berlin, 10117, Germany
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Frankfurt am Main, 60528, Germany
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Hamburg, 20246, Germany
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Jena, 07747, Germany
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Kirchheim, 73230, Germany
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Mainz Am Rhein, 55131, Germany
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Budapest, 1097, Hungary
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Debrecen, 4032, Hungary
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Szeged, 6725, Hungary
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Zalaegerszeg, 8900, Hungary
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Haifa, 31048, Israel
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Haifa, 31096, Israel
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Jerusalem, 91120, Israel
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Kfar Saba, 49281, Israel
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Tel Aviv, 64239, Israel
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Chiba, 260-8712, Japan
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Chūōku, 104-8560, Japan
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Fukuoka, 810-0065, Japan
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Fukuoka, 810-8539, Japan
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Hiroshima, 730-8619, Japan
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Kitakyushu-shi, 807-8556, Japan
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Kurashiki-shi, 710-8522, Japan
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Meguro-ku, 152-8902, Japan
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Meguro-ku, 153-8515, Japan
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Nagasaki, 852-8501, Japan
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Omura-shi, 856-8562, Japan
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Sapporo, 060-8648, Japan
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Sasebo-shi, 857-1195, Japan
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Sendai, 980-8574, Japan
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Shinjuku-ku, 160-8582, Japan
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Kaunas, LT-50009, Lithuania
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Klaipėda, LT-92288, Lithuania
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Chihuahua City, 31000, Mexico
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León, 37000, Mexico
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Mexico City, 014080, Mexico
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Mérida, 97000, Mexico
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México, 06700, Mexico
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San Luis Potosí City, 78213, Mexico
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Arequipa, 04000, Peru
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Lima, 15023, Peru
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Lima, 15033, Peru
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Lima, 15046, Peru
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Lima, 15073, Peru
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Lima, 15102, Peru
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Bialystok, 15-297, Poland
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Bydgoszcz, 85 168, Poland
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Kościan, 64-000, Poland
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Krakow, 31-011, Poland
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Lublin, 20-607, Poland
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Nadarzyn, 05-830, Poland
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Starachowice, 27-200, Poland
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Szczecin, 71-252, Poland
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Ustroń, 43-450, Poland
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Warsaw, 02-118, Poland
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Brasov, 500283, Romania
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Bucharest, 011172, Romania
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Cluj-Napoca, 400006, Romania
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Galati, 800578, Romania
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Târgu Mureş, 540136, Romania
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Smolensk, 214015, Russia
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Tolyatti, 445039, Russia
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Vladimir, 600023, Russia
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Yaroslavl, 150003, Russia
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Cape Town, 7500, South Africa
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Johannesburg, 2021, South Africa
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Stellenbosch, 7600, South Africa
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Daejeon, 35015, South Korea
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Gwangju, 61469, South Korea
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Jeju City, 690-767, South Korea
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Seoul, 05030, South Korea
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Seoul, 06591, South Korea
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Seoul, 07345, South Korea
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Suwon, 16499, South Korea
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Barcelona, 08035, Spain
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Getafe, 28905, Spain
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Mérida, 06800, Spain
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Servilla, 41014, Spain
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Vigo, 36200, Spain
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Kaohsiung City, 83301, Taiwan
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Taichung, 40705, Taiwan
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Taipei, 10002, Taiwan
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Kyiv, 01601, Ukraine
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Kyiv, 03680, Ukraine
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Lviv, 79011, Ukraine
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Ternopil, 46001, Ukraine
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Uzhhorod, 88018, Ukraine
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Vinnytsia, 21018, Ukraine
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Zaporizhzhia, 69600, Ukraine
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Doncaster, DN2 5LT, United Kingdom
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Leeds, LS7 4SA, United Kingdom
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London, SE1 9RT, United Kingdom
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Manchester, M13 9WL, United Kingdom
Related Publications (3)
Strand V, Kalunian KC, Lee KW, Seo C, Abreu G, Tummala R, Al-Mossawi H, Duncan EA, Lindholm C. Long-term effect of anifrolumab on patient-reported outcomes in systemic lupus erythematosus (TULIP-LTE): a randomised, placebo-controlled, phase 3 long-term extension trial. Lancet Rheumatol. 2025 Jul;7(7):e485-e494. doi: 10.1016/S2665-9913(25)00022-0. Epub 2025 May 2.
PMID: 40324450DERIVEDTanaka Y, Atsumi T, Okada M, Miyamura T, Ishii T, Nishiyama S, Matsumura R, Kawakami A, Hayashi N, Abreu G, Yavuz S, Lindholm C, Al-Mossawi H, Takeuchi T. The long-term safety and tolerability of anifrolumab for patients with systemic lupus erythematosus in Japan: TULIP-LTE subgroup analysis. Mod Rheumatol. 2024 Jul 6;34(4):720-731. doi: 10.1093/mr/road092.
PMID: 37706527DERIVEDKalunian KC, Furie R, Morand EF, Bruce IN, Manzi S, Tanaka Y, Winthrop K, Hupka I, Zhang LJ, Werther S, Abreu G, Hultquist M, Tummala R, Lindholm C, Al-Mossawi H. A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. Arthritis Rheumatol. 2023 Feb;75(2):253-265. doi: 10.1002/art.42392. Epub 2022 Nov 11.
PMID: 36369793DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Kenneth Kalunian, MD
University of California, San Diego
- STUDY DIRECTOR
Raj Tummala, MD
AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 6, 2016
First Posted
June 9, 2016
Study Start
June 30, 2016
Primary Completion
December 21, 2021
Study Completion
December 21, 2021
Last Updated
January 13, 2023
Results First Posted
January 13, 2023
Record last verified: 2022-12