A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 3 Study Evaluating the Efficacy and Safety of Two Doses of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus

AstraZeneca1 site in 1 country460 target enrollmentJune 9, 2015

ConditionsActive Systemic Lupus Erythematosus

InterventionsAnifrolumab Placebo

DrugsPlacebo

Overview

Phase: Phase 3
Intervention: Anifrolumab
Conditions: Active Systemic Lupus Erythematosus
Sponsor: AstraZeneca
Enrollment: 460
Locations: 1
Primary Endpoint: Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules)
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of two doses of anifrolumab versus placebo in adult subjects with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE).

Detailed Description

This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of an intravenous treatment regimen of two doses of anifrolumab versus placebo in subjects with moderately to severely active, autoantibody-positive systemic lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. The study will be performed in adult subjects aged 18 to 70 years of age.

Registry

clinicaltrials.gov

Start Date

June 9, 2015

End Date

July 17, 2018

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Aged 18 through 70 years at the time of screening
•Diagnosis of paediatric or adult SLE with a diagnosis of SLE according to the ACR 1982 revised criteria ≥24 weeks prior to signing the Informed Consent form (ICF)
•Currently receiving at least 1 of the following:
•Where prednisone is the single standard of care medication (ie, the subject is not concurrently receiving any medication listed in inclusion criterion 3(c)), a dose of oral prednisone ≥7.5 mg/day but ≤40 mg/day (or prednisone equivalent) for a minimum of 8 weeks prior to Day
•In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation.
•Where prednisone is not the single standard of care medication (ie, the subject is concurrently receiving at least one medication listed in inclusion criterion 3(c)), a dose of oral prednisone (≤40 mg/day) (or prednisone equivalent) for a minimum of 2 weeks prior to signing of the ICF. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation.
•Any of the following medications administered for a minimum of 12 weeks prior to signing the informed consent, and at a stable dose for a minimum of 8 weeks prior to signing the informed consent through Day 1:
•(i) Azathioprine ≤200 mg/day (ii) Antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week (v) Mizoribine ≤150 mg/day
•Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at least 1 of which must be:
•Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay (IFA) at the central laboratory with titre ≥1:80; OR

Exclusion Criteria

•Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater
•Receipt of any of the following:
•(a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1
•History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome.
•Active severe or unstable neuropsychiatric SLE
•Active severe SLE-driven renal disease
•Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE or SSc.
•History of, or current, inflammatory joint or skin disease other than SLE
•History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the ICF
•Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation

Arms & Interventions

Anifrolumab - higher dose

Anifrolumab

Intervention: Anifrolumab

Placebo

Intervention: Placebo

Anifrolumab - lower dose

Anifrolumab

Intervention: Anifrolumab

Outcomes

Primary Outcomes

Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index ≥4 (SRI[4]) at Week 52 (Original Analysis With Restricted Medication Rules)

Time Frame: Week 52

SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) No new organ systems affected, defined by 1 or more British Isles Lupus Assessment Group (BILAG-2004) A or 2 or more BILAG-2004 B items No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.

Secondary Outcomes

Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 at Week 52 in the Interferon (IFN) Test-High Sub-Group (Original Analysis With Restricted Medication Rules)(Week 52)
Number of Participants Who Achieved a Systemic Lupus Erythematosus (SLE) Responder Index of ≥4 (SRI[4]) at Week 24 (Original Analysis With Restricted Medication Rules)(Week 24)
Annualized Flare Rate(Baseline to Week 52)
Number of Participants Who Achieved and Maintained an Oral Corticosteroid (OCS) Dose of ≤7.5 mg/Day in the Sub-group of Participants With Baseline OCS ≥10 mg/Day (Original Analysis With Restricted Medication Rules)(Week 52)
Number of Participants With a ≥50% Reduction in CLASI Activity Score at Week 12 in the Sub-group of Participants With Baseline CLASI Activity Score ≥10 (Original Analysis With Restricted Medication Rules)(Week 12)
Number of Participants Who Met the Criteria for British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response (Original Analysis With Restricted Medication Rules)(Week 52)
Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Scores(Baseline to Week 52)
Number of Participants With Mild To Moderate Lupus Flare Evaluated by Modified Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI Flare Index(Baseline to End of Trial (Maximum of 60 weeks))
Number of Participants With Markedly Abnormal Laboratory Tests(Baseline to End of Trial (Maximum of 60 weeks))
Number of Participants With Markedly Abnormal Vital Signs(Baseline to End of Trial (Maximum of 60 weeks))
Change From Baseline in Personal Health Questionnaire Depression Scale-8 (PHQ-8) Score(Baseline to Week 52)
Number of Participants Reporting One or More Adverse Events (AE)(Baseline to End of Trial (Maximum of 60 weeks))
Number of Participants With Markedly Abnormal Physical Examinations(Baseline to End of Trial (Maximum of 60 weeks))
Number of Participants Reporting One or More Adverse Events of Special Interest (AESI)(Baseline to End of Trial (Maximum of 60 weeks))
Number of Participants With Suicidal Ideation or Behaviour Assessed Via the Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline to Week 52)