Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus
Condition: Active Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Anifrolumab; Placebo
Intervention description: Anifrolumab IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses; Placebo IV administration every 4 weeks from Week 0 to Week 152 for a total of 39 doses
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 559.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Lupus Erythematosus, Systemic Autoimmune Diseases, Connective Tissue Diseases,Immune System Diseases

Summary:

      The purpose of this study is to characterise long-term safety and tolerability of intravenous
      anifrolumab.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects who have qualified for and received investigational product (anifrolumab or
             placebo) and completed the treatment period in Studies D3461C00004 or D3461C00005
             (through Week 52)

          2. Adequate peripheral venous access

          3. Females with an intact cervix should have documentation of a Pap smear with no
             documented malignancy within 90 days before Day 1/Visit 1 or 30 days following Day
             1/Visit 1. Since access to a Pap smear may vary by country, the Sponsor recommends
             that local guidelines for obtaining Pap smears in subjects who have received
             immunomodulators or immunosuppressive treatment be followed.

          4. Meets the following TB criteria:

               1. Negative QuantiFERON®-TB Gold [QFT-G] test result for TB obtained from the study
                  central laboratory at Week 52 of Studies D3461C00004 or D3461C00005; OR

               2. Newly positive QFT-G test result at Week 52 of Studies D3461C00004 or D3461C00005
                  from the study central laboratory. A chest x-ray must be performed. If the chest
                  x-ray shows no evidence of active TB, and the subject has no symptoms or medical
                  history consistent with active TB, the subject must have a retest. If the retest
                  is positive, the subject must start on prophylaxis within 30 days of
                  randomisation but prior to the second dose of investigational product (Visit
                  2/Week 4); OR

               3. Positive but not newly positive QFT-G test at Week 52 of Studies D3461C00004 or
                  D3461C00005. The subject must have been diagnosed with latent TB and must have
                  documentation confirming initiation of appropriate treatment OR initiate
                  treatment for latent TB within 30 days of randomization, but prior to the second
                  dose of investigational product administration (Visit 2/Week 4)

               4. Newly indeterminate (confirmed on retest unless prior positive QFT G was
                  documented, along with completed treatment for latent TB) or indeterminate but
                  not newly indeterminate QFT-G test result at Week 52 of Studies D3461C00004 or
                  D3461C00005 from the study central laboratory with ongoing QFT-G testing for TB
                  according to the Study Plan

          5. In the opinion of the Investigator, subject must be able to comprehend the ICF and all
             protocol related assessments

        Exclusion Criteria:

          1. Receipt of any of the following within the last 60 days:

               1. Azathioprine >200 mg/day

               2. Mycophenolate mofetil >2.0 g/day /mycophenolic acid >1.44 g/day

               3. Oral, subcutaneous, or intramuscular methotrexate >25 mg/week

               4. Mizoribine >150 mg/day

          2. Receipt of any investigational product (small molecule or biologic agent other than
             anifrolumab) within 4 weeks or 5 half-lives prior to Day 1/Visit 1, whichever is
             greater

          3. Receipt of any of the following:

               1. Any live or attenuated vaccine within 8 weeks prior to Day 1/Visit 1
                  (administration of killed vaccines is acceptable, the Sponsor recommends
                  Investigators ensure all subjects are up to date on required vaccinations,
                  including influenza [inactivated/recombinant] vaccine prior to study entry)

               2. Bacillus Calmette-Guerin (BCG) vaccine between the end of Studies D3461C00004 or
                  D3461C00005 and Day 1/Visit 1

          4. Active severe SLE-driven renal or neuropsychiatric disease

          5. Any underlying condition that predisposes the subject to infection, including history
             of/current human immunodeficiency virus (HIV) infection

          6. Subjects with Hepatitis B core antibody (HBcAb) positivity at enrolment of Studies
             D3461C00004 or D3461C00005 will be tested every 3 months for Hepatitis B virus (HBV)
             DNA. To remain eligible in the LTE study, subject HBV DNA levels must remain below the
             lower limit of quantitation as per the central laboratory.

          7. Opportunistic infection requiring hospitalisation or parenteral antimicrobial
             treatment within 3 years of Day 1/Visit 1