Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus

Active Systemic Lupus Erythematosus Clinical Trial

— TULIP SLE LTE  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02794285
• Other study ID #: D3461C00009
• Status: Completed
• Phase: Phase 3
• Start date: June 30, 2016
• Est. completion date: December 21, 2021

Study information

• Verified date: December 2022
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 559
• Est. completion date: December 21, 2021
• Est. primary completion date: December 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Active Systemic Lupus Erythematosus
• Lupus Erythematosus, Systemic

Intervention

Biological:
• Anifrolumab
Anifrolumab IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses

Drug:
• Placebo
Placebo IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses

Locations

Country	Name	City	State
Argentina	Research Site	Mendoza
Argentina	Research Site	Quilmes
Argentina	Research Site	San Miguel de Tucuman
Australia	Research Site	Fitzroy
Australia	Research Site	Kogarah
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Rimouski	Quebec
Chile	Research Site	Osorno
Chile	Research Site	Santiago
Chile	Research Site	Vina del Mar
Colombia	Research Site	Armenia
Colombia	Research Site	Barranquilla
Colombia	Research Site	Medellín
France	Research Site	Bordeaux
France	Research Site	Lille
France	Research Site	Montpellier CEDEX 5
France	Research Site	Paris Cedex 13
France	Research Site	Paris cedex 14
France	Research Site	Pessac
Germany	Research Site	Berlin
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Hamburg
Germany	Research Site	Jena
Germany	Research Site	Kirchheim
Germany	Research Site	Mainz Am Rhein
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Szeged
Hungary	Research Site	Zalaegerszeg
Israel	Research Site	Haifa
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Saba
Israel	Research Site	Tel Aviv
Japan	Research Site	Chiba-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Kitakyushu-shi
Japan	Research Site	Kurashiki-shi
Japan	Research Site	Meguro-ku
Japan	Research Site	Meguro-ku
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Omura-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sasebo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjuku-ku
Korea, Republic of	Research Site	Daejeon
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Jeju-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Klaipeda
Mexico	Research Site	Chihuahua
Mexico	Research Site	Leon
Mexico	Research Site	Mérida
Mexico	Research Site	Mexico
Mexico	Research Site	Mexico D.F.
Mexico	Research Site	San Luis Potosí
Peru	Research Site	Arequipa
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Koscian
Poland	Research Site	Kraków
Poland	Research Site	Lublin
Poland	Research Site	Nadarzyn
Poland	Research Site	Starachowice
Poland	Research Site	Szczecin
Poland	Research Site	Ustron
Poland	Research Site	Warszawa
Romania	Research Site	Brasov
Romania	Research Site	Bucuresti
Romania	Research Site	Cluj Napoca
Romania	Research Site	Galati
Romania	Research Site	Targu Mures
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	Tolyatti
Russian Federation	Research Site	Vladimir
Russian Federation	Research Site	Yaroslavl
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Stellenbosch
Spain	Research Site	Barcelona
Spain	Research Site	Getafe
Spain	Research Site	Mérida
Spain	Research Site	Servilla
Spain	Research Site	Vigo
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Ternopil
Ukraine	Research Site	Uzhhorod
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhia
United Kingdom	Research Site	Doncaster
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Amarillo	Texas
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boise	Idaho
United States	Research Site	Brandon	Florida
United States	Research Site	Bridgeport	Connecticut
United States	Research Site	Brooklyn	New York
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cumberland	Maryland
United States	Research Site	Dallas	Texas
United States	Research Site	DeBary	Florida
United States	Research Site	Decatur	Georgia
United States	Research Site	Denver	Colorado
United States	Research Site	El Cajon	California
United States	Research Site	Freehold	New Jersey
United States	Research Site	Grand Rapids	Michigan
United States	Research Site	Great Neck	New York
United States	Research Site	Greenville	North Carolina
United States	Research Site	Hagerstown	Maryland
United States	Research Site	Hemet	California
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Idaho Falls	Idaho
United States	Research Site	La Jolla	California
United States	Research Site	Las Cruces	New Mexico
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Los Alamitos	California
United States	Research Site	Los Angeles	California
United States	Research Site	Marietta	Georgia
United States	Research Site	Memphis	Tennessee
United States	Research Site	Memphis	Tennessee
United States	Research Site	Mesquite	Texas
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Middleburg Heights	Ohio
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashua	New Hampshire
United States	Research Site	New Hyde Park	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	North Charleston	South Carolina
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Reading	Pennsylvania
United States	Research Site	San Leandro	California
United States	Research Site	Spokane	Washington
United States	Research Site	Stafford	Texas
United States	Research Site	Tampa	Florida
United States	Research Site	Thousand Oaks	California
United States	Research Site	Upland	California
United States	Research Site	Vero Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	PRA Health Sciences

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bulgaria,  Canada,  Chile,  Colombia,  France,  Germany,  Hungary,  Israel,  Japan,  Korea, Republic of,  Lithuania,  Mexico,  Peru,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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

External Links

•   CSR Synopsis