Clinical trial NCT02794285: Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Active Systemic Lupus Erythematosus
Keywords: Lupus Erythematosus, Systemic Autoimmune Diseases, Connective Tissue Diseases,Immune System Diseases
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2016-06-09
Enrollment: 559
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Exposure-adjusted Incidence Rates (EAIRs) of Adverse Events of Special Interest (AESIs)
timeFrame: Up to a maximum of 1114 days
measure: EAIRs of Serious Adverse Events (SAEs)
timeFrame: Up to a maximum of 1114 days
Secondary outcomes:
Other outcomes:
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country: Poland
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city: Szczecin
country: Poland
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city: Ustron
country: Poland
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city: Warszawa
country: Poland
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city: Brasov
country: Romania
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city: Bucuresti
country: Romania
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city: Cluj Napoca
country: Romania
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city: Galati
country: Romania
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city: Targu Mures
country: Romania
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city: Smolensk
country: Russian Federation
facility: Research Site
city: Tolyatti
country: Russian Federation
facility: Research Site
city: Vladimir
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
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city: Stellenbosch
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
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city: Getafe
country: Spain
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city: Mérida
country: Spain
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country: Spain
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city: Vigo
country: Spain
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city: Kaohsiung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taipei
country: Taiwan
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city: Kyiv
country: Ukraine
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city: Kyiv
country: Ukraine
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country: Ukraine
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city: Ternopil
country: Ukraine
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city: Uzhhorod
country: Ukraine
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city: Vinnytsia
country: Ukraine
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city: Zaporizhzhia
country: Ukraine
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city: Doncaster
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: University of California, San Diego
name: Kenneth Kalunian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Raj Tummala, MD
role: STUDY_DIRECTOR
References:
citation: Kalunian 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.