Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus
- Conditions
- Systemic Lupus Erythematosus
- Interventions
- Drug: Placebo
- Registration Number
- NCT04877691
- Lead Sponsor
- AstraZeneca
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 367
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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
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To be eligible a patient must have SLEDAI-2K ≥ 6 points and "Clinical" SLEDAI-2K score ≥4 points at screening
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BILAG2004 with at least 1 of the following:
- BILAG2004 level A disease in ≥ 1 organ system
- BILAG2004 level B disease in ≥ 2 organ systems
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Physician's Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 VAS at Screening
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Antinuclear antibody, and/or Anti-dsDNA and/oranti-Smith positive at Screening,
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Must be on stable background standard therapy with DMARD, glucocorticoids or anti-malarials alone or in combinations.
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Active severe or unstable neuropsychiatric SLE
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Active severe SLE-driven renal disease
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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.
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History of recurrent infection requiring hospitalization and IV antibiotics (eg, 3 or more of the same type of infection over the previous 52 weeks).
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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.
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At Screening, confirmed positive test for hepatitis B serology and positive test for hepatitis C antibody
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Any severe case herpes zoster infection at any time prior to Week 0 (Day 1),
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Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization.
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History of cancer, apart from:
- Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1)
- Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Solution for injection in aPFS Anifrolumab Medi-546 Solution for injection in aPFS
- Primary Outcome Measures
Name Time Method British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response At week 52 BICLA response is a composite binary endpoint whereby responders are defined by meeting all of the following criteria:
* Improvement from baseline in disease activity as measured by BILAG-2004. Improvement is defined as a reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D and no BILAG-2004 worsening in other organ systems, where worsening is defined as ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG 2004 B.
* No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of \> 0 points in SLEDAI-2K.
* No worsening from baseline in the patient's lupus disease activity, where worsening is defined as an increase ≥ 0.30 points on a 3-point PGA VAS.
- Secondary Outcome Measures
Name Time Method SRI4 At week 52 Proportion of patients achieving a SRI of ≥ 4 (SRI\[4\]) response at Week 52, defined by meeting all of the following criteria:
Reduction from baseline of ≥ 4 points in the SLEDAI-2K No new organ systems affected as defined by 1 or more BILAG-2004 A or 2 or more BILAG 2004 B items compared to baseline using BILAG-2004 No worsening from baseline in the patients' lupus disease activity, where worsening is defined by an increase ≥ 0.30 points on a 3-point PGA VAS.BICLA response with maintained low (or reduced) use of oral corticosteroid (OCS) At week 52 Response is defined by being a BICLA responder at Week 52 and having maintained low (or reduced) OCS use through Week 52. Maintained OCS use is defined as follows:
* If baseline OCS ≥ 10 mg/day an OCS dose of ≤ 7.5 mg/day prednisone or equivalent must be achieved by Week 40 and an OCS dose ≤ 7.5 mg/day prednisone or equivalent must be maintained from Week 40 to Week 52.
* If baseline OCS \< 10 mg/day, OCS dose at Week 40 must be less than or equal to OCS dose at baseline, with no increase from Week 40 OCS dose between Week 40 and Week 52.Time to first BICLA response sustained through Week 52 Baseline through to Week 52 Time from first dose to first BICLA response that is consecutively maintained through Week 52
Time to flare Baseline through to Week 52 Flare defined as either 1 or more BILAG 2004 A or 2 or more BILAG 2004 B compared to previous visit
Maintained oral corticosteroid (OCS) reduction among patients with baseline OCS ≥10 mg/day. At week 52 Achieving maintained OCS reduction through Week 52 is defined by meeting all of the following criteria:
* Achieve an OCS dose of ≤ 7.5 mg/day prednisone or equivalent by Week 40
* Maintain an OCS dose ≤ 7.5 mg/day prednisone or equivalent from Week 40 to Week 52
* No discontinuation of investigational product
* No use of restricted medications beyond the protocol allowed threshold before assessmentAnnualized flare rate Baseline through to Week 52 Flare defined as either 1 or more BILAG 2004 or 2 or more BILAG2004 B compared to previous visit
Trial Locations
- Locations (1)
Research Site
🇬🇧London, United Kingdom