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

December 19, 2022 updated by: AstraZeneca

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.

The purpose of this study is to characterise long-term safety and tolerability of intravenous anifrolumab.

Study Overview

Status

Completed

Detailed Description

This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled extension study to characterising the long term safety and tolerability of of an intravenous treatment regimen of anifrolumab versus placebo in subjects with moderately to severely active systemic lupus erythematosus who completed a Phase 3 study (D3461C00004 or D3461C00005) through the 52-week double-blind treatment period.

Study Type

Interventional

Enrollment (Actual)

559

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Mendoza, Argentina, 5500
        • Research Site
      • Quilmes, Argentina, 1878
        • Research Site
      • San Miguel de Tucuman, Argentina, T4000AXL
        • Research Site
      • Fitzroy, Australia, 3065
        • Research Site
      • Kogarah, Australia, 2217
        • Research Site
      • Plovdiv, Bulgaria, 4003
        • Research Site
      • Plovdiv, Bulgaria, 4002
        • Research Site
    • Ontario
      • Hamilton, Ontario, Canada, L8S 4K1
        • Research Site
    • Quebec
      • Rimouski, Quebec, Canada, G5L 5T1
        • Research Site
      • Osorno, Chile, 5311092
        • Research Site
      • Santiago, Chile, 8320000
        • Research Site
      • Vina del Mar, Chile, 2520997
        • Research Site
      • Armenia, Colombia, 630004
        • Research Site
      • Barranquilla, Colombia, 080002
        • Research Site
      • Medellín, Colombia, 050021
        • Research Site
      • Bordeaux, France, 33076
        • Research Site
      • Lille, France, 59037
        • Research Site
      • Montpellier CEDEX 5, France, 34295
        • Research Site
      • Paris Cedex 13, France, 75651
        • Research Site
      • Paris cedex 14, France, 75014
        • Research Site
      • Pessac, France, 33604
        • Research Site
      • Berlin, Germany, 10117
        • Research Site
      • Frankfurt am Main, Germany, 60528
        • Research Site
      • Hamburg, Germany, 20246
        • Research Site
      • Jena, Germany, 07747
        • Research Site
      • Kirchheim, Germany, 73230
        • Research Site
      • Mainz Am Rhein, Germany, 55131
        • Research Site
      • Budapest, Hungary, 1097
        • Research Site
      • Debrecen, Hungary, 4032
        • Research Site
      • Szeged, Hungary, 6725
        • Research Site
      • Zalaegerszeg, Hungary, 8900
        • Research Site
      • Haifa, Israel, 31096
        • Research Site
      • Haifa, Israel, 31048
        • Research Site
      • Jerusalem, Israel, 91120
        • Research Site
      • Kfar Saba, Israel, 49281
        • Research Site
      • Tel Aviv, Israel, 64239
        • Research Site
      • Chiba-shi, Japan, 260-8712
        • Research Site
      • Chuo-ku, Japan, 104-8560
        • Research Site
      • Fukuoka-shi, Japan, 810-8539
        • Research Site
      • Fukuoka-shi, Japan, 810-0065
        • Research Site
      • Hiroshima-shi, Japan, 730-8619
        • Research Site
      • Kitakyushu-shi, Japan, 807-8556
        • Research Site
      • Kurashiki-shi, Japan, 710-8522
        • Research Site
      • Meguro-ku, Japan, 152-8902
        • Research Site
      • Meguro-ku, Japan, 153-8515
        • Research Site
      • Nagasaki-shi, Japan, 852-8501
        • Research Site
      • Omura-shi, Japan, 856-8562
        • Research Site
      • Sapporo-shi, Japan, 060-8648
        • Research Site
      • Sasebo-shi, Japan, 857-1195
        • Research Site
      • Sendai-shi, Japan, 980-8574
        • Research Site
      • Shinjuku-ku, Japan, 160-8582
        • Research Site
      • Daejeon, Korea, Republic of, 35015
        • Research Site
      • Gwangju, Korea, Republic of, 61469
        • Research Site
      • Jeju-si, Korea, Republic of, 690-767
        • Research Site
      • Seoul, Korea, Republic of, 06591
        • Research Site
      • Seoul, Korea, Republic of, 05030
        • Research Site
      • Seoul, Korea, Republic of, 07345
        • Research Site
      • Suwon-si, Korea, Republic of, 16499
        • Research Site
      • Kaunas, Lithuania, LT-50009
        • Research Site
      • Klaipeda, Lithuania, LT-92288
        • Research Site
      • Chihuahua, Mexico, 31000
        • Research Site
      • Leon, Mexico, 37000
        • Research Site
      • Mexico, Mexico, 06700
        • Research Site
      • Mexico D.F., Mexico, 014080
        • Research Site
      • Mérida, Mexico, 97000
        • Research Site
      • San Luis Potosí, Mexico, 78213
        • Research Site
      • Arequipa, Peru, 04000
        • Research Site
      • Lima, Peru, 15033
        • Research Site
      • Lima, Peru, 15023
        • Research Site
      • Lima, Peru, 15046
        • Research Site
      • Lima, Peru, 15073
        • Research Site
      • Lima, Peru, 15102
        • Research Site
      • Bialystok, Poland, 15-297
        • Research Site
      • Bydgoszcz, Poland, 85 168
        • Research Site
      • Koscian, Poland, 64-000
        • Research Site
      • Kraków, Poland, 31-011
        • Research Site
      • Lublin, Poland, 20-607
        • Research Site
      • Nadarzyn, Poland, 05-830
        • Research Site
      • Starachowice, Poland, 27-200
        • Research Site
      • Szczecin, Poland, 71-252
        • Research Site
      • Ustron, Poland, 43-450
        • Research Site
      • Warszawa, Poland, 02-118
        • Research Site
      • Brasov, Romania, 500283
        • Research Site
      • Bucuresti, Romania, 011172
        • Research Site
      • Cluj Napoca, Romania, 400006
        • Research Site
      • Galati, Romania, 800578
        • Research Site
      • Targu Mures, Romania, 540136
        • Research Site
      • Smolensk, Russian Federation, 214015
        • Research Site
      • Tolyatti, Russian Federation, 445039
        • Research Site
      • Vladimir, Russian Federation, 600023
        • Research Site
      • Yaroslavl, Russian Federation, 150003
        • Research Site
      • Cape Town, South Africa, 7500
        • Research Site
      • Johannesburg, South Africa, 2021
        • Research Site
      • Stellenbosch, South Africa, 7600
        • Research Site
      • Barcelona, Spain, 08035
        • Research Site
      • Getafe, Spain, 28905
        • Research Site
      • Mérida, Spain, 06800
        • Research Site
      • Servilla, Spain, 41014
        • Research Site
      • Vigo, Spain, 36200
        • Research Site
      • Kaohsiung, Taiwan, 83301
        • Research Site
      • Taichung, Taiwan, 40705
        • Research Site
      • Taipei, Taiwan, 10002
        • Research Site
      • Kyiv, Ukraine, 01601
        • Research Site
      • Kyiv, Ukraine, 03680
        • Research Site
      • Lviv, Ukraine, 79011
        • Research Site
      • Ternopil, Ukraine, 46001
        • Research Site
      • Uzhhorod, Ukraine, 88018
        • Research Site
      • Vinnytsia, Ukraine, 21018
        • Research Site
      • Zaporizhzhia, Ukraine, 69600
        • Research Site
      • Doncaster, United Kingdom, DN2 5LT
        • Research Site
      • Leeds, United Kingdom, LS7 4SA
        • Research Site
      • London, United Kingdom, SE1 9RT
        • Research Site
      • Manchester, United Kingdom, M13 9WL
        • Research Site
    • Alabama
      • Birmingham, Alabama, United States, 35294-3280
        • Research Site
    • California
      • El Cajon, California, United States, 92020
        • Research Site
      • Hemet, California, United States, 92543
        • Research Site
      • La Jolla, California, United States, 92037
        • Research Site
      • Los Alamitos, California, United States, 90720
        • Research Site
      • Los Angeles, California, United States, 90024
        • Research Site
      • San Leandro, California, United States, 94578
        • Research Site
      • Thousand Oaks, California, United States, 91360
        • Research Site
      • Upland, California, United States, 91786
        • Research Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Research Site
      • Denver, Colorado, United States, 80230
        • Research Site
    • Connecticut
      • Bridgeport, Connecticut, United States, 06606
        • Research Site
    • Florida
      • Brandon, Florida, United States, 33511
        • Research Site
      • DeBary, Florida, United States, 32713
        • Research Site
      • Miami, Florida, United States, 33136
        • Research Site
      • Miami, Florida, United States, 33180
        • Research Site
      • Ormond Beach, Florida, United States, 32174
        • Research Site
      • Tampa, Florida, United States, 33614
        • Research Site
      • Vero Beach, Florida, United States, 32960
        • Research Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Research Site
      • Decatur, Georgia, United States, 30033
        • Research Site
      • Lawrenceville, Georgia, United States, 30046
        • Research Site
      • Marietta, Georgia, United States, 30060
        • Research Site
    • Idaho
      • Boise, Idaho, United States, 83702
        • Research Site
      • Idaho Falls, Idaho, United States, 83404
        • Research Site
    • Maryland
      • Cumberland, Maryland, United States, 21502
        • Research Site
      • Hagerstown, Maryland, United States, 21740
        • Research Site
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Research Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455-0341
        • Research Site
    • New Hampshire
      • Nashua, New Hampshire, United States, 03060
        • Research Site
    • New Jersey
      • Freehold, New Jersey, United States, 07728
        • Research Site
    • New Mexico
      • Las Cruces, New Mexico, United States, 88011
        • Research Site
    • New York
      • Brooklyn, New York, United States, 11201
        • Research Site
      • Great Neck, New York, United States, 11021
        • Research Site
      • New Hyde Park, New York, United States, 11042
        • Research Site
      • New York, New York, United States, 10016
        • Research Site
      • New York, New York, United States, 10021
        • Research Site
      • New York, New York, United States, 10032
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28277
        • Research Site
      • Charlotte, North Carolina, United States, 28210
        • Research Site
      • Greenville, North Carolina, United States, 27834
        • Research Site
      • Raleigh, North Carolina, United States, 27617
        • Research Site
    • Ohio
      • Middleburg Heights, Ohio, United States, 44130
        • Research Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Research Site
      • Oklahoma City, Oklahoma, United States, 73102
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Research Site
      • Pittsburgh, Pennsylvania, United States, 15213
        • Research Site
      • Reading, Pennsylvania, United States, 19610
        • Research Site
    • South Carolina
      • North Charleston, South Carolina, United States, 29406
        • Research Site
    • Tennessee
      • Memphis, Tennessee, United States, 38119
        • Research Site
      • Memphis, Tennessee, United States, 38104
        • Research Site
    • Texas
      • Amarillo, Texas, United States, 79124
        • Research Site
      • Austin, Texas, United States, 78745
        • Research Site
      • Austin, Texas, United States, 78726
        • Research Site
      • Dallas, Texas, United States, 75231
        • Research Site
      • Houston, Texas, United States, 77074
        • Research Site
      • Houston, Texas, United States, 77034
        • Research Site
      • Houston, Texas, United States, 77004
        • Research Site
      • Mesquite, Texas, United States, 75150
        • Research Site
      • Stafford, Texas, United States, 77477
        • Research Site
    • Washington
      • Spokane, Washington, United States, 99204
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53217
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Subjects who have qualified for and received investigational product (anifrolumab or placebo) and completed the treatment period in Studies D3461C00004 or D3461C00005 (through Week 52)
  2. Adequate peripheral venous access
  3. Females with an intact cervix should have documentation of a Pap smear with no documented malignancy within 90 days before Day 1/Visit 1 or 30 days following Day 1/Visit 1. Since access to a Pap smear may vary by country, the Sponsor recommends that local guidelines for obtaining Pap smears in subjects who have received immunomodulators or immunosuppressive treatment be followed.
  4. Meets the following TB criteria:

    1. 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
    2. 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
    3. 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)
    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
  5. In the opinion of the Investigator, subject must be able to comprehend the ICF and all protocol related assessments

Exclusion Criteria:

  1. Receipt of any of the following within the last 60 days:

    1. Azathioprine >200 mg/day
    2. Mycophenolate mofetil >2.0 g/day /mycophenolic acid >1.44 g/day
    3. Oral, subcutaneous, or intramuscular methotrexate >25 mg/week
    4. Mizoribine >150 mg/day
  2. Receipt of any investigational product (small molecule or biologic agent other than anifrolumab) within 4 weeks or 5 half-lives prior to Day 1/Visit 1, whichever is greater
  3. Receipt of any of the following:

    1. 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)
    2. Bacillus Calmette-Guerin (BCG) vaccine between the end of Studies D3461C00004 or D3461C00005 and Day 1/Visit 1
  4. Active severe SLE-driven renal or neuropsychiatric disease
  5. Any underlying condition that predisposes the subject to infection, including history of/current human immunodeficiency virus (HIV) infection
  6. Subjects with Hepatitis B core antibody (HBcAb) positivity at enrolment of Studies D3461C00004 or D3461C00005 will be tested every 3 months for Hepatitis B virus (HBV) DNA. To remain eligible in the LTE study, subject HBV DNA levels must remain below the lower limit of quantitation as per the central laboratory.
  7. Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years of Day 1/Visit 1

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses
Experimental: Anifrolumab
Anifrolumab IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses

What is the study measuring?

Primary Outcome Measures

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

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)
Time Frame: Up to a maximum of 1114 days

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Principal Investigator: Kenneth Kalunian, MD, University of California, San Diego
  • Study Director: Raj Tummala, MD, AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2016

Primary Completion (Actual)

December 21, 2021

Study Completion (Actual)

December 21, 2021

Study Registration Dates

First Submitted

June 6, 2016

First Submitted That Met QC Criteria

June 6, 2016

First Posted (Estimate)

June 9, 2016

Study Record Updates

Last Update Posted (Estimate)

January 13, 2023

Last Update Submitted That Met QC Criteria

December 19, 2022

Last Verified

December 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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