Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Medi-546
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 To be eligible a patient must have SLEDAI-2K ≥ 6 points and Clinical SLEDAI-2K score ≥4 points at screening BILAG2004 with at least 1 of the following: BILAG2004 level A disease in ≥ 1 organ system BILAG2004 level B disease in ≥ 2 organ systems Physician's Global Assessment (PGA) score ≥ 1.0 on a 0 to 3 VAS at Screening Antinuclear antibody, and/or Anti-dsDNA and/oranti-Smith positive at Screening, Must be on stable background standard therapy with DMARD, glucocorticoids or anti-malarials alone or in combinations. Exclusion Criteria: Active severe or unstable neuropsychiatric SLE Active severe SLE-driven renal disease 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. History of recurrent infection requiring hospitalization and IV antibiotics (eg, 3 or more of the same type of infection over the previous 52 weeks). 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. At Screening, confirmed positive test for hepatitis B serology and positive test for hepatitis C antibody Any severe case herpes zoster infection at any time prior to Week 0 (Day 1), Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization. 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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anifrolumab<br>Solution for injection in aPFS | Drug: Medi-546<br>* Patients will have IP administered or will self-administer IP under supervision by site staff at Week 0 and Week 1 and, for patients participating in the OLE period, at Week 52. For weekly doses coinciding with subsequent on-site visits, patients will also have IP administered or will self-administer IP under supervision by site staff, and in addition will receive a set of kits (including back-up kits) for at-home administration.<br>|
| Placebo Comparator: Placebo<br>Solution for injection in aPFS | Drug: Placebo<br>* Solution for injection in aPFS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response | 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. | At week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first BICLA response sustained through Week 52 | Time from first dose to first BICLA response that is consecutively maintained through Week 52 | Baseline through to Week 52 | 
| BICLA response with maintained low (or reduced) use of oral corticosteroid (OCS) | 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. | At week 52 | 
| Time to flare | Flare defined as either 1 or more BILAG 2004 A or 2 or more BILAG 2004 B compared to previous visit | Baseline through to Week 52 | 
| Maintained oral corticosteroid (OCS) reduction among patients with baseline OCS ≥10 mg/day. | 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 assessment | At week 52 | 
| Annualized flare rate | Flare defined as either 1 or more BILAG 2004 or 2 or more BILAG2004 B compared to previous visit | Baseline through to Week 52 | 
| SRI4 | 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. | At week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosuss Anifrolumab, Adult patients, BICLA, glucocorticoids, Immunosuppressant(s), sub-cutaneous