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Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02446912
First Posted: May 18, 2015
Last Update Posted: September 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
AstraZeneca
  Purpose
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).

Condition Intervention Phase
Active Systemic Lupus Erythematosus Biological: Anifrolumab Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • To evaluate the effect of anifrolumab compared to placebo on disease activity as measured by the difference in the proportion of subjects who achieve an SLE Responder Index of ≥4 (SRI[4]) at Week 52 [ Time Frame: Week 52 ]

    Composite endpoint SRI(4), defined by the following criteria:

    • Reduction from baseline of ≥4 points in the SLEDAI-2K and
    • No new organ system affected as defined by 1 or more British Isles Lupus Assessment Group (BILAG) 2004 A or 2 or more BILAG-2004 B items compared to baseline using BILAG-2004 and
    • No worsening from baseline in subjects' lupus disease activity defined by an increase ≥0.30 points on a 3 point Physician's Global Assessment (PGA) visual analogue scale (VAS) and
    • No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessment


Secondary Outcome Measures:
  • To evaluate the effect of anifrolumab compared to placebo on the proportion of subjects with SRI(4) at Week 52 in the IFN test-high sub-group [ Time Frame: Week 52 ]

    Composite endpoint SRI(4), defined by the following criteria:

    • Reduction from baseline of ≥4 points in the SLEDAI-2K and
    • No new organ system affected as defined by 1 or more British Isles Lupus Assessment Group (BILAG) 2004 A or 2 or more BILAG-2004 B items compared to baseline using BILAG-2004 and
    • No worsening from baseline in subjects' lupus disease activity defined by an increase ≥0.30 points on a 3 point Physician's Global Assessment (PGA) visual analogue scale (VAS) and
    • No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessment

  • To evaluate the effect of anifrolumab compared to placebo on the the proportion of subjects who achieve an OCS dose ≤7.5 mg/day at Week 40, which is maintained through Week 52 in the sub-group of subjects with baseline OCS ≥10 mg/day [ Time Frame: Week 52 ]

    Maintained OCS reduction defined by the following criteria:

    • Achieve an OCS dose of ≤7.5 mg/day prednisone or equivalent by Week 40 and
    • Maintain an OCS dose ≤7.5 mg/day prednisone or equivalent from Week 40 to Week 52 and
    • No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessment

  • To evaluate the effect of anifrolumab compared to placebo on the proportion of subjects with a ≥50% reduction in CLASI activity score at Week 12 in the sub-group of subjects with baseline CLASI activity score ≥10 [ Time Frame: Week 12 ]

    50% reduction in CLASI activity score compared to baseline defined by the following criteria:

    • Achieve ≥50% reduction of CLASI activity score at Week 12 compared to baseline and
    • No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessment

  • To evaluate the effect of anifrolumab compared to placebo on The proportion of patients with SRI(4) at Week 24 [ Time Frame: Week 24 ]

    Composite endpoint SRI(4), defined by the following criteria:

    • Reduction from baseline of ≥4 points in the SLEDAI-2K and
    • No new organ system affected as defined by 1 or more British Isles Lupus Assessment Group (BILAG) 2004 A or 2 or more BILAG-2004 B items compared to baseline using BILAG-2004 and
    • No worsening from baseline in subjects' lupus disease activity defined by an increase ≥0.30 points on a 3 point Physician's Global Assessment (PGA) visual analogue scale (VAS) and
    • No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessment

  • To evaluate the effect of anifrolumab compared to placebo on the annualised flare rate through 52 weeks [ Time Frame: Week 0 - 52 ]
    Annualised flare rate with flare defined as either 1 or more new BILAG 2004 A or 2 or more new BILAG 2004 B items compared to the previous visit

  • To evaluate the effect of anifrolumab compared to placebo on disease activity as measured by the difference in the proportion of subjects who achieve SRI(4) at Week 52 [ Time Frame: Week 52 ]

    Composite endpoint SRI(4), defined by the following criteria:

    • Reduction from baseline of ≥4 points in the SLEDAI-2K and
    • No new organ system affected as defined by 1 or more British Isles Lupus Assessment Group (BILAG) 2004 A or 2 or more BILAG-2004 B items compared to baseline using BILAG-2004 and
    • No worsening from baseline in subjects' lupus disease activity defined by an increase ≥0.30 points on a 3 point Physician's Global Assessment (PGA) visual analogue scale (VAS) and
    • No discontinuation of investigational product or use of restricted medications beyond the protocol allowed threshold before assessment

  • To evaluate the safety and tolerability of anifrolumab [ Time Frame: Week 0-52 ]
    Adverse events (AEs) (including adverse events of special interest [AESIs]), vital signs, physical examination, 12-lead electrocardiograms, modified SLEDAI Flare Index based flares, clinical laboratory tests (haematology, clinical chemistry, urinalysis), Columbia Suicide Severity Rating Scale, and Personal Health Questionnaire Depression Scale-8


Enrollment: 460
Actual Study Start Date: June 9, 2015
Estimated Study Completion Date: July 13, 2018
Estimated Primary Completion Date: July 13, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anifrolumab - higher dose
Anifrolumab
Biological: Anifrolumab
Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo IV administration every 4 weeks from Week 0 to Week 48
Experimental: Anifrolumab - lower dose
Anifrolumab
Biological: Anifrolumab
Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses

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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged 18 through 70 years at the time of screening
  2. 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)
  3. Currently receiving at least 1 of the following:

    1. 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 1. 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.
    2. 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.
    3. 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

  4. Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at least 1 of which must be:

    1. Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay (IFA) at the central laboratory with titre ≥1:80; OR
    2. Anti-dsDNA antibodies at screening elevated to above normal (including indeterminante), as per the central laboratory; OR
    3. Anti-Smith (anti-Sm) antibody at screening elevated to above normal as per the central laboratory.
  5. At Screening, Disease Activity Adjudication Group confirmation of:

    SLEDAI-2K Criteria: SLEDAI-2K score ≥6 points and "Clinical" SLEDAI-2K score ≥4 points. The "Clinical" SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures.

  6. Must not have active or latent TB on either chest radiograph or by quantiferon gold test
  7. Day 1 "Clinical" SLEDAI-2K score ≥4 points
  8. OCS dose stable for at least 2 weeks prior to randomisation
  9. Stable SLE SOC treatment at the time of randomisation
  10. Women of child-bearing potential must have a negative serum β-hCG test and negative urine pregnancy test at randomisation (Day 1) prior to administration of investigational product

Exclusion Criteria:

  1. 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
  2. Receipt of any of the following:

    (a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1

  3. History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome.
  4. Active severe or unstable neuropsychiatric SLE
  5. Active severe SLE-driven renal disease
  6. Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE or SSc.
  7. History of, or current, inflammatory joint or skin disease other than SLE
  8. 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
  9. 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
  10. Confirmed positive test for hepatitis B or hepatitis C
  11. Any severe herpes infection at any time prior to Week 0 (Day 1)
  12. Opportunistic infection requiring hospitalisation or intravenous antimicrobial treatment within 3 years prior to randomization
  13. History of cancer, apart from:

    1. Squamous or basal cell carcinoma of the skin that has been successfully treated
    2. Cervical cancer in situ that has been successfully treated
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02446912


  Show 144 Study Locations
Sponsors and Collaborators
AstraZeneca
PRA Health Sciences
Investigators
Study Director: Herbert Hutman, MD Medical Science Director
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02446912     History of Changes
Other Study ID Numbers: D3461C00005
First Submitted: May 14, 2015
First Posted: May 18, 2015
Last Update Posted: September 20, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Active Systemic Lupus Erythematosus

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs