Systemic Lupus Erythematosus MedDRA version: 20.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Anifrolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Anifrolumab
CAS Number: 1326232-46-5
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 diagnose
Exclusion criteria
Exclusion criteria: 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 parentertal corticosteroids for more than 2 weeks within the 24 weeksprior 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the effect of anifrolumab 300 mg 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 ; Secondary Objective: 1. To evaluate the effect of anifrolumab 300mg compared to placebo on: a. The proportion of subjects with SRI(4) at Week 52 in the IFN testhigh sub-group b. 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 c. 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 d. The proportion of subjects with SRI(4) at Week 24 e. The annualised flare rate through 52 weeks 2. To evaluate the effect of anifrolumab 150 mg compared to placebo on disease activity as measured by the difference in the proportion of subjects who achieve SRI(4) at Week 52 3. To evaluate the safety and tolerability of anifrolumab ; Primary end point(s): The primary endpoint is the difference in proportions of subjects achieving Systemic Lupus Erythematosus Responder Index SRI(4) at Week 52 comparing anifrolumab to placebo. ;Timepoint(s) of evaluation of this end point: Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1a. The composite endpoint SRI4 will be the measure of this objective. 1b. 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 1c. 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 1d. The composite endpoint SRI4 will be the measure of this objective 1e. 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 2. The composite endpoint SRI4 will be the measure of this objective 3. The following safety data will be collected: vital signs, physical examination, 12-lead ECG, haematology, clinical chemistry, urinalysis, CSSRS, PHQ-8, SLEDAI 2K Flare Index, and reported AEs ; Timepoint(s) of evaluation of this end point: 1a. - Week 52 1b. - Week 52 1c. - Week 12 1d. - Week 24 1e. - Weeks 0- 52 2. - Week 52 3. - Weeks 0-52 | — |
Countries
Argentina, Australia, Brazil, Chile, Colombia, Germany, Hungary, Israel, Italy, Korea, Republic of, New Zealand, Peru, Poland, Romania, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Transparency
AstraZeneca AB
Outcome results
None listed