A study to evaluate the efficacy and safety of two doses of Anifrolumab compared to placebo in adult patients with Active Systemic Lupus Erythematosus
- Conditions
- Systemic Lupus ErythematosusMedDRA version: 20.0Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2014-004633-96-PL
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 457
1. Aged 18 through 70 years at the time of screening
2. Completion of all screening procedures needed to determine subject eligibility and stratification within 30 days after signing the Informed Consent Form (ICF)
3. Diagnosis of paediatric or adult SLE with a diagnosis of SLE according
to the ACR 1982 revised criteria =24 weeks prior to signing the ICF
4. Currently receiving at least 1 of the following:
(a) Where prednisone is the single standard of care medication, 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.
(b) Where prednisone is not the single standard of care medication, 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.
(c) 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
5. Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for
SLE, at least 1 of which must be:
(a) Positive antinuclear antibody (ANA) test at screening by
immunofluorescent assay (IFA) at the central laboratory with titre =
1:80; OR
(b) Anti-dsDNA antibodies at screening elevated to above normal
(including indeterminate), as per the central laboratory; OR
(c) Anti-Smith (anti-Sm) antibody at screening elevated to above normal
as per the central laboratory
6. 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.
7. Meets all of the following TB criteria:
(i) No history of active TB prior to any Screening visit
(ii) No history of latent TB prior to initial Screening visit, with the
exception of latent TB with documented completion of appropriate
treatment. Subjects with no history of latent TB prior to the initial
Screening visit, but who are diagnosed with latent TB during screening,
may be considered eligible if appropriate treatment is initiated prior to
randomisation. Such subjects may be re-screened if necessary to allow
for local guidelines on latent TB treatment initiation.
8. Day 1 Clinical SLEDAI-2K score =4 points
9. OCS dose stable for at least 2 weeks prior to randomisation
10. Stable SLE SOC treatment at the time of randomisation
11. Women of child-bearing potential must have a negative serum ß-hCG
test at screening and a negative urine pregnancy test at randomisation
(Day 1), prior to administration of investigational product
12. In the opinion of the Investigator, must be able to comprehend the
ICF and all protocol related assessments, such that the patient can
complete all study required documents,
1. Receipt of any of the following:
(a) Where prednisone is the single standard of care medication, any new oral prednisone therapy (or equivalent) any time in the 8 weeks prior to Day 1, OR any change in/discontinuation of current oral prednisone dose (or equivalent) anytime within the 2 weeks prior to randomisation
(b) Where prednisone is not the single standard of care medication:
(i) Any addition of a new oral prednisone therapy (or equivalent) any time from 2 weeks prior to signing of the informed consent form through Day 1, OR any change in/discontinuation of current oral prednisone dose
(or equivalent) anytime within 2 weeks prior randomisation
(ii) Any addition of a new dose of any of the following anytime in the 12 weeks prior to signing of the informed consent through Day 1, or change in/discontinuation of current dose anytime in the 8 weeks prior to
signing of the informed consent through Day 1: azathioprine; any antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine); mycophenolate mofetil/mycophenolic acid; oral, SC, or intramuscular
methotrexate; mizoribine
2. Receipt of any of the following:
(a) Azathioprine >200 mg/day
(b) Mycophenolate mofetil >2 g/day or mycophenolic acid >1.44 g/day
(c) Oral, SC, or intramuscular methotrexate >25 mg/week
(d) Mizoribine >150 mg/day
(e) Any change in route of administration of oral, SC, or intramuscular
methotrexate anytime within the 8 weeks prior to signing of the
informed consent through Day 1
3. 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
4. Receipt of epratuzumab or tabalumab =26 weeks prior to signing the ICF, or belimumab <12 weeks prior to signing the ICF
5. Receipt of any of the following:
(a) Intra-articular, intramuscular or IV glucocorticosteroids within 6
weeks prior to Day 1
6. History of, or current diagnosis of, a clinically significant non SLErelated
vasculitis syndrome.
7. Active severe or unstable neuropsychiatric SLE
8. Active severe SLE-driven renal disease
9. Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE and SSc.
10. History of, or current, inflammatory joint or skin disease other than SLE
11. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the 24 weeks prior to signing the ICF
12. 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.
13. Confirmed positive test for hepatitis B or hepatitis C
14. Any severe herpes infection at any time prior to Week 0 (Day 1)
15. Opportunistic infection requiring hospitalisation or intravenous antimicrobial treatment within 3 years prior to randomization
16. History of cancer, apart from:
(a) Squamous or basal cell carcinoma of the skin treated with documented success
(b) Cervical cancer in situ that has been successfully treated
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method