Clinical trial NCT04877691: Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus
Official title: A Multicentre, Randomised, Double-Blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Keywords: Systemic Lupus Erythematosuss Anifrolumab, Adult patients, BICLA, glucocorticoids, Immunosuppressant(s), sub-cutaneous
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2021-05-07
Enrollment: 367
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 evaluating the efficacy and safety of SC antifrolumab in adult patients with moderate -to-severe SLE despite receiving standard therapy

Detailed description: This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of a subcutaneous treatment regimen of anifrolumab versus placebo in participants with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. Participants must be taking either 1 or any combination of the following: oral glucocorticoids, antimalarial, and/or immunosuppressants. The study will be performed in adult participants of 18 to 70 years of age.

Approximately 360 participants receiving SOC treatment will be randomised in a 1:1 ratio to receive a fixed subcutaneous dose of anifrolumab or placebo administered once weekly via an accessorized prefilled syringe and with the primary endpoint evaluated at Week 52. Subjects who complete Week 52 may enter into open-label extension (OLE). All patients who enter the OLE Period will receive a fixed subcutaneous dose of anifrolumab for up to 52 weeks. Study intervention will be administered SC via an accessorised prefilled syringe (aPFS).

Eligibility criteria: Inclusion Criteria:

1. Patients who have a diagnosis of pediatric or adult SLE according to the ACR 1997 revised criteria for ≥ 24 weeks prior to signing the ICF
2. To be eligible a patient must have SLEDAI-2K ≥ 6 points and "Clinical" SLEDAI-2K score ≥4 points at screening
3. BILAG2004 with at least 1 of the following:

   1. BILAG2004 level A disease in ≥ 1 organ system
   2. BILAG2004 level B disease in ≥ 2 organ systems
4. Physician's Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 VAS at Screening
5. Antinuclear antibody, and/or Anti-dsDNA and/oranti-Smith positive at Screening,
6. Must be on stable background standard therapy with DMARD, glucocorticoids or anti-malarials alone or in combinations.

   Exclusion Criteria:
7. Active severe or unstable neuropsychiatric SLE
8. Active severe SLE-driven renal disease
9. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF.
10. History of recurrent infection requiring hospitalization and IV antibiotics (eg, 3 or more of the same type of infection over the previous 52 weeks).
11. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the patient to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at Screening.
12. At Screening, confirmed positive test for hepatitis B serology and positive test for hepatitis C antibody
13. Any severe case herpes zoster infection at any time prior to Week 0 (Day 1),
14. Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization.
15. History of cancer, apart from:

    1. Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1)
    2. Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1).

Primary outcomes:
measure: British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response
timeFrame: At week 52
Secondary outcomes:
measure: Time to first BICLA response sustained through Week 52
timeFrame: Baseline through to Week 52
measure: BICLA response with maintained low (or reduced) use of oral corticosteroid (OCS)
timeFrame: At week 52
measure: Time to flare
timeFrame: Baseline through to Week 52
measure: Maintained oral corticosteroid (OCS) reduction among patients with baseline OCS ≥10 mg/day.
timeFrame: At week 52
measure: Annualized flare rate
timeFrame: Baseline through to Week 52
measure: SRI4
timeFrame: At week 52
Other outcomes:
measure: Adverse Event Overview
timeFrame: Up to 2 years 4 months
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country: Poland
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country: Thailand
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city: Rachathewi
country: Thailand
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city: Kyiv
country: Ukraine
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city: Kyiv
country: Ukraine
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city: Kyiv
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country: Ukraine
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country: Ukraine
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city: Vinnytsia
country: Ukraine
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country: Ukraine
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city: Doncaster
country: United Kingdom
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city: Leeds
country: United Kingdom
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city: London
country: United Kingdom
facility: Research Site
Study officials:
References: